on their way into the treehouse to watch the birds fly along the river BACK TO TOPTV Listings Email Newsletters RSS Feeds Contests and Rules Contact Us Careers at WJXT / WCWJ Closed Captioning / Audio Description WJXT Public File WJXT EEO Report WCWJ Public File WCWJ EEO Report Terms of Use Privacy Policy Do Not Sell My Info FCC Applications Copyright © 2025 News4JAX.com is managed by Graham Digital and published by Graham Media Group TV Listings Email Newsletters RSS Feeds Contests and Rules Contact Us / Follow on Social Media Careers at WKMG Closed Captioning / Audio Description Public File Current EEO Report Terms of Use Privacy Policy FCC Applications EEO Report Disability Assistance Copyright © 2025 ClickOrlando.com is managed by Graham Digital and published by Graham Media Group Tropical cyclone formation is not expected during the next 7 days Routine issuance of the Tropical Weather Outlook will resume on May 15 Special Tropical Weather Outlooks will be issued as conditions warrant 2 weeks ago by NHC Forecaster Forecaster Hagen The monsoon trough axis enters the Atlantic near the coast of Guinea-Bissau at 12N16W and extends south-southwestward to 05N21W The ITCZ continues from 05N21W to the coast of Brazil at 01N50W Scattered moderate and isolated strong convection is occurring from 01N-06N between 10W-18W Scattered moderate convection is ongoing from 04N-08N between 25W-45W a stationary front extends from central Florida westward to 27N94W where it becomes a warm front to the S Texas coast Widely scattered moderate convection is occurring within 60 NM of the front Winds north of the stationary front west of 95W are fresh ESE winds are gentle or moderate across the Gulf Seas are 1-2 ft in the E Gulf and 2-4 ft in the W Gulf Florida to S Texas will gradually wash out Gentle to moderate winds dominating the western basin will strengthen tonight through Wed morning Winds will pulse to moderate to fresh in the Straits of Florida through mid- week A weak front may reach the NW Gulf mid- week Smoke from agricultural fires in southeastern Mexico is creating hazy conditions in some sections of the western Gulf with the lowest reported visibility near the SW Gulf coast With a weak pressure gradient between the Bermuda-Azores High north of the Caribbean and a 1009 mb Colombian Low trades are only gentle to moderate across the Caribbean this morning Seas are 1-4 ft across the forecast waters There is widely scattered moderate convection south of 12N between 75W-80W in association with the E end of the Pacific monsoon trough moderate to fresh east to southeast winds will pulse north of Honduras increasing to fresh to strong speeds nightly starting Tue night Winds will pulse to fresh nightly near the Windward Passage Gentle to moderate trades and slight to moderate seas are expected over the remainder of the basin through the period A surface trough extends from 21N59W to 25N63W supported by a collocated upper level trough Winds north of 23N between 50W-62W are E to SE fresh to strong with seas 6-9 ft Scattered moderate convection is occurring from 20N-30N between 50W-60W A stationary front is located from the NE Florida coast north-northeastward to 31N80W with scattered moderate convection north of 29N between 76W-79W winds across the forecast waters are gentle to moderate with seas 4-7 ft in mixed wind waves and N swell the fresh to locally strong northeast winds and moderate to rough seas will gradually shift westward through the early part of the week as the trough drifts westward A stationary front along the southeastern U.S Coast will gradually lift back northwest as warm front through the middle of the week then may slowly push offshore again at the end of the week Expect scattered to numerous showers and thunderstorms over the western waters in the early part of the week Posted 3 hours ago by NHC Forecaster Landsea has amassed an impressive $3 million net worth Her financial success places her among the elite model athletes globally and success in numerous fitness competitions 2024 · carriejune anne bowlby is an american bodybuilder and social media fitness influencer who is rated one of the top ten most successful fitness models in the world 2021 · this is all you need to know about the life and career of carriejune anne bowlby and how she rose to become a highly admired fitness model Join our community dedicated to helping you 2024 · carriejune anne bowlby is an american fitness model and social media celebrity born on 7 february 1996 in new jersey 1996 · instagram model and influencer who is known for posting fitness and lifestyle photos to her misscarriejune account She developed an interest in exercising as a student and participated in track & field and cheerleading 2024 · carriejune anne bowlby is a prominent instagram model and influencer recognized for her engaging content revolving around fitness and lifestyle on her misscarriejune account she has successfully cultivated a dedicated online community Learn the beast of a story behind fitness coach and where her motivation comes from to provide community and motivation for men and women of all ages Loraincounty Us Jury Osu Employee Salaries Beachwood Animal Clinic Montgomery County Pa Emergency Dispatch Ups Store Clifton Park Ny Comcast Make A Payment Is Redgif Safe Murphy's Loft Blakeslee Pa Spencer Breslin Green Dot Overdraft Protection Paused Two ambulances were called to a crash at a busy Dundee junction on Friday morning The collision involving two cars happened at East Dock Street at the traffic lights at the junction with East Marketgait The incident caused delays on