Thanks for visiting The use of software that blocks ads hinders our ability to serve you the content you came here to enjoy We ask that you consider turning off your ad blocker so we can deliver you the best experience possible while you are here Match Recap: Men's Tennis | 3/16/2025 6:31:00 PM | Evan Snyder / MTSU Athletic Communications Thanks for visiting Match Recap: Men's Tennis | 3/7/2025 9:53:00 PM | Gracie Cunningham UC Santa Barbara Athletic Communications Assistant Thanks for visiting This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page The 5-year old Freiherr Peter and the 6-year old Visser's Hit Valeria VEC  became the winners of the rather small Bundeschampionate qualification classes held at the dressage show in Vöhl on Sunday 30 April 2023 Seven 5-year olds competed in the L-level dressage horse test but no horses obtained a high enough score to clinch a ticket to Warendorf The winner of the class was Mareike Mimberg-Hess aboard Peter Kremer's home bred Westfalian gelding Freiherr Peter (by Furstenball x Sandro Hit) The pair topped the board with a total of 7.60 aboard Bianka Schulte-Krist's Westfalian gelding Di Nozzo (by Dantano x L'Espoir) In the 6-year old division five pairs battled it out and one combination scored enough to make it to Warendorf: the winner of the class Nicole Grosch aced the M-level dressage horse test aboard Sven Hecht's Oldenburg mare Visser's Hit Valeria VEC (by Vitalis x Diamond Hit) They received a winning 8.40 points from judges Ute Kombächer Two pairs tied in second place on a score of 7.50 pounts: Björn Steigauf on Jillian Wyrobnik's DSP stallion Floriano (by Floriscount x Alabster) and Hanna Rüther aboard Stephanie Schnettler's Oldenburg gelding Bugatti Gold (by Best of Gold x Sandro Hit) Stalls for Rent at Durondeau Dressage in Peer, Belgium Exceptionally Well Located Equestrian Facility in Wellington, Florida Well-built Equestrian Estate With Multiple Business Opportunities in Sweden Stable Units for Rent at Lotje Schoots' Equestrian Center in Houten (NED) For Rent: Several Apartments and Stable Wing at High-End Equestrian Facility Stable Wing Available at Reiterhof Wensing on Dutch/German border Real Estate: Well-Appointed Country House with Extensive Equestrian Facility in the U.K. Rémi Blot A community bulletin board for Western Pierce County · March 21 My first encounters with Americans as an adult usually started with them trying out the few German words they knew on me and to run into them when going out was a given was that one of their first German terms they used on me often was “Jawohl”(pronounce: yah-‘vohl) or “Jawoll” (pronounce: yah-‘voll) why did they reply in a way as if I were outranking them in a military hierarchy The answer is simple – watch any older movie about Third Reich Germany (I don’t think there are any about the German Empire) and at one point or another you’ll find the caricature of a German soldier saluting his commander with “Jawoll” or “Jawohl” I never thought this was a Germanism in the English language I rather always thought it a bad JOKE because the Third Reich and its militarism AREN’T a joke to Germans Being answered “Jawohl” or “Jawoll” feels a little like being needled about a nation’s past that is more than shameful I’m not sure whether the German military still uses this word as a reply to the order of another military member It is more of a passive term in the civilians’ vocabulary “nein” can also express an implicit prohibition or an exclamation of surprise whereas “ja” can be used as cheering somebody on There is one variant of the German “ja” that expresses a sigh – it’s “jaja” It expresses either nostalgia when muttered more to oneself Or boredom and irritation when replied to somebody else’s utterance Which is why I end this article here and now before you yawn at me DISCLAIMER: The above news, information, and opinions are the author’s own. If you have news, information or an opinion you’d like to share with 50,000+ monthly readers, click here to learn how FREE EMAIL SUBSCRIPTION: Join 50,000+ readers each month and get the latest news and information from Western Pierce County direct to your inbox, daily, free of charge. Sign up here COMMENT POLICY: If you care to comment on the above story/announcement, feel free. Review our comment policy and please I look forward to reading your posts in the Suburban Times You present a rich knowledge of your German ancestry in the culture and stories and find humor in the way you do that I know I have met you at some occasion(s) in Steilacoom You start off my daily network activities in an uplifting way Copyright © 2025 · The Suburban Times · Log in “How do you feel?” Her wind-chime words are meant for the many men who died in this bedroom almost 150 years ago, in pain. Dion, deeper-pitched, speaks with authority. “If you want to talk to us, go to that light.” The pinprick-sized glow, red like fresh blood, comes from a plastic box on the 19th-century oak floor. It’s a combination motion sensor and electromagnetic field (EMF) detector. We sit in a circle around the machine and wait for it to screech, which would indicate motion, possibly of the paranormal sort. Or perhaps a surge in the surrounding electromagnetic field will make the needle thwap across the screen like a smack in the face. This may represent a ghost (or, I remind myself, a m… Subscribe to Narratively to keep reading this post and get 7 days of free access to the full post archives. Illustrations by Julia Vohl\u201CIs anybody here?\u201D Silence \u201CWe\u2019d love to talk with you.\u201D Silence \u201CCan you make a sound for us?\u201D Diane\u2019s voice creeps upward through the blackness with a tinge of desperation \u201CHow do you feel?\u201D Her wind-chime words are meant for the many men who died in this bedroom almost 150 years ago go to that light.\u201D The pinprick-sized glow comes from a plastic box on the 19th-century oak floor It\u2019s a combination motion sensor and electromagnetic field (EMF) detector We sit in a circle around the machine and wait for it to screech Or perhaps a surge in the surrounding electromagnetic field will make the needle thwap across the screen like a smack in the face You may not be able to find the page you were after because of: You might find one of the following links useful: Robotic microscopes revolutionize biological research by automating cell tracking and enabling longitudinal studies on diseases Consumer drones are reshaping how we think about privacy blurring the lines between public airspace and personal space Feedback systems are crucial for robotic autonomy enabling real-time adaptation and decision-making for safe and efficient operation in various environments Discover Cavitar’s welding cameras that can be used in a variety of situations to offer high-quality visualization of the welding processes MTI’s 1510A portable signal generator and calibrator is ideal for testing the integrity of sensor signal conditioning electronics Using the advantages of the phased array technology Olympus has designed a powerful inspection system for seamless pipe inspections well-adapted to the stringent requirements of the oil and gas markets This phased array system is flexible and can be used to match inspection performances and the product requirements of customers you can trust me to find commercial scientific answers from AZoNetwork.com please log into your AZoProfile account first Registered members can chat with Azthena, request quotations, download pdf's, brochures and subscribe to our related newsletter content A few things you need to know before we start Read the full Terms & Conditions. Owned and operated by AZoNetwork, © 2000-2025 SearchSearchWednesday 6at1Tulane Photo by: Ken ShepherdMen's Tennis Defeats Tulane 6-11/29/2025 8:17:00 PM | Men's Tennis Metrics details NADH oxidation is coupled to ion translocation across the membrane to build up an electrochemical gradient the sodium-pumping NADH:quinone oxidoreductase (Na+-NQR) generates a sodium gradient by a so far unknown mechanism Here we show that ion pumping in Na+-NQR is driven by large conformational changes coupling electron transfer to ion translocation We have determined a series of cryo-EM and X-ray structures of the Na+-NQR that represent snapshots of the catalytic cycle and F of Na+-NQR harbor a unique set of cofactors that shuttle the electrons from NADH twice across the membrane to quinone The redox state of a unique intramembranous [2Fe-2S] cluster orchestrates the movements of subunit NqrC We propose that this switching movement controls the release of Na+ from a binding site localized in subunit NqrB and the positions of side chains and the cofactor riboflavin were not unambiguously resolved The high-resolution cryo-EM structures reported here reveal the exact localization and nature of all cofactors including a [2Fe-2S] cluster in subunits NqrD and NqrE Overall structure of Na+-NQR in complex with NADH and ubiquinone-2 Structure of Na+-NQR determined by X-ray crystallography Both structures differ in the position of the periplasmic hydrophilic domain of NqrC Structural overlay of the cryo-EM (red) and X-ray (gray) structures of NqrF bound to NADH and UQ-2 NqrD (magenta) and NqrE (cyan) are shown as surface the FNR-like domain of NqrF is shifted sideways and the ferredoxin (Fdxn)-like domain is rotated towards the membrane subunits in the cryo-EM structure Edge-to-edge distances of redox cofactors in Na+-NQR determined by cryo-EM Edge-to-edge distances of redox cofactors in Na+-NQR determined by X-ray crystallography Gray bars indicate the location of the membrane Close-up view of subunits NqrD-E coordinating a [2Fe-2S] cluster with cysteines originating from both subunits Localization of the [2Fe-2S] clusters in cytoplasmic NqrF and in membrane subunits NqrD-E The blue circle indicates the [2Fe-2S]NqrF cluster; the red circle indicates the [2Fe-2S]NqrD-E cluster CD spectra of wild-type (WT) Na+-NQR; NqrF-C70A which is devoid of [2Fe-2S]NqrF; and NqrD-C29A the [2Fe-2S]NqrD-E cluster (red trace) in NqrF-C70A and the [2Fe-2S]NqrF cluster (blue trace) in NqrD-C29A are shown k3-weighted EXAFS and Fourier transform spectra of cluster [2Fe-2S]NqrD-E (red) in NqrF-C70A and cluster [2Fe-2S]NqrF (blue) in NqrD-C29A 57Fe Mössbauer spectrum of the [2Fe-2S]NqrD-E cluster in NqrF-C70A 10 K X-band EPR spectrum of Na+-NQR variant NqrF-C70A showing [2Fe-2S]NqrD-E cluster simulated with two components: a [2Fe-2S] cluster (orange; g|| = 2.02 line width = 50 G) and a radical signal (purple; giso = 2.01 cholerae expressing WT Na+-NQR (black) or Na+-NQR variants containing cluster [2Fe-2S]NqrD-E (red) in variant NqrF-C70A or cluster [2Fe-2S]NqrF (blue) in variant NqrD-C29A Source data Structural alignment of Na+-NQR in two states highlighting the two conformations of NqrC trapped in cryo-EM and X-ray structures The membrane plane is indicated by gray bars The movement of NqrC corresponds to a 26-degree rotation of the hydrophilic domain green spheres) binds to the rim of NqrB with the head group close to the cytoplasmic aspect of the membrane Interactions of UQ-1 (b) and UQ-2 (c) with NqrB The isoprenoid and the methyl group are in hydrophobic contact with residues F159 whereas the O4 can form a hydrogen bond to a backbone carbonyl of N156 Replacement of G141 with any other amino acid residue would sterically block the interaction of quinones with NqrB at the N terminus of NqrB close upon UQ binding and contribute to the mainly hydrophobic interaction of UQ-1 or UQ-2 with NqrB The methoxy groups of the quinone head group are in hydrophobic contact with the side chains of L26 These interactions are critical and stabilize the bound cofactor in this position in an induced-fit binding mode Structural alignment of Na+-NQR in complex with either UQ-1 or with HQNO The binding sites for both molecules overlap but head groups and tails localize in different regions of the binding site The quinolone head group of HQNO interacts with the side chain of F160 and L33 The alkyl chain of HQNO covers the space of the head group of quinones and follows the course of the isoprenoid tail HQNO recruits the N-terminal amphiphilic helices to form a high-affinity binding site cholerae is replaced by a phenylalanine in NqrB of P aeruginosa that predicts that HQNO binding is indeed hampered by the bulky side chain of phenylalanine This strongly suggests that the different conformation of NqrC in the X-ray structure is due to the crystallization of Na+-NQR The conformational change is not due to pH or ionic strength of the crystallization conditions because these are similar to the buffer conditions used for the cryo-EM samples We concluded that the packing of the Na+-NQR in the crystal provides enough energy to stabilize NqrC in its position at NqrD-E the subunit arrangement observed in the X-ray structure is largely stabilized by the packing of the molecules in the crystal NqrC interacts in the crystal with two neighboring Na+-NQR molecules forming three salt bridges and several hydrogen bonds thus stabilizing a conformation that represents a certain state of the catalytic cycle Because this state is not observed at thermodynamic equilibrium it is most likely a transient or metastable state that is trapped by the crystal packing The close proximity of FMNNqrC to [2Fe-2S]NqrD-E suggests that it represents a snapshot of transmembrane electron transfer as shown by experiments treating the protein in the crystals with the inhibitor DQA incubation of the crystals with the inhibitor triggered a large conformational change of NqrC NqrC does not reach the final relaxed position at NqrB that was observed in the cryo-EM structures and some residual crystal contacts capture Na+-NQR in a transient state we can distinguish three conformations of Na+-NQR that reflect different states: (1) the relaxed state as observed in the cryo-EM structures; (2) a short-lived transmembrane electron-transfer state that is shown in the X-ray structure of Na+-NQR; and (3) an intermediate state between these two states