several surrounding roads It has been confirmed no one was taken to hospital ended up quite a distance from each other on either side of the junction “Two ambulances were parked up near the scene I saw one leaving after checking a woman over “Two recovery trucks were also called to uplift the cars One driver said: “Traffic was very slow moving along Broughty Ferry Road and there were tailbacks up Blackscroft “It was much worse closer to the Olympia “The radio said there was a crash close to the lights A spokesperson for Scottish Ambulance Service said: “We received a call at 8.08am today to attend an accident on East Dock Street Dundee and we dispatched two ambulances to the scene.” Comments are currently disabled as they require cookies and it appears you've opted out of cookies on this site. To participate in the conversation, please adjust your cookie preferences in order to enable comments Here is the latest breakdown of scheduled and emergency works taking place across Hull over the next few weeks The dates displayed for an article provide information on when various publication milestones were reached at the journal that has published the article activities on preceding journals at which the article was previously under consideration are not shown (for instance submission All content on this site: Copyright © 2025 Elsevier B.V. Jenese Harris FREEZE WARNING IN EFFECT FROM 1 AM TO 9 AM EST SUNDAY FROST ADVISORY: ALACHUA, BRADFORD AND CLAY 1 AM TO 9 AM SUNDAY Sub-freezing temperatures as low as 30 are expected. FREEZE WARNING IN EFFECT FROM 1 AM TO 9 AM EST SUNDAY Temperatures will drop into the mid-30s, with calm winds shifting from north to northeast with mostly clear skies overall. Winds will shift more from the west in southeast Georgia. Rain is not in the forecast. Moisture from the Gulf of Mexico will help fuel some instability in the atmosphere Monday through Wednesday. A cold front moving through at the same time will swiftly push the more humid air out east by Friday. Average temperatures for this time of year are a high of 69 and a low of 47 degrees Fahrenheit. There is a low chance for rain Monday for southeast Georgia. There is a 50 percent chance for rain Wednesday all day as a cold front moves through the region. Copyright 2024 by WJXT News4JAX - All rights reserved. Veteran journalist and Emmy Award winning anchor Click here to take a moment and familiarize yourself with our Community Guidelines TV Listings Friday’s flood advisory, which won’t exprie until 6 a.m. on Saturday, is not what locals need after two consecutive days of local flooding throughout Southeast Georgia and Northeast Florida. As a third day of rain looms, Friday’s potential flooding could occur in the following areas: Coastal Nassau, Western Duval, Coastal Glynn, Coastal Camden, cities of Fernandina Beach, Dock Junction, Yulee, Jekyll Island, Amelia City, Glynn Haven, Normandy, Country Club Estate, Dover Bluff, Kingsland, Sea Island, Dungeness, and St. Simons Island. WATERWAYS: Once the rainfall begins it could impact rivers, creeks, streams, and other low-lying and flood-prone locations. TREES: Trees could topple as well due to saturated soil. WHY IS THIS HAPPENING?: These are not your typical afternoon storms. The atmosphere is filled with water vapor, a looming front and low pressure. A stationary front has caused excessive rain. This is typical of a stationary front. As long as it remains in an area it can slowly move, while creating multiple cycles or rain for days. Unlike a cold front, that can move through cause a line of storms and then bring cooler temperatures behind it, a stationary front is known for flash flooding due to excessive cycles of rain. The moisture in the atmosphere is equivalent to 2 to 2.6 inches. Multiple inches of rain could accumulate Friday from late morning through the evening. A 1951 graduate of Glynn Academy in Brunswick he entered Georgia Teachers College and graduated with a degree in English in 1958 Mandes became director of public relations for Georgia Southern College During his 27-year career at Georgia Southern Mandes’ leadership led to the creation of the office of Institutional Development which was a key component to the growth of the college "College Today," which was broadcast on several stations and Georgia Public Broadcasting Network he was an integral member of the team that re-established the football program and the hiring of Erk Russell as its first head coach Mandes authored five books: "Erk: Football Fans & Friends," "Attic of My Memory," "Life With Granny," "Life with Granny II" and "Off Stage." He was an active columnist for several newspapers and an essayist for the Atlanta Constitution he often drew inspiration from his days growing up with "Granny" in Dock Junction Upon his retirement from Georgia Southern College in 1988 he continued a rewarding marketing career working with Southeastern Marketing assisting seven technical colleges with fundraising and image enhancement he became the first editor of Statesboro Magazine and remained a contributor for the rest of his life Known to his grandchildren and many young people in the community as "Big Daddy," he was a constant encourager to his family and friends He was often sought for advice and wisdom and was a true mentor at heart resulting in the ability to help others achieve and attain their goals and dreams Jan Marie Page and Garrett Mandes (Faith); and three great-grandchildren The service will be held on at Joiner-Anderson Funeral Home in Statesboro Visitation will take place from noon until 2 p.m. followed immediately by the funeral service