obtained after treatment of the crystals with DQA A systematic analysis of the structures revealed that the states differ not just in the position of NqrC, but also in the conformation of NqrD-E and in the position and interhelical angles of the transmembrane helices of NqrC and NqrF (Extended Data Fig. 8) showing that the various movements of the different subunits are tightly interconnected Helix-III and the half-helix-IV of NqrE tilt and move by 6–10 Å NqrD and NqrE are related by an inverted topology and form a compact dimer any conformational changes in one of these subunits will affect the other NqrD and NqrE are tightly coupled to each other: conformational changes of helix-III and half-helix-IV of NqrE are linked to conformational changes of helix-III and half-helix-IV of NqrD in the opposite direction This additional negative charge might attract the positive dipole of one half-helix and repulse the negative dipole of the second half-helix promoting the reorientation of the helices Two ion-binding sites were identified in NqrB Both sites are located close to the periplasmic aspect of NqrB and the Na+ ion is coordinated by three backbone carbonyl oxygen atoms and two water molecules with a coordination sphere of four backbone carbonyl oxygens and one water molecule A Na+-translocation pathway through NqrB is predicted The translocation pathway is constricted close to residues F338 and F342 The results corroborate that F338 and F342 in NqrB are critically involved in Na+ translocation given suitable distances between the redox cofactors electron transfer is several orders of magnitudes faster than ion translocation If all six redox cofactors would reside in short distance from each other suited for fast electron transfer the ion-translocation process would be too slow to be connected to several electron-transfer steps; that is the energy of the different redox steps would deflagrate To couple electron transfer to the Na+-pumping process the system has to decelerate electron transfer at certain steps to allow ion translocation to proceed Such slow phases are intimately linked to states of Na+-NQR in which we observe large distances between the redox centers; that is the distance between the redox centers has to increase conformational changes will again move redox centers within the electron-transfer distance for fast electron transfer The catalytic cycle starts with NADH becoming oxidized at NqrF Electrons are transferred to the flexibly tethered ferredoxin-like domain of NqrF A Na+ is bound in NqrB close to the periplasmic half-channel but the release of the ion is blocked by NqrC NqrD-E adopt a conformation that allows access of the intramembranous [2Fe-2S]NqrD-E cluster from the cytoplasmic side whereas access for NqrC at the periplasmic side is blocked The ferredoxin-like domain of NqrF can reach the [2Fe-2S]NqrD-E cluster and transfers an electron This electron transfer prepares for binding of a Na+ to the cytoplasmic half-channel in NqrB The reduction of [2Fe-2S]NqrD-E triggers a conformational switch in subunits NqrD-E now obstructing the access of [2Fe-2S]NqrD-E at the cytoplasmic side but facilitating access of NqrC at the periplasmic side NqrC rotates from its position at NqrB towards NqrD-E and triggers the release of the Na+ bound at the periplasmic side in proximity of FMNNqrB The conformational change of NqrC locates FMNNqrC close to [2Fe-2S]NqrD-E resulting in fast electron transfer to the flavin Oxidation of the [2Fe-2S]NqrD-E cluster will switch NqrD-E back to its previous conformation the electron is transferred rapidly to FMNNqrB It is proposed that the reduced FMNNqrB triggers a transient opening between both half-channels in NqrB enabling translocation of the Na+ to the periplasmic half-channel NqrB is reoxidized by electron transfer to riboflavinNqrB and subsequently to ubiquinone Our results provide a detailed model of dynamic conformational coupling of electron transfer to Na+ translocation in Na+-NQR of the human pathogen V This exemplifies how redox energy is converted into a chemiosmotic gradient by a respiratory complex Na+-NQR is crucial for energy conservation in a plethora of Gram-negative pathogenic bacteria including multidrug-resistant species like Klebsiella spp The structural information on HQNO binding forms an excellent basis for the development of new antibiotics hexahistidine-tagged Na+-NQR was expressed in V Membranes were isolated and solubilized with n-dodecyl-β-d-maltoside (DDM; Glycon) Na+-NQR was purified via Ni-Sepharose Fast Flow (Cytiva) utilizing the N-terminal hexahistidine tag fused to subunit NqrA Purified Na+-NQR was dialyzed against 50 mM sodium phosphate Na+-NQR was concentrated by ultrafiltration (Amicon 100-kDa cut-off) and further purified by size-exclusion chromatography using a Superdex 200 (16/60) column (GE Healthcare) equilibrated in 50 mM HEPES-NaOH the hexahistidine tag was removed from NqrA by proteolysis with HRV-3C protease carrying a hexahistidine tag on ice prior to gel filtration The digest was supplemented with 0.25 μM phenylmethylsulfonyl fluoride and passed again over Ni-Sepharose Fast Flow (Cytiva) in order to remove undigested protein Na+-NQR (wild-type or variants) was purified as described above Na+-NQR in buffer (50 mM potassium phosphate 5 % glycerol) was flash-frozen in liquid N2 and stored at −80 °C until use the Na+-NQR complex was prepared at a concentration of 1 mg ml–1 in 10 mM HEPES pH 8.0 Fifty-microliter aliquots (50 µg protein) were used for the experiments Na+-NQR was cross-linked in the absence and presence of the inhibitor DQA DQA was added from a 50 mM stock in DMSO to a final concentration of 0.5 mM Samples were incubated for 45 min at room temperature before cross-linking Cross-linking was performed using a mixture of isotopically light (d0) and heavy (d12) di(succinimidyl)suberate (DSS-d0/d12 DSS was added to a final concentration of 1 mM from a 25 mM stock solution prepared in DMF and samples were incubated for 45 min at 25 °C ammonium bicarbonate was added to a final concentration of 50 mM from a 1 M stock solution prepared in water and samples were incubated for another 20 min For reduction and alkylation of cysteine residues tris(2-carboxyethyl)phosphine (50 mM in water) was added to a final concentration of 5 mM and the sample was incubated for 30 min at 37 °C iodoacetamide (100 mM in water) was added to a final concentration of 10 mM and samples were incubated at room temperature for 30 min in the dark This step was followed by the addition of 0.5 µg endoproteinase Lys-C (Wako and digestion was allowed to proceed for 2.5 h at 37 °C Sample solutions were diluted to a final volume of 400 µl with 50 mM ammonium bicarbonate (which diluted DDM below the CMC) Three fractions corresponding to the predominant elution range of cross-linked peptides were collected separately for mass spectrometry and were evaporated to dryness Dried SEC fractions were dissolved in 20 µl of water/acetonitrile/formic acid (95/5/0.1 and 4 µl was analyzed in duplicate on a liquid chromatography–mass spectrometry system consisting of an Easy nLC-1200 HPLC system and an Orbitrap Fusion Lumos mass spectrometer (both Thermo Fisher Scientific) Peptides were separated on an Acclaim PepMap RSLC C18 column (25 cm × 75 µm Thermo Fisher Scientific) at a flow rate of 300 nl min–1 and with a gradient of 89% mobile phase A/11% mobile phase B to 60% A/40% B in 60 min where A is water/acetonitrile/formic acid (98/2/0.15 vol/vol/vol) and B is acetonitrile/water/formic acid (80/20/0.15 Peptides were sequenced in the data-dependent acquisition mode with precursor ion scans acquired in the orbitrap analyzer at a resolution of 120,000 The most abundant precursors with a charge state of +3 or higher were selected for sequencing by collision-induced dissociation in the linear ion trap at a normalized collision energy of 35% and fragment ions were detected in the linear ion trap at rapid speed The cycle time for sequencing was set to 3 s and dynamic exclusion was enabled after one sequencing event for 30 s DSS specificity was set to only lysine residues Mass error tolerances for the xQuest search were set to ± 15 ppm at the MS1 level and to 0.2 Da and 0.3 Da (for common and xlink ion types Relative changes in the abundance of cross-linked peptide pairs are given as +DQA/–DQA ratios Ratios were median-normalized and averaged over charge states and were determined for light and heavy DSS products The amino acid sequence of NqrF from V. cholerae (residues 129–408) representing the FNR-like NADH-oxidizing domain2 was obtained from Uniprot (ID: A5F5Y4) An N-terminal 6×His-tag and a subsequent HRV-3C cleavage site were added and codons were optimized for expression in Escherichia coli Genes coding for NqrF129-408 and NqrF129-408-F406A were synthesized by GeneArt (Thermo Fisher Scientific) and cloned into vector pET15b via flanking 5′ NcoI and 3′ BamHI replacing the 6×His-tag and thrombin-cleavage site of pET15b coli Tuner (DE3) strain was transformed with plasmid pFNF53 or pFNF406A Cells were grown in DYT medium containing 100 µg ml−1 ampicillin at 37 °C Expression of the FAD domain was induced with 1 mM IPTG at an OD600 of 0.9 Cells were collected after 5 h at 30 °C and washed in 10 mM Tris-HCl Cells were broken by one passage through an Emulsiflex C-3 cell disruptor (Avestin) at approximately 20 kpsi in the presence of 1 mM DTT and protease inhibitors (complete EDTA-free Cell debris was removed by centrifugation at 20,000g for 20 min After ultracentrifugation of the cellular extract at 150,000g (Beckman Type 70Ti) the supernatant was filtrated and loaded onto a Ni Sepharose HP column (5 ml bed volume Cytiva) equilibrated with buffer A (20 mM Tris-HCl The column was washed with 5 volumes of buffer A containing 30 mM imidazole and histidine-tagged protein was eluted with 400 mM imidazole in buffer A Peak fractions were combined and diluted at least 1:10 in 50 mM HEPES-NaOH The histidine tag was cleaved off by incubation for 15 h at 4 °C with PreScission protease By loading the digest onto the Ni+ column and washing with 50 mM HEPES-NaOH FAD domain devoid of the histidine tag was obtained The protein was loaded onto a SourceQ column (10 ml bed volume Cytiva) equilibrated with 50 mM HEPES-NaOH and was eluted with a linear gradient from 0 to 0.4 M NaCl and proteins were frozen in liquid nitrogen Point mutations were introduced into plasmid pNqr1 by a single PCR reaction (KAPAHiFi PCR Kit Peqlab) with the corresponding forward and reverse primers Mutated codons that introduce the altered amino acid residues in the Nqr subunits are underlined Plasmid pNF-C70A codes for Na+-NQR carrying the p.C70A substitution in NqrF 5′-GTATTCGTATCTTCAGCTGCGGGTGGTGGTGGTTCATGTGG-3′ and 5′-CCACATGAACCACCACCACCCGCAGCTGAAGATACG-3′ Plasmid pND-C29A codes for Na+-NQR carrying the p.C29A substitution in NqrD The forward and reverse primers were 5′-TTCTGGGTGTGGCGCTGCACTGGC-3′ and 5′-CCAGTGCAGACGCCACACCCAGAAC-3′ Plasmid pNDE-C29A-C120A codes for Na+-NQR carrying the p.C29A substitution in NqrD and the p.C120A substitution in NqrE Substitution p.C29A was inserted with the same forward and reverse primers like in pND-C29A the forward and reverse primers were 5′-GATCACAGTAAACGCGGCGATCTTCGG-3′ and 5′-GAAGATCGCCGCGTTTACTGTGATCAGC-3′ Plasmid pNE-C120S codes for Na+-NQR carrying the p.C120S substitution in NqrE The forward and reverse primers were 5′-GATCACAGTAAACTCAGCGATCTTCGGTGG-3′ and 5′-ACCGAAGATCGCTGAGTTTACTGTGATCAGC-3′ The enrichment of 57Fe in Na+-NQR was at least 70% as confirmed by inductively coupled mass spectroscopy A second-order polynomial was fit to the pre-edge region and subtracted throughout the entire EXAFS spectrum A three-region cubic spline (with the AUTOBK function within Athena) was used to model the background function to a minimum of k = 13.5 Å−1 for all spectra Fourier transforms were performed over a windowed k range of 2.0–13.0 Å−1 and all FT spectra are presented without a phase-shift correction Spectra were collected in a dual-mode X-band resonator operated in perpendicular-mode (TE102) Magnetic circular dichroism spectra of Na+-NQR (10–20 mg ml−1) were recorded on a Jasco J-715 magnetic circular dichroism (MCD) spectrometer equipped with a permanent 1.6 T magnet Measurements were performed at room temperature using a 2 mm quartz cuvette at a speed of 100 nm min−1 A magnetic field was applied and –MCD and +MCD spectra were recorded These spectra were used to calculate CD spectra using the formula: +MCD + –MCD = 2 CD UV-visible spectra were recorded on a Lambda 12 UV/VIS spectrophotometer (Perkin Elmer) at 19 °C Absorbance of Na+-NQR (50–100 µM) after gel filtration in 10 mM HEPES pH 8.0 and 0.05% DDM was measured in a 1 mm quartz cuvette Point mutations were introduced into plasmid pNqr1 by a single PCR reaction (KAPAHiFiTM PCR Kit from Peqlab) with the corresponding forward and reverse primers Plasmid pNF-D346A codes for Na+-NQR carrying the p.D346A substitution in NqrB The forward and reverse primers were 5′-GTTCTTCATGGCGACTGCGCCAGTTTCTGCGTC-3′ and 5′-GAAGGACGCAGAAACTGGCGCAGTCGCCATGAAG-3′ Plasmid pNB_F342A codes for Na+-NQR carrying the p.F342A substitution in NqrB The forward and reverse primers were 5′-CGCATTCGGTATGTTCGCTATGGCGACTGACCC-3′ and 5′-GAAACTGGGTCAGTCGCCATAGCGAACATACCG-3′ Bandelin) in a 1.5-mL reaction tube on ice The tip was placed 1 cm below the surface of the proteoliposome suspension with cooling times of 60 s between the pulses To decrease the detergent concentration below the critical micellar concentration (CMC) the suspension was diluted with a 50-fold volume of reconstitution buffer using a burette (30 drops min−1) the pellet containing the proteoliposomes was suspended in 1 ml reconstitution buffer per 1 mg Na+-NQR corresponding to 2 ml reconstitution buffer per 40 mg l-α-phosphatidylcholine proteoliposomes (0.16 mg Na+-NQR in 3.2 mg lipids) were mixed with 6 µM oxonol VI which was identical to the reconstitution buffer the reaction was started by the addition of 0.2 mM NADH (dipotassium salt) and voltage formation was followed at 25 °C under stirring Typical traces from three replicates are presented Vectors were created to express Na+-NQR variants carrying cysteine substitutions Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article regulation and function of the mitochondrial respiratory chain cholerae Na+-pumping NADH:quinone oxidoreductase The Na+/e− stoichiometry of the Na+-motive NADH: quinone oxidoreductase in Vibrio alginolyticus Cryo-EM structures of Na+-pumping NADH-ubiquinone oxidoreductase from Vibrio cholerae Identification and evolution of dual-topology membrane proteins Analysis of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines (HAQs) reveals a role for 4-hydroxy-2-heptylquinoline in cell-to-cell communication Characterization of the Pseudomonas aeruginosa NQR complex a bacterial proton pump with roles in autopoisoning resistance Incorporating protein environments in density functional theory: a self-consistent reaction field calculation of redox potentials of [2Fe2S] clusters in ferredoxin and phthalate dioxygenase reductase Acid residues in the transmembrane helices of the Na+-pumping NADH:quinone oxidoreductase from Vibrio cholerae involved in sodium translocation Structure and permeation mechanism of a mammalian urea transporter Mechanism of ammonia transport by Amt/MEP/Rh: structure of AmtB at 1.35 Å Crystal structure of the archaeal ammonium transporter Amt-1 from Archaeoglobus fulgidus Metal–ligand geometry relevant to proteins and in proteins: sodium and potassium Validation of metal-binding sites in macromolecular structures with the CheckMyMetal web server The role and specificity of the catalytic and regulatory cation-binding sites of the Na+-pumping NADH:quinone oxidoreductase from Vibrio cholerae Strong pH dependence of coupling efficiency of the Na+-translocating NADH:quinone oxidoreductase (Na+-NQR) of Vibrio cholerae HOLE: a program for the analysis of the pore dimensions of ion channel structural models Transport and pharmacological properties of nine different human Na,K-ATPase isozymes Mechanism of the rate-determining step of the Na +,K + -ATPase pump cycle Role of the Na+-translocating NADH:quinone oxidoreductase in voltage generation and Na+ extrusion in Vibrio cholerae Purification and structural characterization of the Na+-translocating ferredoxin: NAD+ reductase (Rnf) complex of Clostridium tetanomorphum Oxidant-induced formation of a neutral flavosemiquinone in the Na+-translocating NADH:quinone oxidoreductase (Na+-NQR) from Vibrio cholerae Purification and characterization of the recombinant Na+-translocating NADH:quinone oxidoreductase from Vibrio cholerae Crystallization of the Na+-translocating NADH:quinone oxidoreductase from Vibrio cholerae DA+ data acquisition and analysis software at the Swiss Light Source macromolecular crystallography beamlines MxCuBE: a synchrotron beamline control environment customized for macromolecular crystallography experiments ANODE: anomalous and heavy-atom density calculation REFMAC 5 for the refinement of macromolecular crystal structures Automatic multiple-zone rigid-body refinement with a large convergence radius AceDRG: a stereochemical description generator for ligands General atomic and molecular electronic structure system Real-space refinement in PHENIX for cryo-EM and crystallography Electronic ligand builder and optimization workbench (eLBOW): a tool for ligand coordinate and restraint generation New tools for automated cryo-EM single-particle analysis in RELION-4.0 RELION: implementation of a Bayesian approach to cryo-EM structure determination MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy CTFFIND4: fast and accurate defocus estimation from electron micrographs Positive-unlabeled convolutional neural networks for particle picking in cryo-electron micrographs Improvement of cryo-EM maps by density modification Highly accurate protein structure prediction with AlphaFold AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models Model-based local density sharpening of cryo-EM maps Valence screening of water in protein crystals reveals potential Na+ binding sites CheckMyMetal: a macromolecular metal-binding validation tool Lysine-specific chemical cross-linking of protein complexes and identification of cross-linking sites using LC-MS/MS and the xQuest/xProphet software pipeline False discovery rate estimation for cross-linked peptides identified by mass spectrometry A cross-platform toolkit for mass spectrometry and proteomics Identification of cross-linked peptides from large sequence databases Empirical scoring functions for advanced protein−ligand docking with PLANTS An ant colony optimization approach to flexible protein–ligand docking Lessons learned in empirical scoring with smina from the CSAR 2011 benchmarking exercise new empirical halogen bond scoring function pK(a) based protonation states and microspecies for protein-ligand docking Growth yield increase linked to caffeate reduction in Acetobacterium woodii Semi-micro methods for analysis of labile sulfide and of labile sulfide plus sulfane sulfur in unusually stable iron-sulfur proteins Design and characterization of phosphine iron hydrides: toward hydrogen-producing catalysts A function minimization computer package (MFIT) for nonlinear parameter estimation providing readily accessible maximum likelihood estimates The five-analyzer point-to-point scanning crystal spectrometer at ESRF ID26 HEPHAESTUS: data analysis for X-ray absorption spectroscopy using IFEFFIT Histidine-gated proton-coupled electron transfer to the Cu A site of nitrous oxide reductase Reconstitution of sodium transport from purified oxaloacetate decarboxylase and phospholipid vesicles Comparison of liposomes formed by sonication and extrusion: rotational and translational diffusion of an embedded chromophore Quinone reduction by the Na+-translocating NADH dehydrogenase promotes extracellular superoxide production in Vibrio cholerae The Na+-translocating NADH:quinone oxidoreductase enhances oxidative stress in the cytoplasm of Vibrio cholerae The single NqrB and NqrC subunits in the Na+-translocating NADH: quinone oxidoreductase (Na+-NQR) from Vibrio cholerae each carry one covalently attached FMN The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences Download references This work was supported by grant 311211092 from the Deutsche Forschungsgemeinschaft (G.F and by fellowships from the Carl-Zeiss-Foundation (B.C.) the Landesgraduiertenförderung Baden-Württemberg (V.M.) Synchrotron data were collected under proposal MX-346 at beamline P14 operated by EMBL Hamburg at the PETRA III storage ring (DESY Germany) and at beamlines X06SA and X06DA at Swiss Light Source of the Paul Scherrer Institute (Villigen We thank the Central Electron Microscopy Facility of the Max Planck Institute of Biophysics for excellent support Yildiz and the Max Planck Computing and Data Facility for maintaining the computational infrastructure for cryo-EM the staff at beamlines X06SA and X06DA at Swiss Light Source The HERFD-XAS experiments were performed on beamline ID-26 at the European Synchrotron Radiation Facility (ESRF) Amidani at ESRF for assistance at beamline ID-26 for access to laboratory infrastructure and instrumentation Open access funding provided by Universität Hohenheim Jann-Louis Hau, Valentin Muras, Marco S Casutt, Georg Vohl, Björn Claußen, Wojtek Steffen, Julia Steuber & Günter Fritz Max Planck Institute for Chemical Energy Conversion performed crystallization and data collection performed XAS experiments and analyzed data performed EPR and Mössbauer experiments and analyzed data prepared cryo-EM samples and performed data collection processed the cryo-EM data and performed model building and refinement The authors declare no competing interests : Nature Structural & Molecular Biology thanks Leonid Sazanov and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editors: Carolina Perdigoto and Katarzyna Ciazynska, in collaboration with the Nature Structural & Molecular Biology team. Peer reviewer reports are available Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Representative micrograph of Na+-NQR with UQ-1 Gold-standard Fourier Shell Correlation curves and maps colored by local resolution (color scale in Å) Source data Several lipids and DDM molecules were well defined by the cryo-EM density The bound lipids and detergent molecules define the extent of membrane indicated here by grey lines DDM detergent molecules are depicted in grey Complex of NADH with NqrF in Na+-NQR cryo-EM structure The C4N of the nicotinamide group of NADH carrying the 2 e− is at a distance of 3.3 Å of N5 of the FAD that is in perfect hydride transfer distance The edge-to-edge distance between the C8M of the FAD and the proximal Fe of the [2Fe−2S] cluster is 9.4 Å The adenine moiety of NADH resides in a separate pocket of the protein whereas the nicotinamide shares a pocket with the isoalloxazine of FAD In contrast to the cryo-EM structure the X-ray structure of isolated NqrF in complex with NADH the nicotinamide is separated from the isoalloxazine by Phe406 and cannot transfer its hydride to N5 of FAD Residue Phe406 has to move out of the binding pocket to promote hydride transfer To address the role of residue Phe406 in NADH binding we determined the X-ray structure of a NqrF variant where Phe406 is replaced by Ala In contrast to wildtype NqrF the NqrF Phe406Ala variant exhibited productive binding of the nicotinamide moiety of NADH in close proximity to the FAD The structure revealed that the nicotinamide binds close to the isoalloxazine The C4N of the nicotinamide group of NADH is in a distance of 3.5 Å of N5 of the FAD X-ray structure of NqrF subunit in complex with NADH shown in a similar orientation like in c The 2fo-fc at 1.5 σ around bound NADH is shown The hydrophilic domain of NqrC moves between two positions at either NqrB or NqrD-E shuttling the electrons from the intramembranous [2Fe−2S] in NqrD-E to NqrB The cryo-EM structures and the X-ray structures represent snapshots of these switching movement of NqrC NqrB and NqrD which are predicted to form disulphide bonds in either state The cysteine residues are located in the periplasm that with its oxidizing environment facilitates disulphide bond formation Variants of Na+-NQR with corresponding cysteine residues were isolated and analysed by non-reducing SDS-PAGE Both variants corresponding to both states of NqrC form disulphide bonds as indicated by the shift of bands to higher molecular mass The covalent FMN containing subunits NqrC and NqrB were monitored by their fluorescence at 508 nm The disulphide crosslink of NqrC with NqrB and with NqrD demonstrates that both conformations occur in vivo Both variants showed diminished ratios of UQ-1/NADH reduction rates showing that the electron transfer through Na+-NQR is impaired Reduction of the disulphide bonds restores the electron transfer to UQ-1 as shown by an approximate 2-fold increase of the UQ-1/NADH ratios Kinetic data are shown as mean ± SD including error propagation Individual data points are shown as open spheres Two-sided paired sample t test was applied with confidence interval = 0.95 and degree of freedom =6 5.71 10−5 for variant NqrC-P174C-NqrD-Q100C and 0.003 for variant NqrC-L226C-NqrB-P376C Vibrio cholerae strains expressing the variants instead of wt Na+-NQR are drastically impaired in growth displaying slower growth rates and 45% lower cell yields n = 3 biologically independent experiments Source data NqrB (orange) contains a covalent FMN and a riboflavin as cofactors Both flavins are depicted as yellow spheres Detailed view on the location of FMN and riboflavin in NqrB The FMN cofactor is located close to the periplasmic aspect of NqrB the riboflavin closer to the cytoplasmic aspect Interactions of riboflavin with the residues of NqrB Several hydrogen bonds (green dotted lines) are formed with the ribityl sidechain and the isoalloxazine The backbone amide of Gly198 and the sidechains of Asn200 and Asp346 form hydrogen bonds with the oxygen atoms of the ribityl chain The backbone amide and carbonyl of Ala205 and Phe342 as well as the sidechains of Thr162 and Asn203 form hydrogen bonds with N1 Voltage generation by isolated wt Na+-NQR and variant Na+-NQR-NqrB-D346A Voltage generation by the variant is drastically decreased Growth of Vibrio cholerae expressing either wt Na+-NQR (■) or a Na+-NQR variant lacking the entire subunit NqrB (○) Growth rate and growth yield of Na+-NQR-NqrB-346A variant (▲) is diminished Source data UQ-1 is interacting mainly with hydrophobic residues of NqrB One hydrogen bond is formed to the backbone carbonyl oxygen of Asn156 Cryo-EM map around inhibitor HQNO (magenta) HQNO interacts with similar residues like UQ-1 HQNO forms two hydrogens bonds with backbone amide of residues 159 and 160 or NqrB HQNO binds somewhat deeper into NqrB than ubiquinone The residues NqrB155–157 shift by about 1.5 Å creating a slightly larger binding pocket than the ubiquinone HQNO recruits the N-terminal amphiphilic helices to form a high affinity binding site Docking of UQ1 into the structure of Na+-NQR yields a solution that is reasonable agreement with the modelled UQ-1 Docking of HQNO into the structure of Na+-NQR gives a perfect match of the docking solution and the modelled HQNO that is HQNO is predicted to bind with higher affinity than UQ-1 Cross section through subunits NqrD-E at the position of the [2Fe−2S]NqrD-E (shown as spheres) The cryo-EM structure of NqrD-E in the oxidized state is shown on the left-hand side in dark colors The structure assigned to a reduced [2Fe−2S]NqrD-E cluster is shown on the right-hand side in light colors The distances of the cluster to the membrane planes are indicated the cluster moves almost 2 Å relative to the membrane plane Structural alignment of NqrD-E and of the NqrC The conformational changes are indicated by arrows illustrating how NqrD-E opens in the oxidized state (dark colors) compared to the reduced state (light colors) Detailed view of structural changes in the region of