the family requests that donations be made to the Georgia Southern Athletic Foundation in memory of Ric Mandes at https://www.givecampus.com/campaigns/60955/donations/new Friends may sign the online register book at www.joineranderson.com Joiner-Anderson Funeral Home & Crematory of Statesboro is in charge of arrangements Sign the Legacy online guestbook at www.statesboroherald.com FREEZE WARNING: A freeze warning remains in effect from 11 p.m. Friday through the early morning hours of Saturday 9 a.m. The areas that will be impacted are below for Southeast Georgia and Northeast Florida, shaded in purple. Some areas of southeast Georgia could get as low as 26 degrees Fahrenheit and as low as 28 degrees Fahrenheit for inland counties in Northeast Florida. Wrap or drain or allow them to drip slowly. Bring sensitive plants indoors. Anyone unhoused should go to a shelter immediately. Pets should be indoors until temperatures in above 50 degrees. Temperatures will drop into the mid to low 30s for some inland counties of Northeast Florida and the mid-20s due to the wind chill for most of Southeast Georgia. Breezy winds from the afternoon will decrease at night between 5 and 10 miles per hour from the north with moderate humidity and mostly clear skies. The wind chill will make temperatures feel at least 5 to 8 degrees colder. Metrics details Hypoxia-inducible factors (HIF) 1 and 2 regulate similar but distinct sets of target genes Although HIFs are best known for their roles in mediating the hypoxia response accumulating evidence suggests that under certain conditions HIFs may function also under normoxic conditions Here we report that HIF2α functions under normoxic conditions in kidney epithelial cells to regulate formation of adherens junctions HIF2α expression was required to induce Dock4/Rac1/Pak1-signaling mediating stability and compaction of E-cadherin at nascent adherens junctions Impaired adherens junction formation in HIF2α- or Dock4-deficient cells led to aberrant cyst morphogenesis in 3D kidney epithelial cell cultures we show that HIF2α functions in normoxia to regulate epithelial morphogenesis It was proposed that HIF activation in VHL-deficient cancer cells promoted tumorigenesis by depleting E-cadherin from maturing AJs Whether HIF2α is involved in the regulation of E-cadherin levels and epithelial cell polarity in VHL-expressing kidney epithelium in normoxic conditions remains incompletely understood We show that HIF2α levels in normoxic conditions upregulate the mRNA and protein expression levels of a Rac1 guanine nucleotide exchange factor (GEF) Dedicator Of CytoKinesis 4 (Dock4) Dock4-mediated activation of Rac1 is needed to support the formation of polarized MDCK cysts Depletion of HIF2α or Dock4 in normoxia interfered with MDCK cystogenesis leading to formation of multilumen cysts This study identifies Dock4 as a novel mediator of HIF2α-driven activation of Rac1 signaling and shows that HIF2α expression in normoxia maintains basal Rac1 activity necessary for proper AJ formation and cystogenesis of kidney epithelial cells MDCK cells infected with a retrovirus containing an empty short hairpin RNA (shRNA) expression cassette were used as a control in all experiments Analysis using HIF2αKO#2 and #3 cells displayed a similar trend although the inhibitory effects were not statistically significant for all the targets (data not shown) our data suggests that HIF2α function is different from that of HIF1α as HIF2α appears to participate in the regulation of cyst morphogenesis also in normoxia Knockout of HIF2A disrupts morphogenesis of MDCK cysts in normoxic conditions (a) RT-qPCR analysis of the mRNA expression level of selected HIF target genes in 2D cultures of control and HIF2α-KO cell lines (#1 and #2 combined) under normoxic (N) and hypoxic (H **P < 0.001; *** P < 0.0001 (two-way ANOVA) (b) Control and HIF2α-KO MDCK cysts were grown in 3D under normoxia or hypoxia (48 h 1% O2) conditions At day 6 the cysts were fixed and stained for an apical membrane protein podocalyxin (green) A single confocal slice from the middle of the cysts is shown (c) Quantitation of the cyst phenotypes in control and HIF2α-KO MDCK cell lines grown as in (b) The percentage of cysts with single lumen was calculated and averaged from 4 to 8 independent experiments A minimum of 160 cysts per sample was scored in each experiment *P < 0.05; **P < 0.001 (Fischer’s exact test) Expression analysis of genes involved in EMT and AJs in HIF2α-KO MDCK cells (a) RT-qPCR analysis of the mRNA expression levels of genes encoding SNAI1 and Dock4 in control and HIF2α-KO#1 and HIF2α-KO#2 cell lines in normoxic conditions Relative expression levels are shown mean ± SD expression levels in control cells were normalized to 1 not significant (unpaired Student’s t-test) ZO-1 and β-Catenin in control and HIF2α-KO#1 and HIF2α-KO#2 cell lines in normoxic conditions (c) Quantitation of the Western blot data represented in b Data is shown as mean ± SD (n = 3) of the ratio of protein expression level in HIF2α-KO#1 and HIF2α-KO#2 cell lines relative to control *P < 0.05; ns not significant (unpaired Student’s t-test) our analysis revealed robust downregulation of both E-cadherin (CDH1) and Dock4 (DOCK4) in normoxic HIF2α-KO cells Knockout of Dock4 disrupts morphogenesis of MDCK cysts in normoxic conditions (a) Western blot analysis of Dock4 in control and the Dock4-KO#1 and Dock4-KO#2 MDCK cell lines in normoxic conditions (b) Control and Dock4-KO MDCK cysts were grown in 3D under normoxic conditions (c) Quantitation of the cyst phenotypes in control and Dock4-KO #1 and #2 MDCK