helices III and IV of NqrD-E The movement of the helices between both states is indicated by arrows NqrD-Arg71 of and NqrE-Glu95 approach each other to form a salt bridge stabilizing the conformation corresponding to the reduced state of the [2Fe-2S]NqrD-E cluster Anomalous difference maps in the region of entire Na+-NQR The map is derived from crystals grown in the presence of CsCl The dataset was recorded at 1.7 Å close to the L-I edge of Cs to maximize the anomalous contribution of these metal ions the [2Fe-2S]NqrD-E and rigidly bound Cs+ will exhibit a strong anomalous signal Strong anomalous difference map peaks (green) are observed at the positions of [2Fe-2S]NqrF [2Fe-2S]NqrD-E and at the periplasmic aspect of NqrB Anomalous difference maps of Na+-NQR derived from crystals grown in the presence of RbCl The dataset was recorded at the K-edge of Rb at 0.82 Å Strong anomalous difference map peaks (red) are observed at the periplasmic aspect of NqrB Some minor peaks deriving from the [2Fe-2S] clusters are observed as well Overlay of the anomalous difference maps deriving from Cs+ (green) and Rb+ (red) bound to Na+-NQR The binding site for both ions maps to site Na-2 close to the interaction site of NqrB with NqrC Na+-dependent NADH oxidation rates of wt Na+-NQR and variants NqrB-F338A and NqrB-F342A The variant exhibits an NADH oxidation rate that is about 5% diminished compared to wt Na+-NQR whereas variant NqrB-F342A shows a 7% higher activity than wt NQR Na+-dependent UQ1 reduction rates reveal almost identical rates for wt Na+-NQR and variant NqrB-F342A while the rate for NqrB-F338A is reduced by about 8% electron transfer activity is only marginally affected in both variants confirming that the structural integrity is not affected by these mutations Voltage generation in proteoliposomes monitored with oxonol is reduced by about 30% for variants NqrB-F338A and NqrB-F342A compared to wt Na+-NQR Residues Phe338 and Phe342 are located at the constriction of the proposed Na+-translocation pathway and might serve as a gate In both variants the bulky Phe residue has been replaced by the smaller Ala This may be explained by a backflow of Na+ during translocation because of an incomplete closure of the gate In control experiments without addition of NADH (dotted trace) Source data Kinetics and coupling of wildtype Na+-NQR and variants with engineered disulfide bonds; growth curves of wildtype Na+-NQR and variants Unprocessed Coomassie-stained gel and flavin fluorescence of gel Voltage generation by wildtype Na+-NQR (wildtype is same as in Extended Data Fig 10) and Na+-NQR variants NqrB-D346A; growth curves of wildtype Na+-NQR and variant NqrB-D346A Kinetic characterization and voltage generation by wildtype Na+-NQR (voltage generation of wildtype is same as in Extended Data Fig 5) and Na+-NQR variants NqrB-F338A and NqrB-F342A Download citation DOI: https://doi.org/10.1038/s41594-023-01099-0 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing newsletter — what matters in science was the lead scientist for first human trial substituting refined sugars with pure maple syrup The study found significant improvement in multiple cardiometabolic risk factors.    Quebec, CA, November 18, 2024 – A new study published in the The Journal of Nutrition found that substituting two tablespoons of pure maple syrup for refined sugars reduced several cardiometabolic risk factors in humans.  It was the first placebo-controlled clinical trial exploring potential health benefits of maple syrup in humans “We know from decades of research that maple syrup is more than just sugar. It contains over 100 natural compounds, including polyphenols, that are known to prevent disease in part through their anti-inflammatory effects,” remarked Dr. André Marette, PhD  “Because the fundamental chemistry of maple syrup is unique I wondered if ingesting maple syrup instead of an equivalent amount of refined sugar would differently impact the cardiometabolic health and the intestinal microbiota in humans.  The results were extremely encouraging I did not expect to see so many improvements of risk factors within a relatively short treatment period.”    The study was conducted by a Laval University team led by Dr at the Quebec Heart and Lung Institute and Dr at the Institute of Nutrition and Functional Foods Forty-two volunteers from the greater Québec city area Participants substituted 5% of their daily caloric intake (corresponding to 2 tablespoons) from refined sugars with either Canadian maple syrup or an artificially flavored sucrose syrup Each phase lasted 8 weeks with participants switching between maple syrup and sucrose syrup groups after a four-week washout period. The cross-over design ensured that the same test subject was his or her own control Primary outcomes focused on the oral glucose tolerance test the OGTT.  Secondary outcomes included changes in blood lipid profile body fat composition (measured by DEXA scan) and changes in gut microbiota composition Improves Multiple Cardiometabolic Risk Factors Study participants who consumed pure maple syrup had an improved response to the oral glucose tolerance test (OGTT) than those who received a flavored syrup of refined sugar. Their bodies managed blood sugar levels better after eating (-50.59 vs Blood pressure was also lowered in the subjects who consumed maple syrup during the trial  Systolic blood pressure decreased significantly in the maple syrup group (-2.72 mm Hg) while it increased slightly in the sucrose group (+0.87 mm Hg) “Lowering blood pressure continues to be an important factor in lessening the risk of cardiovascular disease,” Dr can be part of an overall solution in helping to prevent metabolic diseases.” Visceral fat is the deep fat that wraps around the internal organs in your belly.  It can increase an individual’s risk of serious health problems such as heart disease The maple syrup trial showed that android fat mass significantly decreased in the maple syrup group as compared to an increase in the group consuming the sucrose solution (-7.83 g vs An unexpected discovery was the improved levels of potentially beneficial gut bacteria and a decrease in levels of potentially harmful gut bacteria in the maple syrup participants The study showed a reduction in Klebsiella species and Bacteroides pectinophilus which are linked to inflammation and metabolic disorders and the increased growth of beneficial bacteria like Lactocaseibacillus casei and Clostridium beijerinckii the study findings are quite significant,” Dr Marette noted.  “The combined decrease of such key risk factors may help to reduce the risk of diabetes and cardiovascular disease Making a commitment to lifestyle changes and small adjustments to our everyday diets is important and can be a powerful tool in preventing future diseases.” According to one participant: “Before the study I would consume pure maple products regularly but not consistently Today my routine is to replace refined sugars with 2 tablespoons of pure Canadian maple syrup daily.” First Human Trial Builds Upon American Researcher’s Cellular and Animal Studies Dr. Marette’s clinical study builds upon his own work in animal models of diabetes and previous work on maple syrup and its bioactives by  American scientist Navindra P. Seeram, PhD Seeram’s extensive foundational work with maple syrup set the stage for this first human clinical trial we learn more benefits that natural products from medicinal plants and functional foods “The significant promising results of this first human trial provide more reasons for us to educate consumers about maple syrup’s many health benefits It is truly a ‘smarter sweetener’ and a healthier alternative to refined sugar.” “While this study was limited to a relatively small sample size (42 men and women) and took place during a relatively short duration of time the results are still significant,” Dr  “We now have human evidence to support replacing refined sugars with maple syrup for preventing metabolic diseases.  Our next goal is to conduct larger studies with other populations to explore how replacing refined sugars with maple syrup might impact their unique health conditions.”      General nutrition claims for 2 tablespoons of maple syrup: The study was jointly funded by Québec Maple Syrup Producers and the Québec Department of Agriculture Fisheries and Food (MAPAQ) through its healthy food production initiative To find out more about  this and other clinical studies about maple syrup, please visit ppaq.ca/en/medias/clinical-study. The Québec Maple Syrup Producers (QMSP) represent over 13,500 maple producers and 8,400 maple enterprises Québec produces 72% of the world’s maple syrup and exports it to over 70 countries.  #       #       # 10.1016/j.tjnut.2024.08.014 Substituting Refined Sugars With Maple Syrup Decreases Key Cardiometabolic Risk Factors in Individuals With Mild Metabolic Alterations: A Randomized The study was jointly funded by Quebec Maple Syrup Producers and the Quebec Department of Agriculture Fisheries and Food (MAPAQ) through its healthy food production initiative are not responsible for the accuracy of news releases posted to EurekAlert by contributing institutions or for the use of any information through the EurekAlert system Copyright © 2025 by the American Association for the Advancement of Science (AAAS) Thanks for visiting four Bundeschampionate qualifiers took place in Germany the winners were 5-year olds Gut Wettlkam's Evée and Elodie and the the 6-year old Djamalla and Special Gold PCH Eleven horses competed in the L-level test for 5-year olds Johanna Wadenspanner topped the board with Gut Wettlkam's DSP mare Evée (by Escolar x San Amour) on a score of 8.2 and 8.5 for submission and general impression Eilika Böye and Evolution Dree Böken (by Escolar x Lauries Crusador xx) followed in second place with 8.0 The Rhinelander gelding is owned by the Werndl family and got 8 for walk 7 for submission and 8 for general impression The M-level dressage horse test for 6-year olds featured 8 pairs and Franz Trischberger and Therese Mercker's Oldenburg mare Djamalla (by Don Romanov x Sir Donnerhall) bested the field with 8.2 Ina-Marie Blass and her own Hanoverian stallion Farrokh (by Finest x Hotline) were second on 8.0 after the black got 8.5 for walk 7.5 for submission and 8.5 for general impression At the qualifier in Vöhl the L-level dressage horse test for 5-year olds had eight combinations at the starters line and Dorothee Lehan rewarded the high score of the class to Katharina Hemmer aboard Gut Neuenhof's Westfalian mare Elodie (by Escolar x Soliman de Hus) They won the class with 8.3 and edged out Claudia Rassmann on Johannes Schmidt's Oldenburg mare Habibi (by For Romance x Dimaggio) with 8.2 The 6-year old class was judged by Ute Kombächer Dieter Scheermann and Elke Hüther and they rewarded Katharina Hemmer a whopping 9.0 for the victory aboard Nancy Gooding's Oldenburg stallion Special Gold PCH (by San Amour x Don Schufro) Philipp Hess and Norma Klemstein's Hanoverian stallion followed in their wake in second place with 8.3 Thanks for visiting The tragic and instant collapse of the Francis Scott Key Bridge in Baltimore in the early hours of Tuesday after a cargo ship apparently lost power and consequently lost steering causing it to ram into one of the bridge supports is an example of how most catastrophes occur: a series of smaller events align to create the disaster that causes harm.  My background as a sailor, along with my experience working in the Electric Boat division of General Dynamics helps me understand some of the details surrounding the accident My position at Boston University’s Questrom School of Business as an operations professor who studies human error and accidents also gives me some unique insight The organizations involved reflect the nature of today’s global supply chains which is owned and operated by Singapore’s Synergy Marine Group to ship its customers’ goods to Sri Lanka via a monthlong voyage There were two local “harbor pilots” on board who are experts in the specific harbor and who are responsible for safely navigating ships in and out of the busy Baltimore harbor Cause: The ship seemed to have an electrical problem (as evidenced by the loss of lights two times before the collision The loss of power meant that the pilots were drifting Smoke was seen rising from the boat as it struck the bridge support suggesting they were logically trying to reverse the boat The current and wind conditions blew the boat into one of the Francis Scott Key Bridge’s support structures at 1:26 am The boat was going about 8 knots due to the current Response: The ship’s crew called Maryland’s Department of Transportation and issued a mayday call to the US Coast Guard moments before the crash which enabled the Department of Transportation to stop traffic going onto the bridge Maryland’s governor called those who stopped additional traffic from entering the bridge after the mayday call “heroes.” Impact on supply chains: The bridge collapse will have a negative impact on the timeliness of delivery of several important goods Ten commercial ships that were headed into Maryland’s port have been forced to anchor outside the harbor Up to 40 shipping vessels are en route to the Port of Maryland and will also likely be affected The Port of Maryland is the 11th busiest port in the US and handles imports of cars the Port of Maryland handled 750,000 vehicles the highest of all US ports in terms of vehicles Maersk’s stock was down 2 percent after the announcement of the accident Prevention: The bridge was built in 1970 and is a “truss” type of bridge with no redundancy to compensate for the loss of a support structure It’s important to note that cargo ships are now two times larger than cargo ships in the 1970s increasing the probability and risk posed by them striking a bridge due to the vessels’ large mass and size the Port of Maryland does not require exiting and entering cargo ships to be escorted by tugboats which could have towed the Dali to safety