cell lines grown as in (b) The percentage of cysts with single lumen were calculated and averaged from 4 to 8 independent experiments Dock4-KO#1 and Dock4-KO#2 MDCK cell lines in normoxic conditions (e) Quantitation of the Western blot data in d for E-cadherin Data are presented as mean ± SD (n = 3) of the ratio of protein expression level in the Dock4-KO#1 and Dock4-KO#2 MDCK cell lines relative to control *P < 0.05; **P < 0.001; ***P < 0.0001; ns not significant (unpaired Student’s t-test) It is thus possible that depletion of Dock4 perturbs cystogenesis by interfering with AJ maturation Knockout of Dock4 decreases EGF-induced Rac1/Pak1 activation Dock4-KO#1 and Dock4-KO#2 MDCK cells were serum starved for 24 h and stimulated with EGF (100 ng/ml) for 10 min and Rac1 activity was detected by G-LISA Rac1 activation assay (b) Rac1 protein levels were measured by Western blotting (c) Quantitation of Western blot data of (B) Rac1 protein level **P < 0.001; ns not significant (two-way ANOVA) (d) Western blot analysis for p-Pak1 and total-Pak1 following EGF stimulation is shown in control A representative blot of three independent experiments is shown (e) Quantitation of the data are shown as the ratio of arbitrary absorption units of p-Pak1 and Pak1 (mean ± SD) *P < 0.05; **P < 0.001; ns not significant (two-way ANOVA) HIF2α-KO#1 and HIF2α-KO#2 MDCK cells were serum-starved for 24 h and stimulated with EGF (100 ng/ml) for 10 min (g) Rac1 protein levels were measured by Western blotting (h) Quantitation of Western blot data of Rac1 protein levels as shown in g Data are presented as mean ± SD (n = 3) of the ratio of protein expression level in the HIF2α-KO#1 and HIF2α-KO#2 MDCK cell lines relative to control (i) Western blot analysis for p-Pak1 and total-Pak1 following EGF stimulation is shown in HIF2α-KO#1 and HIF2α-KO#2 MDCK cells and control cells (j) Quantitation of the p-Pak1 and total Pak1 levels are shown as the ratio of arbitrary absorption units of p-Pak1 and Pak1 (mean ± SD) Depletion of HIF2α and Dock4 expression affects formation of nascent cell–cell adhesion contacts HIF2αKO and DOCK4KO cells were seeded sparsely onto coverslips and grown for 48 h Rac1/Dock-inhibitor (ZINC69391) was added after the first 24 h when indicated After a total of 48 h cells were fixed and stained for E-cadherin (green) and ZO-1 (red) Maximum intensity projections of confocal z-stack images are shown (a,b) The arrows in b indicate the locations of for intensity histograms shown in (c) (c) The representative intensity histogram analysis of E-cadherin (green) with ZO-1 (red) from (b) (d) Quantification of the distribution of intensity peaks of E-cadherin in control DOCK4KO and ZINC69391-treated control cells Combined data from more than 20 images per sample is shown Five measurements were made from each maximum intensity profile Relative width of E-cadherin distribution is shown relative to that of untreated control (normalized to 1) Canonical HIF signaling is an important driver of renal cancers and it is thus possible that HIF2α activation is crucial for maintaining the hypoxia response signaling promoting cancer progression in the kidney In most other tumor types HIF2α might not be essential for growth and loss of HIF2α could directly promote tumorigenesis Further studies are needed to characterize the context-specific factors that determine the role of HIF2α in tumorigenesis a classical model to study cell polarization to address the role of HIF2α in kidney epithelia Using canine cell model is not without challenges we could not use established antibodies to detect human HIF2α since these did not cross-react with canine HIF2α human kidney organoid cultures have become a feasible alternative model It will be important to validate our results in such human organoid models in the future MDCK cells were cultured either in normoxic (16% O2 and 94% N2) conditions in an Invivo2 400 hypoxic workstation (Baker Ruskinn a selective inhibitor of Rac1 was reconstituted in dimethyl sulfoxide (DMSO) and used at a concentration of 100 µM The following antibodies were used: podocalyxin antibody (3F2/D8 cell line all corresponding secondary antibodies were purchased from Abcam (Cambridge Expression levels were normalized to TATA box binding protein The primary antibodies used were as follows Dock4 (ab85723 Confocal images were acquired at RT using an Olympus FluoView-1000 laser-scanning confocal microscope with 100 × UPlanSApo (NA:1.40) oil immersion objective (Olympus Sequential z-stack scans were performed using 405 nm 488 nm and 543 nm laser lines for fluorophore excitation coupled with DAPI (430–470 nm) GFP (505–525 nm) and Cy3 (560LP) emission filters For 3D morphology analysis at least 160 cysts per sample were analyzed and scored for presence of single central hollow lumen delineated in most sample sets by strong podocalyxin staining For some samples lumens were assessed using actin- (TRITC/Alexa488-Phalloidin) or ZO-1-staining Cysts with no or multiple small lumens were scored as abnormal For localization pattern analysis image stacks were deconvolved and analyzed using Huygens Professional software (Scientific Volume Imaging Five measurements of E-cadherin dispersion per each image maximum intensity projection were performed and their average from 20 or more cells was analyzed Representative images were collected with the FV10-ASW software (Olympus Japan) and imported into Adobe Photoshop CS (Adobe Systems Western blot bands were quantified using Image J Images were imported into Photoshop and CorelDraw for creation of figures To assess Rac1 activation Rac1 G-LISA kit (Cytoskeleton) was used according to the manufacturer’s protocol Cells were cultured first for 12 h in minimal essential medium (MEM) (Gibco) containing 5% fetal bovine serum (FBS Thermo Fisher Scientific) after which they were washed with PBS and cultured for an additional 12 h in MEM without FBS Then cells were washed with PBS and cultured for an additional 4 h in MEM without FBS with or without adding Rac1 inhibitor ZINC69391 to final concentration of 100 µM Then cells were washed with PBS and incubated for 5 min with EGF (Peprotech) at concentration 100 ng/ml Protein was isolated using standard G-LISA buffer GL36 (Tris pH 7.5 Obtained lysate was aliquoted and frozen in liquid nitrogen The Rac1 G-LISA kit (Cytoskeleton) contains a Rac-GTP-binding protein linked to the wells of a 96 well plate GTP-bound Rac1 in cell/tissue lysates will bind to the wells while inactive GDP-bound Rac1 is removed during washing steps The bound active Rac1 is detected with a Rac1 specific antibody The degree of Rac1 activation is determined by comparing readings from activated lysates versus non-activated lysates Plates were read in a Multilabel Counter 1420 VICTOR3V (Perkin Elmer Data are expressed as means ± SD of at least three independent experiments Comparative data were analyzed using the unpaired or paired Student’s t-test (two groups) two-way ANOVA (three or more groups) or Fischer’s exact test (cyst phenotype quantitation) Statistical significance is indicated with asterisks; * P < 0.05 The microarray data generated during this study has been deposited in the Gene Expression Omnibus database under accession number GSE121325 Oxygen sensing by metazoans: The central role of the HIF hydroxylase pathway The role of HIF in immunity and inflammation a transcription factor selectively expressed in endothelial cells Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma: HIF-2alpha promotes an aggressive phenotype Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation Pan-genomic binding of hypoxia-inducible transcription factors A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development a putative basic helix-loop-helix-PAS-domain transcription factor is closely related to hypoxia-inducible factor-1 alpha and developmentally expressed in blood vessels Loss of HIF-2α and inhibition of VEGF impair fetal lung maturation whereas treatment with VEGF prevents fatal respiratory distress in premature mice hypoxia-inducible expression of HIF-2α in distinct cell populations of different organs HIF-2α regulates Oct-4: Effects of hypoxia on stem cell function Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells Effects of CagA+ Helicobacter pylori infection on expression of HIF-2a and ABCG2 in human gastric cancer cell line SGC7901 under normoxia and hypoxia conditions ARNT-dependent HIF-2 transcriptional activity is not sufficient to regulate downstream target genes in neuroblastoma Hypoxia-induced epithelial-mesenchymal transition in cancers: HIF-1alpha and beyond HIF2α signaling inhibits adherens junctional disruption in acute lung injury Cell polarity as a regulator of cancer cell behavior plasticity Regulation of E-cadherin expression by VHL and hypoxia-inducible factor Organoids: A historical perspective of thinking in three dimensions Raykhel, I. et al. BAMBI is a novel HIF1-dependent modulator of TGFβ-mediated disruption of cell polarity during hypoxia. J. Cell Sci. https://doi.org/10.1242/jcs.210906 (2018) Generation of single and double knockdowns in polarized epithelial cells by retrovirus-mediated RNA interference Caveolin-1 is not essential for biosynthetic apical membrane transport Two distinct integrin-mediated mechanisms contribute to apical lumen formation in epithelial cells Gp135/podocalyxin and NHERF-2 participate in the formation of a preapical domain during polarization of MDCK cells Genome engineering using the CRISPR-Cas9 system The basics of epithelial-mesenchymal transition New insights into epithelial-mesenchymal transition in kidney fibrosis HIF2α cooperates with RAS to promote lung tumorigenesis in mice Snail1 mediates hypoxia-induced melanoma progression and ZEB1 in malignant progression of cancer Garcia, M. A., Nelson, W. J. & Chavez, N. Cell-Cell junctions organize structural and signaling networks. Cold Spring Harbor Perspect. Biol. https://doi.org/10.1101/cshperspect.a029181 (2018) The MDCK epithelial cell line expresses a cell surface antigen of the kidney distal tubule Characterization of two MDCK-cell subtypes as a model system to study principal cell and intercalated cell properties Dock4 forms a complex with SH3YL1 and regulates cancer cell migration Dock4 is regulated by RhoG and promotes Rac-dependent cell migration A Rac/Cdc42 exchange factor complex promotes formation of lateral filopodia and blood vessel lumen morphogenesis A brain serine/threonine protein kinase activated by Cdc42 and Rac1 Gomez, D. et al. Proapoptotic and antiinvasive activity of Rac1 small molecule inhibitors on malignant glioma cells. OTT https://doi.org/10.2147/OTT.S67998 (2014) Dynamic contacts: Rearranging adherens junctions to drive epithelial remodelling Beyond E-cadherin: Roles of other cadherin superfamily members in cancer Dynamics of adherens junctions in epithelial establishment Roles and modes of action of nectins in cell-cell adhesion Vertebrate Claudin/PMP22/EMP22/MP20 family protein TMEM47 regulates epithelial cell junction maturation and morphogenesis Campbell, I. D. & Humphries, M. J. Integrin structure, activation, and interactions. Cold Spring Harbor Perspect. Biol. https://doi.org/10.1101/cshperspect.a004994 (2011) Kannan, N. & Tang, V. W. Myosin-1c promotes E-cadherin tension and force-dependent recruitment of alpha-actinin to the epithelial cell junction. J. Cell Sci. https://doi.org/10.1242/jcs.211334 (2018) Tension-sensitive actin assembly supports contractility at the epithelial zonula adherens HIF-2α specifically activates the VE-cadherin promoter independently of hypoxia and in synergy with Ets-1 through two essential ETS-binding sites Hypoxia-inducible factors and the response to hypoxic stress The transcription factor EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction Cutting edge: Hypoxia-inducible factor 1α and its activation-inducible short isoform I.1 Negatively regulate functions of CD4+ and CD8+ T lymphocytes Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1 Genome-wide gene expression profiling revealed a critical role for GATA3 in the maintenance of the Th2 cell identity Genomic views of STAT function in CD4+ T helper cell differentiation Dock4 regulates dendritic development in hippocampal neurons Molecular association between β-catenin degradation complex and Rac guanine exchange factor DOCK4 is essential for Wnt/β-catenin signaling Actin-delimited adhesion-independent clustering of E-cadherin forms the nanoscale building blocks of adherens junctions Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism Download references Salmu and Riitta Jokela for overall expert technical assistance Jaana Träskelin for expert technical assistance at Biocenter Oulu Virus Core Laboratory and Dr Hang-Mao Lee for help in analysis of microarray data Imaging was performed at the Biocenter Oulu Light Microscopy Core Facility supported by Biocenter Finland This work was funded by the Academy of Finland Research Council for Health grants [114344 (JM) 263770 (AM)] and Academy of Finland Center of Excellence 2012-2017 grant (251314 to JM Faculty of Biochemistry and Molecular Medicine Extracellular Matrix and Hypoxia Research Unit JM; Validation: IR; Formal analysis: IR; Investigation: IR JM; Project administration: JM; Funding acquisition: JM which develops hypoxia-inducible factor prolyl 4-hydroxylase inhibitors as potential therapeutics The company supports research on hypoxia response signaling in the laboratory of JM Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41598-024-62955-7 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 Work on the A477 Nash Fingerpost junction between on the road between Milton and Pembroke Dock looks set to be completed earlier than expected. Traffic lights are being installed at the ‘treacherous’ junction, with campaigners long calling for safety and layout changes to the dangerous ‘black spot’ at the busy junction along the A477 to A4075. The North and Mid Wales Trunk Road Agency has stated today (August 9): “Although some testing and additional work is still required, the road will be open in both directions earlier than planned, by August 15 at 6am. “Please note that after the road reopens, permanent traffic signals and a 40 mph speed limit will remain in place to ensure the safety of the crossing. “There are still some elements of work to be completed but these are small-scale and localised. “This will require traffic lights to be re-installed at the junction after the bank holiday in September between 9.30am and 3pm. Further updates will be given closer to the time.” For more information, please visit: https://traffic.wales/current-projects/a477-nash-fingerpost-junction Comments Tel: 01834 843262[email protected]Follow us Further Links Owned or licensed to Tindle Newspapers Ltd. | Independent Family-Owned Newspapers | Copyright & Trade Mark Notice & 2013 - 2025 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. Here is the latest breakdown of scheduled and emergency works taking place across Hull over the next few weeks. All works are subject to change. DJ Mag gets the lowdown on London’s monstrous new multi-room, multi-purpose venue...   Last year was, at best, a mixed bag for London club culture. The capital lost yet more renowned venues in Dance Tunnel, Passing Clouds and Studio 338, and very nearly waved goodbye to the jewel in its crown, Fabric. Some respite was offered through that institution being saved and small new ventures such as The Bridge, but on the whole, we’re hoping 2017 will be a decidedly more positive year. What better way to kick things off then, than the launch of brand new mega-venue, Printworks London?  Launching on Saturday 4th February with a line-up that boasts Seth Troxler, The Martinez Brothers, Luciano and Loco Dice, Printworks’ first series offers a heavy-hitting but varied selection. Elsewhere nights are hosted by Snowbombing and UKF, Ben Klock, Maya Jane Coles, Hot Since 82, The Hydra, Melt Festival and more!  Situated in the Docklands area, the 5000-capacity structure is, as its name suggests, a converted printing press (formerly used to churn out the Daily Mail and Evening Standard — at least it’s finally been put to good use!), which will now host to a variety of cultural events across its six rooms. “It’s very difficult for a traditional nightclub to exist nowadays. The pressure to make a business out of two nights a week is enormously challenging,” explains Will Harold of LWE (Tobacco Dock/Junction 2 organisers and co-promoters at Printworks alongside Broadwick Live and operators The Vibration Group). “We might be a little bit bonkers taking it on but it's too exciting not to. You know it's a good space when you're in there and you're completely transported away from everyday life, and I really get that with Printworks.” The part that