when it lost its steering ability it seems clear that having tug escorts or availability of tugs seems prudent or adding additional support for vulnerable bridges I suspect the cost of taking these measures seemed prohibitive given the low probability of a ship striking the bridge it is unclear whether there were systematic problems It has been inspected 27 times since it was built in 2015 an inspection in Chile listed a deficiency related to the propulsion and auxiliary machinery—gauges the deficiency was corrected the same day and the last inspection We should ask whether similar problems could happen at other ports Synergy Marine Group’s Founder and Executive Chairman Captain Rajesh Unni warned that current port infrastructure is misaligned with today’s shipping vessels this tragedy is typical of how most accidents occur Rather than being caused by a single mistake or human error a series of minor issues align catastrophically to cause human harm The ship lost power (issue 1) as it was leaving the port before it passed under the bridge (issue 2) strong winds and currents (issue 3) blew it into the bridge which was an old bridge (issue 4) with insufficient support to withstand losing one of its pillars (issue 5) and the Port of Maryland did not require tug assistance so there was no back up for the boat itself when it lost steering (issue 6) All those elements had to be present for the ship to strike the bridge if the ship had lost steerage after clearing the bridge or if the currents were not as strong as they were or if tugboats had been required to help guide the ship it’s probable this would have been just a “near-miss” incident The challenge for organizations and governments is to respond to near-miss incidents by taking measures to prevent future accidents that might have worse outcomes Anita Carson is Larz Anderson Professor in Operations & Technology Management and department chair of operations and technology management at BU’s Questrom School of Business “POV” is an opinion page that provides timely commentaries from students, faculty, and staff on a variety of issues: on-campus, local, state, national, or international. Anyone interested in submitting a piece, which should be about 700 words long, should contact John O’Rourke at orourkej@bu.edu BU Today reserves the right to reject or edit submissions The views expressed are solely those of the author and are not intended to represent the views of Boston University POV: Was the Francis Scott Key Bridge Disaster Avoidable Should the cargo ship have been traveling more slowly Reversing port (left) stern will turn bow to the right toward the bridge support as the inertia from the weight of the boat continues forward into the pylon Reversing starboard (right) i believe would have opposite effect Beyond all this i believe they have bow thrusters to prevent such issues Furthermore i am sure they have alarms going off when they are off their shipping route especially approaching bridges when caprains and his bridge crew should all be paying attention As far as wind and currents being too strong this boat would be clearly in a different position more parallel to the bridge than it was currently in after the impact Power going off at the most critical time is like someone winning the mega lotto It would be very valuable to get some experienced captains in commercial freight their comments rather than opinions from talking heads on news channels Agree completely with this very important post Consider that the Dali was in the channel and properly aligned before the electrical occurrence The Dali was diverted from her vector of trajectory The likeliest cause was human activity such as dropping anchor and effectuating some mechanical steering Engineering must provide for a large margin of shocking human error which is sometimes enhanced by distraction Tug Boats should be required – in the future unfortunately – from point of docking (which they are in this port) past the Bridge to harbor entrance This clearly laid out all of the issues surrounding this tragedy in an interesting and succinct fashion Now let us pray for the six souls lost yesterday morning This disaster will influence managers’ future decisions when dealing with risks of great consequences I would agree wind and current had little or nothing to do with the incident It will be easy enough to tell whether reversing that ship’s engine at high revs would cause the boat to turn the way it appears to turn in the video It’s quite possible the ship has a single screw that rotates clockwise in forward Kicking to port in reverse would be the expected result A tug standing by near the bridge abutment could have pushed the hull in a way that would have steered it away from the bridge without actually being attached to the Dali I’m guessing the statistical possibility of a ship losing steerage entering or leaving a commercial port is negligible They don’t prepare for it because thousands of transits in and out of commercial harbors around the world have never produced this same result It appears at least one of them helped alert law enforcement and saved lives Two pilots onboard means you have at least three people on the bridge potentially acting as captain I have no other facts to support this opinion but I could imagine in a moment of panic three people not used to working as team members could end up working at cross purposes Certainly they would have been usinh all means available to avoid collision Thrusters are less then effective abive three knots I cant imagine she bleed off any more the three knots before the collision There is no mention in the article of the lack of passive protection of the bridge pillars Around the time of the construction of the Baltimore bridge a much smaller vessel hit and demolished the Sunset Skyway Bridge over Tampa bay As a result legislation was written that physical barriers to prevent contact between vessels and bridge supports should be included in all new bridge design but there was no requirement to fit protection retrospectively Four small protective dolphins were installed but they would only stop a rowing boat some by seemingly qualified civil engineers that claim that the presence of many dolphin protections on each side of the bridge would NOT have stopped a ship as big as the Dali While not a professional civil engineer today I did study civil engineering in college performed did many computerized structural analyses of various structures There is zero doubt in my mind that a system of dolphins on both sides of the bridge would have prevented the collapse if not also major structural damage It’s simply a matter of how many and how large they would need to be the Dali was stopped by the pier structure holding up the main support so a dolphin of that size would clearly have worked but far less than the cost of rebuilding that bridge and paying the wrongful death settlements that will arise from this tragedy Enough already with the “dolphins would not have prevented this” talk Let’s identify all similarly vulnerable bridges and start protecting them Pioneering Research from Boston University Castelblanco, 42, of Huntington Beach, was diagnosed with leukemia in 2010 and received a bone-marrow transplant from Vohl, 41, of Stuttgart, Germany, months after her diagnosis. Three years later, the women who didn’t know one another learned they now share a blood type — and some DNA. “Before, I was A-positive, and now I’m B-positive,” Castelblanco said about her changing blood type, as Vohl simultaneously finished the sentence. “And my [bone marrow] DNA is hers. So in the inside, we’re the same.” Tears were shed as Castelblanco, along with her family and friends, gathered at Lake Park in downtown Huntington Beach on Saturday to visit with the woman who saved her life. Delete Blood Cancer DKMS, a New York-based nonprofit that registers donors from around the world and transports bone marrow for transplants, helped organize the afternoon get-together and flew Vohl and her son out to California for a week. “This is a celebration, not only to introduce Yvonne to everyone, but also to thank everybody here for everything that they’ve done,” Castelblanco said. Vohl said she wouldn’t have organized such a large event to announce her arrival, but was humbled by the thanks she received from Castelblanco’s family and friends. “They told me that I’m a hero and that they wanted to bow down [to me],” Vohl said. Monica Pavalko and Shelley Phillipps, friends of Castelblanco, said they’ve been by her side since Day One, helping her with chores and taking care of her family. The two said her strong will and determination is what has kept her going for the past three years. “She never complained or asked, ‘Why me? This sucks,’” Phillipps said. “You felt like you couldn’t cry in front of her. She always said, ‘I’m going to beat this. I’m good.’” On April 22, 2010, Castelblanco was diagnosed with acute myeloid leukemia, a form of cancer that lowered her blood cells and substantially lowered her immunity, said Dr. Vinod Pullarkat, her physician at USC Norris Cancer Hospital. A month before her diagnosis, Castelblanco was participating in a half-marathon in Florida. She said she wasn’t doing well in the run and thought she was tired or hadn’t trained enough. “We got home, and I just kept making excuses for why I wasn’t feeling well,” Castelblanco said. “I was saying I had the flu, or maybe I was pregnant, and all these things as to why I wasn’t doing well.” She was admitted to Hoag Hospital in Newport Beach and underwent a round of chemotherapy, but the leukemia cells were not responding to the treatment, Pullarkat said. Upon further inspection, Castelblanco was discovered to have an aggressive form of leukemia, and the only viable treatment would be a bone-marrow transplant. With advancements in medicine and technology, 70% of patients with acute myeloid leukemia have a chance at surviving, Pullarkat said. In Castelblanco’s case, however, there was a slim success rate. Castelblanco was transferred to City of Hope National Medical Center in Duarte, where Pullarkat was working at the time. The search for a bone marrow donor began immediately with Pullarkat trying to find matching tissue types. Family members were tested, but no one was a match. So Pullarkat turned to the world registry to see if anyone could be a near-perfect donor for his patient. Vohl was 25 years old when she registered herself as a bone marrow donor, she said. The company she was working for put together a registry drive with DKMS, offering time off work and lunch to the employees who joined. Years passed, and Vohl didn’t receive a phone call from the company. Then, in August 2010, she was contacted and told she was a match for someone in the United States. She said she didn’t think twice about donating her bone marrow. “My company gave me holidays,” Vohl said. “DKMS booked the hotel and plane and organized everything.” The Stuttgart resident was flown to Dresden, where doctors checked her physical condition. Once she was cleared, she was given injections to increase her blood count for about five days and was hooked to a machine that would collect stem cells from her blood through an IV rather than from her hip, Vohl said. “It was just two needles [in my arms] and a big machine behind me,” she said. “It wasn’t painful. It was like donating blood. It takes a little bit longer, but it was so easy.” The traditional way to harvest bone marrow was to sedate the donor and collect the cells from the hip, Pullarkat said. But for the past 20 years, doctors have been extracting stem cells through the donor’s blood. “It made the donations much easier,” Pullarkat said. “Bone marrow harvesting is still done, but the majority of the transplants nowadays are done by using blood stem cells. The end result is the same: They both go in the bone marrow, and they will produce new blood.” Those stem cells were then injected into Castelblanco so that her body could begin producing new blood, Pullarkat said. And since the cells are from Vohl, Castelblanco’s blood type changed and her bone marrow DNA matches her donor’s. Castelblanco received the bone-marrow transplant on Sept. 2, 2010, but she still wasn’t in the clear. “You get very sick for a while,” she said. “The first 100 days, post-transplant is a very critical time. Once you get through that magical 100 days, then every month that you stay healthy, your chances [of surviving] become better.” She didn’t stay in the hospital long after her transplant. Castelblanco said she was released 28 days after the procedure, which is better than most patients, but she still had to deal with the side effects of her transplant and medication. Castelblanco developed a cataract in her right eye and experienced some intestinal issues and discoloration of her skin because of graft-versus-host disease (GVHD). “It’s just the new system attacking my body and trying to work on finding its new home,” Castelblanco said. “A lot of my medication is to prevent attacks on my organs and things like that.” Pullarkat said Castelblanco’s case of GVHD isn’t life-threatening and is managed through medication. Because her leukemia is in remission, he considers the transplant a success. Because of privacy and other issues, Castelblanco and Vohl had to wait for two years after the transplant to get each other’s contact information. “It’s to protect the patient and the donor,” Castelblanco said. “I could have had the transplant and still not have done well and maybe not lived. How could you not have a relationship with the person that saved your life? But if you don’t do well, it could have a [negative] reflection on them.” Castelblanco’s dream during those two years was to get ahold of Vohl as soon as she could to thank her. But as soon as she got her contact information in September 2012, Castelblanco didn’t know what to say. “‘Thank you’ just doesn’t sound like enough,” she said. “It so hard to type that emotion in an email, but I think we understood each other.” Castelblanco said she is still under supervision and continuing to recover. She had cataract surgery Aug. 12, and the color in her skin is slowly returning to normal. Vohl said she’s getting a tour around Southern California and will be visiting Disneyland and Hollywood. And once she becomes healthier, Castelblanco said she’s planning to go to Germany to visit Vohl in her home country. “Life just goes on,” Castelblanco said. “You just look at the positives every day, and if something were to reoccur, you just deal with it.” News Subscribe for unlimited accessSite Map This website is using a security service to protect itself from online attacks. The action you just performed triggered the security solution. There are several actions that could trigger this block including submitting a certain word or phrase, a SQL command or malformed data. You can email the site owner to let them know you were blocked. Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page. Volume 9 - 2022 | https://doi.org/10.3389/fnut.2022.740898 This article is part of the Research TopicMobile Health and NutritionView all 4 articles Machine learning (ML) algorithms may help better understand the complex interactions among factors that influence dietary choices and behaviors The aim of this study was to explore whether ML algorithms are more accurate than traditional statistical models in predicting vegetable and fruit (VF) consumption A large array of features (2,452 features from 525 variables) encompassing individual and environmental information related to dietary habits and food choices in a sample of 1,147 French-speaking adult men and women was used for the purpose of this study was measured by averaging data from three web-based 24 h recalls and used as the outcome to predict Nine classification ML algorithms were compared to two traditional statistical predictive models logistic regression and penalized regression (Lasso) The performance of the predictive ML algorithms was tested after the implementation of adjustments as well as in a series of sensitivity analyses such as using VF consumption obtained from a web-based food frequency questionnaire (wFFQ) and applying a feature selection algorithm in an attempt to reduce overfitting Logistic regression and Lasso predicted adequate VF consumption with an accuracy of 0.64 (95% confidence interval [CI]: 0.58–0.70) and 0.64 (95%CI: 0.60–0.68) respectively the most accurate algorithms to predict adequate VF consumption were the support vector machine (SVM) with either a radial basis kernel or a sigmoid kernel both with an accuracy of 0.65 (95%CI: 0.59–0.71) The least accurate ML algorithm was the SVM with a linear kernel with an accuracy of 0.55 (95%CI: 0.49–0.61) Using dietary intake data from the wFFQ and applying a feature selection algorithm had little to no impact on the performance of the algorithms ML algorithms and traditional statistical models predicted adequate VF consumption with similar accuracies among adults These results suggest that additional research is needed to explore further the true potential of ML in predicting dietary behaviours that are determined by complex interactions among several individual despite several public health efforts and policies adhering to healthy eating remains a challenge the present study is one of the first to compare ML algorithms to traditional statistical models to predict a dietary behavior the aim of this study was to explore and compare the performance metrics of ML algorithms and traditional statistical models to predict a simple healthy dietary behavior adequate vegetable and fruit (VF) consumption We hypothesized that ML algorithms are more accurate than traditional statistical models in predicting adequate VF consumption We stress that this analysis was not intended to provide a definitive predictive model of adequate VF consumption Once all questionnaires had been completed participants were invited to their regional's research center for clinical assessment (anthropometric measurements and blood sampling) The project was conducted in accordance with the Declaration of Helsinki and was approved by the Research Ethics Committees of Université Laval (ethics number: 2014-271) Centre hospitalier universitaire de Sherbrooke (ethics number: MP-31-2015-997) Montreal Clinical Research Institute (ethics number: 2015-02) and Université du Québec à Trois-Rivières (ethics number: 15-2009-07.13) The set of predictor variables and their corresponding features were derived from all questions and scores from all questionnaires listed in Supplementary Table 1 A variable represented a question in a given questionnaire while its corresponding features reflected the transformed variable dummy variables for each response to that question fasting blood glucose and insulin concentrations systolic and diastolic blood pressures were also considered as features in each model and algorithm body fat percentage and waist circumference were considered as features in all models and algorithms Questions that had been completed by <70% of the participants were excluded Missing data for continuous features were imputed using the study population averages for each feature The categorical variables were dummy coded with a specific binary code for missing data Once categorical variables were dummy coded total number of predictor features included on all models and algorithms was 2,452 The outcome predicted (classes) was VF intake dichotomized as adequate/inadequate, based on the population target in Québec of 5 or more servings/d (27) the two classes were 1- adequate VF consumption corresponding to 5 or more servings/d and 2- inadequate VF consumption the list of discriminant features retained in the LR SVM linear and Adaboost models and algorithms were compared to verify any similarities or differences The discriminant analysis was conducted by identifying the 10 features with the highest coefficients for LR Gini feature importance was used for the discriminant analysis of the RF and Adaboost algorithms and Entropy importance was used for the DT algorithm All features retained by the SCM corresponded to the discriminant features for this algorithm KNN does not rank features based on importance and SVM (polynomial radial basis and sigmoid) are uninterpretable data from these algorithms were not included in the discriminant analysis Predictive metrics and corresponding equations Table 3 shows characteristics of the 1,147 participants (572 women The majority of participants had a university degree and were Caucasian The mean (±standard deviation) VF consumption evaluated by the R24W in the sample was 5.5 ± 3.1 servings/d (interquartile range = 4.0) with 52.3% of participants consuming 5 or more servings/d The mean VF consumption evaluated by the wFFQ was 7.6 ± 5.0 (interquartile range = 4.8) with 67.6% consuming 5 or more servings/d Sociodemographic characteristics of the French-speaking adults from Quebec Table 4 presents the metrics of all models and algorithms predicting adequate VF consumption (≥5 servings/d) based on normalized data among all participants There are no significant differences in accuracy between models and algorithms and no important differences for other performance metrics When predicting inadequate VF consumption (<5 servings/d) instead of adequate VF consumption there were no differences in performance between traditional statistical models and ML algorithms (not shown) Performance metrics of two traditional statistical models and nine machine learning algorithms to predict adequate vegetable and fruit (VF) consumption based on dietary intake data obtained from web-based 24-hr recalls (R24W) among1147 French-speaking adults from Québec Figure 1 presents the top discriminant features included in seven of the classification models and algorithms. Discriminant features are colour-coded for illustrative purposes to allow rapid visual comparison. Figure 1 shows that the discriminant features predicting adequate VF consumption are inconsistent across models and algorithms While the traditional classification models LR and Lasso shared eight top discriminant features there is little coherence between the discriminant features of the five ML algorithms No single feature was included as a top discriminant feature in all seven models and algorithms Discriminant features retained in the logistic regression (LR) and Lasso models and in the decision tree (DT) support vector machine (SVM) with a linear kernel and Adaboost machine learning algorithms to predict adequate vegetable and fruit consumption Features are colour-coded according to the questionnaire to which they belong; different shades within a given color indicate that more than one feature of a questionnaire was retained; numbers indicate the rank of a given question from a given questionnaire retained in the model or algorithm Social support for healthy eating questionnaire; BIDR Balanced inventory of desirable responding; FLQ Sensitivity to punishment and sensitivity to reward questionnaire sensitivity and F1 scores were also higher when using intake data from the wFFQ compared to data from the R24W AUROC values for all models and algorithms were lower when using data from the wFFQ compared to data from the R24W except for the Lasso model for which the AUROC value slightly increased Performance metrics of two traditional models and nine machine learning algorithms to predict adequate vegetable and fruit (VF) consumption based on dietary intake data obtained from a web-based food frequency questionnaire (wFFQ) among1147 French-speaking adults from Québec The accuracy of traditional statistical models and of ML classification algorithms increased when dietary features known to be correlated with VF consumption were included in the analyses (Figure 2). Other performance metrics are reported in Supplementary Table 4 Accuracy of the various ML classification algorithms in predicting adequate VF consumption was once again not superior to accuracy seen with traditional statistical models Comparing the accuracy of traditional statistical models and machine learning algorithms to predict adequate vegetable and fruit (VF) consumption when other dietary intake features are included in addition to the 2452 features originally included as well as components of the Canadian Healthy Eating Index (C-HEI) other than the VF component and the C-HEI score itself Finally, reducing the number of features to 5, 10, and 50 features with a feature selection algorithm attenuated overfitting for most models and algorithms, but had trivial and inconsistent impacts on accuracy values and other metrics (Supplementary Figure 2; Supplementary Table 5) the accuracy of all models and algorithms remained low and no differences were observed between traditional statistical models and ML algorithms when fewer features were used to predict an adequate VF consumption The successful use of ML in several healthcare fields suggests promising applications in the field of nutrition epidemiology and public health nutrition. However, the superiority and advantages of ML-based classification approaches compared with more traditional statistical approaches need to be evaluated, validated, and confirmed in all fields of application (3, 12, 37) The objective of this study was to compare the performance metrics of ML algorithms to those of more traditional statistical models in predicting a tangible and simple dietary behavior The hypothesis that ML classification algorithms outperform traditional statistical classification models when predicting adequate VF consumption based on a wide spectrum of individual social and environmental data was not supported by our experimental data accuracy of all models and algorithms increased when dietary intake data from the wFFQ were used in place of data from 24-h recalls VF consumption measured over longer periods of time and may therefore be more stable than when measured using average data from three 24-h recalls this did not materialize into better performance metrics of ML classification algorithms compared to traditional statistical models The fact that food frequency questionnaires are more prone to systematic error than 24-h recalls apparently did not negatively influence performance metrics of traditional statistical models and of ML classification algorithms tended to slightly or substantially overfit despite normalizing the data from continuous features and adjusting hyperparameters to minimize overfitting and to optimize performances Applying a feature selection algorithm to reduce the number of features included in the analyses lowered overfitting for all models and algorithms accuracy improved for the majority of the models and algorithms when dietary features closely associated with VF intake were included but overall performance of ML classification algorithms and traditional statistical models remained comparable The compelling observation is that the ML classification algorithms tested in the present study do not predict adequate VF consumption with more accuracy than traditional statistical models when using a large set of features Since the primary aim of this exploratory analysis was to compare predictive accuracy of different models and algorithms multicollinearity did not have to be addressed Future studies designed to identify discriminant features of adequate VF consumption or any other dietary behavior with traditional statistical models or with ML algorithms will need to consider multicollinearity Our study also has the following strengths this is the first study to compare ML algorithms with traditional statistical models to predict a dietary behaviour We also used nine wellknown ML classification algorithms to conduct analyses Algorithms showing strong predictive performances will have limited application if execution time is long all algorithms used in this study had relatively short execution time we included a rather large number of features which could have allowed ML algorithms to capture non-linear and complex interactions the number of features used may