really has us excited here at DJ Mag is the Press Halls. At a whopping 100 metres long, the space will operate as the main room for a series of big name dance events organised by LWE, offering state-of-the art lasers and an L’Acoustics soundsystem (the same used at Junction 2). The Press Halls will also be complemented by an intimate second room. As with LWE’s Tobacco Dock, Printworks is also licensed for daytime events, allowing it to work in conjunction with other venues instead of competing against them. “We’ve tried to make every event unique and special,” says Will. “Adam Beyer is gonna play 10-and-a-half hours in the main room; Nina Kraviz is curating a bill — it’s been a challenging process getting the line-up right for her, and that’s not a negative thing! “She is enormously passionate about where she’s at musically at the moment. I think the end result is we’ve got a really exciting line-up that people definitely won’t expect.” It’s safe to say then, that London clubbers have a lot to look forward to in 2017. Watch our behind the scenes video of London’s Printworks below. Thrust Publishing Ltd, Unit 3, 30-40 Underwood Street, London, N1 7JQ, United Kingdom. Please enable JS and disable any ad blocker Rush-hour traffic was disrupted due to a traffic light failure at a busy Dundee junction on Monday morning Drivers were left “jostling” at the junction between East Dock Street and East Marketgait due to the broken lights Commuters in the city first reported the issue shortly before 8am on Monday The lights were down in all directions including the pedestrian crossings They were still broken at 10.30am but had come back on by 2pm One commuter who spoke to The Courier witnessed the chaos unfold just before 8am on Monday They said: “This is one of the busiest and most complex junctions in Dundee and never pleasant to navigate “I turn right from Dock Street to go up Marketgait lorries and buses from Marketgait were jostling to cross Dock Street to head towards the Bridge and Perth while traffic was heading in the opposite direction “Surely there must be a control centre where traffic light failures are flagged up Even a police officer or two could have made a difference “There are already lane restrictions on Dock Street and the failure of the lights only adds to the misery.” The issues come as drivers face 12 nights of overnight roadworks on the stretch of road between Gellatly Street and Broughty Ferry Road An Amey spokesperson said: “Issues with the traffic lights at East Dock Street which were reported early on Monday morning were caused by a damaged circuit board and have now been resolved “We urgently attend all reports of traffic signal outages to ensure they are fixed as quickly as possible and will continue to monitor the junction to ensure the signals operate safely.” Just completed is the third and final phase of the highly successful  £11m Bristol City Docks Capital Project to replace Bristol Floating Harbour’s 140-year-old Victorian lock system ensuring the future effective working of the docks and safeguarding the city from potential flood risks from the River Avon The scheme was carried out for Bristol City Council by BAM Nuttall Mr Matt Ewing, Project Manager at BAM Nuttall said: “The old lock system was a Victorian water hydraulic system which was unreliable and expensive to maintain. The improvements carried out in this project will ensure that the harbour has a reliable system that will last 100 years. on time and just below budget and the client is very happy There was a lot of concern from the client about the works affecting leisure craft using the harbour and impeding accessibility as well as the swing bridge works carried out affecting traffic flows However the project caused hardly any interruption in any of these areas.” The third phase (the smallest element of the scheme) involved replacing the manually operated oak gates at Netham Lock where boats from the River Avon gain access to the floating harbour Built in about 1809, Netham lock marks the end of the Feeder Canal. The lock gates here ensure that extreme high spring tides that come over Netham weir do not enter the city and that flood water from the River Avon is diverted over the weir. The scheme involved replacement of the lock’s four gates with new timber gates sympathetic to the historical nature of the location and designed to meet the standards of the latest Eurocode for lock gates which were specially made from Ekki hardwood timber – a sustainable timber for marine environments – and should last for at least 50 years were brought to Bristol by road and lowered into place by a 70-ton crawler crane In addition to the installation of the gates this phase included the refurbishment of the Underfall Yard sluice mechanisms The second phase involved upgrading the infrastructure of the entrance dock where the floating harbour meets the River Avon near the Clifton Suspension Bridge Managing the interface between new and Victorian engineering and construction techniques created a few challenges with Installing the new gates and ensuring they sealed being a major concern Start date : 08/04/2025 | End date : 16/06/2025 Work to carry out essential carriageway resurfacing to Neath River Bridge and Briton Ferry Dock Viaduct will commence on 08/04/2025 until 16/06/2025 Essential carriageway resurfacing will be carried out over a 10-week period under a full alternating eastbound & westbound carriageway overnight closures between the A48 Briton Ferry roundabout and A48 Earlswood junction Non motorway traffic To follow B4290 to rejoin A483 Swansea West.No HGV