still be considered small according to some standards in the ML field The extent to which ML classification algorithms outperform traditional statistical models when much larger and complex datasets are used to predict a dietary behavior outcome remains to be investigated ML presents important opportunities for advancing the field of nutritional epidemiology and public health nutrition our results suggest caution regarding the use and added-value of ML classification algorithms to predict diet-related variables and outcomes in the context of predicting adequate VF consumption ML classification algorithms did not perform better than traditional statistical models Further research is needed to identify contexts for which ML algorithms are best suited The raw data supporting the conclusions of this article will be made available by the authors The studies involving human participants were reviewed and approved by Université Laval (Ethics Number: 2014-271) Centre hospitalier universitaire de Sherbrooke (Ethics Number: MP-31-2015-997) Montreal Clinical Research Institute (Ethics Number: 2015-02) and Université du Québec à Trois-Rivières (Ethics Number: 15-2009-07.13) The patients/participants provided their written informed consent to participate in this study ÉC and DB contributed to some of the statistical modeling as well as to generating the data used in this study and BL obtained funding for the PREDISE study FL has contributed to the conceptualization of the analyses and the modeling BL is the author responsible for this work All authors contributed to the article and approved the submitted version MC received a scholarship from the Fonds de recherche du Québec-Santé The funding organisations were not involved in the writing of this article The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher MCV is Tier 1 Canada Research Chair in Genomics Applied to Nutrition and Metabolic Health The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnut.2022.740898/full#supplementary-material web-based food frequency questionnaire; KNN Artificial intelligence in medicine: what is it doing for us today CrossRef Full Text | Google Scholar Artificial intelligence in health care: a report from the national academy of medicine Time to reality check the promises of machine learning-powered precision medicine (2020) 20:2345 doi: 10.1016/S2589-7500(20)30200-4 machine learning algorithms outperform conventional regression models in 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Benoît Lamarche, YmVub2l0LmxhbWFyY2hlQGZzYWEudWxhdmFsLmNh Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish either observed and verified firsthand by the reporter or reported and verified from knowledgeable sources Translations may contain inaccuracies—please refer to the original content "We know from decades of research that maple syrup is more than just sugar," Dr that are known to prevent disease in part through their anti-inflammatory effects." Metabolic disease is an umbrella term given to obesity and related diseases A high-sugar diet and inflammation are two known risk factors for metabolic disease and there has long been a debate among nutrition experts and scientists as to whether all forms of sugar are equally harmful to health "Because the fundamental chemistry of maple syrup is unique I wondered if ingesting maple syrup instead of an equivalent amount of refined sugar would differently impact the cardiometabolic health and intestinal microbiota in humans," said Marette I did not expect to see so many improvements of risk factors within a relatively short treatment period." and for eight weeks one group substituted 5 percent of their daily caloric intake of food with Canadian maple syrup and the other group swapped the same amount of calories for artificially flavored sucrose syrup there was a four-week washout period when the participants went back to their usual diets before they spent another eight weeks eating the other sugar This meant that the participants all experienced eight weeks eating each form of sugar so the scientists could directly compare the effects of eating the equivalent of two tablespoons of Canadian maple syrup with two tablespoons of sucrose syrup The scientists concluded that eating maple syrup rather than artificial syrup improved several markers of metabolic disease their bodies afterwards responded better to the sugars in their blood compared to when they ate the artificial syrup Individuals in the maple syrup group showed significant improvements in blood pressure while those in the sucrose group had higher blood pressure than on their regular diets Abdominal fat is linked to an increased risk of heart disease stroke and other metabolic conditions—but the scientists found that participants swapping their sugars for maple syrup lost abdominal fat and those eating sucrose gained abdominal fat the study findings are quite significant," said Marette "The combined decrease of such key risk factors may help to reduce the risk of diabetes and cardiovascular disease." "We now have human evidence to support replacing refined sugars with maple syrup for preventing metabolic diseases," said Marette "Our next goal is to conduct larger studies with other populations to explore how replacing refined sugars with maple syrup might impact their unique health conditions." One of the study participants said in a statement: "Before the study I would consume pure maple products regularly Today my routine is to replace refined sugars with two tablespoons of pure Canadian maple syrup daily." This study was published in The Journal of Nutrition. It was conducted by a team of scientists at Laval University led by Marette at the Quebec Heart and Lung Institute Marie-Claude Vohl at the Institute of Nutrition and Functional Foods The research was partly funded by Quebec Maple Syrup Producers which represents 13,500 producers of maple syrup and 8,400 maple enterprises Do you have a tip on a food story that Newsweek should be covering? 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Let us know via science@newsweek.com and your story could be featured in Newsweek Newsweek is committed to challenging conventional wisdom and finding connections in the search for common ground Newsletters in your inbox See all Sheila Long is making a huge impact on students as a longtime school crossing guard — A Weirton woman says it was her dream to be a teacher And while you won’t find Sheila Long in a classroom she's still making a huge impact on students as a longtime school crossing guard you'll find her at the intersection of Euclid Avenue and Brightway along Marland Heights in Weirton “People say I know their cars more than I know their faces,” she said they say ‘I know who you are,’ and I say ‘what kind of car do you drive?’’’ Long sees to it that students make it safely off the bus and across the street “Many times I've had to jump out of the way ‘listen to the rules because I don't want anything to ever happen to you.’’’ “I've had two (kids) graduate already one is ready to graduate this year and one's a 4th grader She's been wonderful,” parent Sharon Krutilla says of Long Long gets a second helping of students at lunch time as a cook in the cafeteria at Weir Middle School Whenever I go up sometimes she comes around and gives me a hug to feel like I'm home or here getting off the bus and it's just a really special feeling to me,” student Kylie Dean said That special attention is appreciated by parents like Carlo Volhl who waits for his 9-year-old son to get off the bus each day which is thing we've been working for on while,” Vohl said “A real feeling of community here with everybody and it's nice to have someone like that on your side.” And these kids know Long pulls out all the stops She often takes the students for ice cream “She has donuts in the morning and drinks for them Long finds another special way to celebrate the kids hard work with water and everyone brings water balloons and guns and we all have a water fight,” student Darren Thompson said This week’s Shining Star is a charismatic crossing guard finding ways to spread love with a little direction and you just need to show them love and that makes me feel good,” Long said “When I go home at night and lay my head on the pillow and know I did what God wants me to do and these kids know their loved.” Sheila is also a youth ministry leader in Weirton through the Awana organization and carpools kids to the program on a weekly basis but says all the kids in her neighborhood are like her own If you know someone, who goes above and beyond at their job, like Long, let us know. Nominate your Shining Star here You could see them featured right here on NEWS9 NEW YORK (AP) - Disney has found its latest princess: 14-year-old native Hawaiian Auli'i Cravalho (aw-LEE'-ee crah-VOHL'-oh) Cravalho was announced Wednesday as the star of Disney's upcoming animated adventure "Moana." This document may not be reprinted without the express written permission of Chattanooga Times Free Press Material from the Associated Press is Copyright © 2025 audio and/or video material shall not be published rewritten for broadcast or publication or redistributed directly or indirectly in any medium Neither these AP materials nor any portion thereof may be stored in a computer except for personal and noncommercial use The AP will not be held liable for any delays errors or omissions therefrom or in the transmission or delivery of all or any part thereof or for any damages arising from any of the foregoing Together with his criticisms of the Smithsonian representing un-American ideologies Trump signed an Executive Order today demanding that the Nobel Prize committee abandon “woke and DEI” policies and grant prizes to people that really earn them the Committee has granted prizes to undeserving recipients Marie Curie should have never gotten one She should return it and let someone else get the Peace Prize.” He added that Barack HUSSEIN Obama didn’t do anything to deserve his Look what I’ve done for the Ukraine.” Stephen Miller declared that it was the President’s intention that Oslo better shape up soon or we’d conquer Scandinavia Peter Hegseth quoted on Signal. JD Vance was present for the signing and said /satire (the foregoing is fictional and should not be taken for actual quotes) Not signed up for Daily Kos yet? Create a free account Metrics details An Erratum to this article was published on 01 April 2005 Palmar xanthomas are characterized by a brownish, yellowish coloration of the palmar striae and are pathognomonic of type III dyslipidemia. palmar xanthomas and features of type III (presence of β-VLDL VLDL-cholesterol/TG ratio > 0.5) were observed among DM1-apo E2 heterozygotes individuals DM1 individuals carrying the E2 allele (heterozygotes or homozygotes) tend to express palmar xanthomas whereas unaffected apo E2 heterozygotes relatives do not Our observations suggest that the simultaneous presence of DM1 and apo E2 allele promote type III expression as shown by the familial evaluation of palmar xanthomas distribution the search for palmar xanthomas while performing DM1 patients' physical examination might contribute to specify health status and identify the pattern of LD between DMPK and apo E loci Patterns of linkage disequilibrium in the human genome Cloning of the essential myotonic dystrophy region and mapping of the putative defect Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy Genealogical reconstruction of myotonic dystrophy in the Saguenay-Lac-Saint-Jean area (Quebec The pleiotropoic expression of the myotonic dystrophy protein kinase (MDPK) gene illustrates the complex relationships between genetic biological and clinical covariates of male aging Type III hyperlipoproteinemia (dysbetalipoproteinemia): The role of apolipoprotein E in normal and abnormal lipoprotein metabolism Linkage of myotonic dystrophy and apo E in a French-Canadian isolate Myotonic dystrophy: Linkage with apolipoprotein E and estimation of the gene carrier status with genetic markers Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI Download references This project was supported by the ECOGENE-21 project (CIHR/CAHR program grant no. CAR43283). D. Brisson is recipient of a doctoral studentship from the Canadian Institutes for Health Research (CIHR), Fournier Pharma, and the “Réseau en santé cardiovasculaire-FRSQ.” M.C. Vohl is a research scholar from FRSQ. D. Gaudet is the chairholder of the Canada Research Chair in preventive genetics and community genomics (http://www.chairs.gc.ca) Montreal University Community Genomic Medicine Center and Chicoutimi Hospital Lipid Clinic Chicoutimi Hospital Neuromuscular Diseases Clinic Jonquiere Hospital Lipid Research Center and Department of Food Sciences and Nutrition Laval University Download citation DOI: https://doi.org/10.1097/01.GIM.0000157130.81975.FE Metrics details a peroxisome proliferated activated receptor alpha (PPARα) agonist has been shown to decrease plasma triglyceride (TG) and increase plasma high-density lipoprotein (HDL) cholesterol levels despite a large interindividual variation in the response Fenofibrate-activated PPARα binds to a DNA sequence element termed PPAR response element (PPRE) present in regulatory regions of target genes A PPRE has been identified in the proximal 5′ flanking region of the gene encoding the liver fatty acid binding protein (LFABP) LFABP is a small cytosolic protein of 14 kDa present in the liver and the intestine and is a member of the superfamily of the fatty acid binding proteins (FABPs) FABPs play a role in the solubilization of long-chain fatty acids (LCFAs) and their CoA-ester to various intracellular organelles FABPs serves as intracellular acceptors of LCFAs and they may also have an impact in ligand-dependent transactivation of PPARs in trafficking LCFAs to the nucleus Since PPARs are known to regulate the transcription of many genes involved in lipid metabolism the importance of LFABP in fatty acid uptake has to be considered The aim of this study was to verify whether genetic variations in the LFABP gene may impact on plasma lipoprotein/lipid levels in the fasting state as well as on the response to a lipid-lowering therapy with fenofibrate on plasma lipids and obesity variables We also wanted to verify whether the presence of the PPARα L162V mutation interacts with genetic variants in LFABP gene we first determined the genomic structure of the human LFABP gene and then designed intronic primers to sequence the coding regions and the promoter region of the gene in 24 patients showing divergent plasma lipoprotein/lipid response to fenofibrate Sequence analysis revealed the presence of a T94A missense mutation in exon 3 Interspecies comparison revealed that threonine 94 is conserved among species We subsequently screened another sample of 130 French Canadian subjects treated with fenofibrate for the presence of the LFABP T94A mutation Carriers of the A94 allele were at increased risk to exhibit plasma TG levels above 2.00 mmol/l after treatment with fenofibrate [2.75 (1.03–7.34); OR 95% confidence interval (CI)] carriers of the A94 allele were characterized by higher baseline plasma-free fatty acid levels (FFA) (p=0.01) and by a lower body mass index (BMI) (p=0.05) and waist circumference (p=0.005) than T94 homozygotes PPARα L162V and LFABP T94A showed to have a synergistic effect on BMI (p interaction = 0.03) These results suggest that the LFABP T94A missense mutation could influence obesity indices as well as the risk to exhibit residual hypertriglyceridmia following a lipid-lowering therapy with fenofibrate and TG levels were enzymatically measured on a Multiparity Analyser CX7 (Beckman This study received the approval of the Chicoutimi Hospital ethics committee All exons and exon-intron boundaries were amplified from genomic DNA by use of specific primers derived from all 5′ and 3′ end of intronic sequences (Table 1) The annealing temperature for all pairs was 60°C Polymerase chain reaction (PCR) conditions were 50 ng genomic DNA and 0.4 μmol/l primers in a 50-μl reaction PCR products were purified (Multiscreen; Millipore Sequencing reactions were performed using BigDye Terminator v3.0 cycle sequencing (ABI Prism and the products were analyzed on ABI 3700 automated DNA sequencer (PE Applied Biosystems) The gel files were processed using the ABI Prism 3700 data collection software applied biosystem version 1.1 and ABI Prism DNA sequencing analysis software (PE Applied Biosystems) then assembled and analyzed using the STADEN preGap4 and Gap4 programs The LFABP T94A mutation does not alter any restriction site; thus the mismatch PCR method was performed using primers LFABPex3.L-mismatch (5′-CAGTTGGAAGGTGACAATAAACTGGTGAAA-3′ mismatch is underlined) and LFABPex3.R (5′-ATACTGACCACAGGAAAGAAGTTTGGGG-3′) Digestion products were electrophoresed through 4% agarose gel and stained with ethidium bromide followed by digestion with Hha I restriction enzyme and the ApoE genotype were considered in this model odds ratios (OR) with 95% CI of reaching TG and TC/HDL-C ratio target values associated with LFABP T94A genotype were reported following fibrate treatment Analyses of covariance were also conducted to evaluate the mean phenotypic differences at baseline and in response to the treatment therapy between carriers and noncarriers of the LFABP T94A mutation A 2×2 ANOVA was used to evaluate the possible interaction between LFABP T94A and PPARα L162V genotype on plasma lipid variables Statistical analyses were performed using SAS (SAS institute Schematic representation of the human liver fatty acid binding protein (LFABP) gene. Upper panel a representation of the human messenger RNA. The coding region is shaded, and arrows indicate translation start (met) and stop codon (UAA). The spatial localization of exons within the gene and the intron size is shown in the lower panel. The gene spans 5.1 kb of genomic DNA Plasma triglyceride (TG) concentrations before treatment (pre-Tx) and after treatment (post-Tx) with fibrate, among LFABP T94 HMZ and carriers of liver fatty acid binding protein (LFABP) A94 allele. Data are mean ± SE. All values were adjusted for age, gender, BMI, ApoE, alcohol, and smoking Plasma cholesterol concentrations before treatment (pre-Tx) and after treatment (post-Tx) with fibrate among liver fatty acid binding protein (LFABP) T94 HMZ and carriers of the LFABP A94 allele Asterisk is allowed for significant difference No other significant difference between genotypes in reaching the target values were observed To evaluate the interaction between LFABP T94A and PPARα L162V polymorphisms, subjects were divided into four genotype groups based on the presence or absence of the two variants. No difference was observed between the four genotype groups for waist girth, TG, FFA, LDL-C, HDL-C, TC, and fasting glycerol levels as well as for the TC/HDL-C ratio (Table 4) carriers of both mutations tended to have a lower BMI and the gene-gene interaction effect was found to be significant (p=0.03) The human LFABP gene has been mapped on chromosome 2p11 we have determined the exon-intron structure of the human LFABP gene Direct sequencing of the entire coding region of the human LFABP gene as well as exon-intron boundaries revealed the presence of an A to T substitution in exon 3 This substitution leads to a T94A missense mutation Comparison with other species revealed that T94 is well conserved among species like Rattus Norvegicus and Mus Musculus This suggests that the threonine 94 could be important to assure the physiological role of the protein Effect of peroxisome proliferated activated receptor alpha (PPARα) L162V liver fatty acid binding protein (LFABP) T94A and their interaction on BMI (kilograms per meter squared) sequencing of the entire coding region allowed us to identify a T94A missense mutation in the LFABP gene Carriers of the A94 allele were at increased risk to exhibit residual hypertriglyceridemia above the therapeutic target following therapy with fenofibrate The A94 allele is also associated with a lower BMI and waist girth and higher fasting FFA concentrations Mutations LFABP T94A and PPARα L162V interact together to modulate BMI Functional studies as well as longitudinal and prospective studies will be required to elucidate how the LFABP T94A mutation can lead to the observed effects Bass NM (1988) The cellular fatty acid binding proteins: aspects of structure Bergeron J et al (2002) Influences of the PPAR alpha-L162V polymorphism on plasma HDL(2)-cholesterol response of abdominally obese men treated with gemfibrozil Vohl MC (2003) The peroxisome proliferator-activated receptor alpha L162V mutation is associated with reduced adiposity Bass NM (1990) Induction of fatty acid binding protein by peroxisome proliferators in primary hepatocyte cultures and its relationship to the induction of peroxisomal beta-oxidation Perron P et al (2002) Effect of apolipoprotein E peroxisome proliferator-activated receptor alpha and lipoprotein lipase gene mutations on the ability of fenofibrate to improve lipid profiles and reach clinical guideline targets among hypertriglyceridemic patients Oscarsson J (2001) Effects of fatty acids and growth hormone on liver fatty acid binding protein and PPARalpha in rat liver Am J Physiol Endocrinol Metab 281:E772–E781 Grundy SM (1997) National Cholesterol Education Program recommendations for cholesterol testing in young adults McPherson PR (2000) Recommendations for the management and treatment of dyslipidemia Report of the working group on hypercholesterolemia and other dyslipidemias Evans RM (1996) The peroxisome proliferator-activated receptors: ligands and activators Ordovas JM (2001) 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L-cell fibroblasts expressing rat liver fatty acid-binding protein Schroeder F (2000) Microsomal fatty acyl-CoA transacylation and hydrolysis: fatty acyl-CoA species dependent modulation by liver fatty acyl-CoA binding proteins Eacho PI (2000) Ligand-dependent interaction of hepatic fatty acid-binding protein with the nucleus Li L et al (2002) Influence of peroxisome proliferator-activated receptor alpha agonists on the intracellular turnover and secretion of apolipoprotein (Apo) B-100 and ApoB-48 Bader M et al (2003) Decreased liver fatty acid binding capacity and altered liver lipid distribution in mice lacking the liver fatty acid-binding protein gene Schroeder F (1996) Liver fatty acid-binding protein expression in transfected fibroblasts stimulates fatty acid uptake and metabolism Prevention of coronary heart disease in clinical practice (1998) Recommendations of the second joint task force of European and other Societies on coronary prevention Schroeder F (1995) Intestinal and 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acid-binding proteins Download references C. Brouillette is the recipient of a studentship from the “Fonds de la recherche en santé du Québec Fonds pour la formation de chercheurs et l’aide à la recherche (FRSQ-FCAR santé)”. Y. Bossé is the recipient of a doctoral studentship from the Canadian Institutes of Health Research. M.C. Vohl is a research scholar from the FRSQ. D. Gaudet is the chairholder of the Canada research chair in preventive genetics and community genomics (http://www.chairs.gc.ca) This study was supported by ECOGENE-21 (CIHR-CAR #43283) Department of Social and Preventive Medicine Download citation DOI: https://doi.org/10.1007/s10038-004-0171-2 Journal of Assisted Reproduction and Genetics (2016) Kadokawa Haruki Jimusho's official website for Issui Ogawa's Michibiki no Hoshi (Star of Guidance) science fiction novel series revealed on Thursday that an anime project is in the works. A "screen adaptation" project is in the works for completion in fall of 2018 The site describes the novel series' story: and Gibraltar Kōbōsen (The Battle of Gibraltar) in 2005 Thanks to Dennis R for the news tip [Via Yusuani] showcases some of the best action sequences of 2021 and stunts fail to deliver a promising story The flaw has now become a curse for an action genre where someone or the other may randomly tell you “Action films don’t have a story With a little bit of storytelling at its disposal The Protege thematically visits the past of its two titular characters Anna Dutton (Maggie Q) and Moody Dutton (Samuel L While the Dutton’s are the best-paid assassins you may get in Protege’s universe it is the anti-force Michael Rembrandt (Michael Keaton) who steals the show Jackson) is an ace assassin who takes up high-profile contracts from all around the globe Moody visits Vietnam to finish an assignment Moody takes Anna under his wings and travels back to England and informs him that she orchestrated the plan not for money but for Don Preda where Anna runs an elegant bookstore at the street corner Moody had Lucas’ location until 1998 As Anna investigates the mystery of Lucas Hayes Anna’s techno informer Billy and Moody’s caretaker Everything related to Lucas Hayes traces back to Anna’s homeland Anna found out Lucas Hayes was the son of Edward Hayes Edward was a businessman indicted for war crimes who was killed in a car explosion in Da Nang Anna saw Moody standing in the crowd near the crime scene and speculated that Moody would have bombed Edward’s car After his father’s murder on Christmas day Lucas stayed in Paris until 1998 but returned to Da Nang in March 1999 He was admitted to St Quiteria Hospital on June 2nd after which there was no record of his existence Anna visited Edward’s business partner and Co-CEO Vohl’s personal attorney Duquet shot Vohl without a blink and captured Anna at the company’s building Their gang was killing anyone and everyone investigating Lucas Hayes After a bit of an “action” struggle Anna fled from captivity and ended up at Lucas’ last known location The nun at the hospital showed the wrong person only one person could give satisfactory answers to Anna’s curiosity Anna discovered that both Moody and Edward were alive Moody tricked Edward’s hired assassin Moody and Anna infiltrated Edward’s stronghold on a secluded island and planned to kill him during his extravagant charity event Edward was escorted to his “panic bunker” to save his life Moody was waiting for him there with a ticking bomb in his bag Edward confessed that he faked his death to protect his beloved son Moody sarcastically laughed at Edward’s emotional plea and underlined that Edward did all to save himself The fake death was Edward’s chance to disappear as no one looks for a dead man Edward ran his crime syndicate from the secluded island Moody also conveyed his addictive voyage to find Lucas Moody felt remorseful for taking away a father from a son How could he have known that the web of affairs of rich criminals is beyond anyone’s understanding When the confessions were done and dealt with The pursuit of Edward Hayes was Moody’s journey and it didn’t hold enough closure for Anna’s character and facing it would only bring full closure A bleeding Anna left the island and visited the location in Da Nang She sent the location coordinates to Rembrandt to finish the last chapter of the story Anna had shown the disconcert to remember her haunting past she didn’t remember it or didn’t want to remember it and thus she didn’t want to visit Vietnam as the lands would have revived her memory Anna remembered how Vietnamese militants killed her American father the leader captured Anna and took her to their den He assembled two of the one guns in front of Anna and decided to sleep with young Anna Anna had an exceptional talent since childhood and had learned the technique of assembling guns by just observing she pointed a gun at him and killed the three militants inside the den It was the horrific memory Anna had been hiding all along Rembrandt reached the militant’s den and requested Anna to drop the gun and reconcile their relationship But Anna yearned for closure and peaceful life She wouldn’t have been able to live it until Rembrandt’ was alive Anna killed Rembrandt and walked out of the door The Protege is a 2021 Action Thriller film directed by Martin Campbell