vehicles permitted past Edwards Works junction For further information, please contact Traffic Wales on 0300 123 1213 or via X or Facebook. Here is the latest breakdown of scheduled and emergency works taking place across Hull over the next few weeks. Notifications can be managed in browser preferences. We caught up with electronic music promoters LWE to talk about the role structures play in staging London's biggest events I would like to be emailed about offers, events and updates from The Independent. Read our Privacy notice The Royal Albert Hall has maintained a reputation as London’s premier concert venue for over a century Having hosted the biggest names in classical music since its opening in 1871 the 5,500 capacity venue is known primarily as the home of the BBC Proms and the Royal Choral Society Beyond this the stalls have witnessed some of the biggest names in popular culture: Frank Sinatra Coldplay and more recently the Arctic Monkeys The selectiveness of the halls directors have ensured that being chosen to play at the Albert Hall comes at the very height of an artist’s influence and success A landmark achievement in any musician’s career that the usual throngs of keen music goers entered the hall on a rainy evening in September greatly appreciating the irony that they were about to attend the historic halls first ever rave Who is responsible for bringing the techno heavyweights to Alby’ Hall? None other than London’s biggest underground event organisers LWE Though their repertoire is versatile ranging from corporate events to 10,000+ attendance shows LWE’s true hallmark is their canny ability to unearth architecturally stunning locations that other organisers would perhaps too nervous to approach “We’ve done everything in London in some shape or form” comments Paul Jack one of LWE’s founders: “but it’s an amazing thing to take what’s historically not a venue for electronic music and put a leading electronic label and artists into it.” Paul admits he looks for venues from a “ravers” perspective Having attended so many underground parties in his youth he professes that he got into event management due to the lacklustre nature of the damp claustrophobic clubs that electronic music has traditionally been consigned to “I got into it because dancing was always in dark sweaty rooms and I wanted to see it elevated to the next level the music is good deserves these concert venues.” “When you see it evolve onto such a world famous stage it’s so exciting Along with fellow founders Will Harold and Alice Favre with its first event being a warehouse party in Ewer Street Car Park featuring Detroit legend Carl Craig and have since become the driving force behind many large-scale electronic music events in the capital Throwing parties in well-established clubs such as Ministry of Sound they’ve also lent a helping hand to bring massive artists to infant venues such as The Fold and E1 (formerly Studio Spaces) In recent years though, their attentions have been focused on the jewels in their crown: their signature venue Tobacco Dock – a Grade I listed abandoned warehouse located in the East End, and since 2016 their very own festival, Junction 2 a techno extravaganza held in Boston Manor Park has been dubbed an “industrial utopia” and has attracted talent such as Carl Cox and Adam Beyer to play on its emblematic bridge stage “it’s one of the only sites in London where you feel like you’re in London” comments Paul “creating an environment that people can get lost in and get dirty is really the essence of what we’re trying to do” The Boston Manor Park venue combines both the industrial aspects of motorway bridges and pillars with the natural woodland and landscaped gardens “The location has given the festival its identity I think that’s an added bonus for most people They all come because they want to rave under the bridge.” For LWE the understanding that location makes a party is both a blessing and a curse: “Oh we can be too ambitious definitely” laughs Will Harold “we find these places I mean our key role essentially is finding these amazing locations and then finding a way to throw a party there… sometimes it’s impossible and we have to bow out we’ve come across these incredible venues and it’s been hard to let them go.” “But when you have the potential of thousands of people in a space you can’t just be thinking about how amazing it would be “It’s no longer about ‘well we could fit some strobes over there’ it’s like ‘well where are we going to make people queue for the toilet Is this going to cause noise complaints from the neighbours?’ you know this stuff is actually the make or break.” One such ambitious location is Tobacco Dock The former warehouse located on London’s Docklands was discovered by the team by mistake after wandering into it on their way home from the office “We used to be based right around the corner and we’d constantly passed this big black gate outside and one day we thought What greeted them was a beautifully preserved Grade I listed Victorian warehouse complete with intricate steelwork and balconies skylights – even a central courtyard complete with a Great Exhibition-esque iron-latticed bandstand how are we going to through a party in there then?” Similarly to Junction 2 on Boston Manor Park the draw for LWE was the juxtaposition between the industrial car park outside of Tobacco Dock and the beautiful Victorian stone work on the inside managing to discover the warehouse as it was changing ownership “We just happened to approach the new people as they were taking on the lease for it We suggested we could do music events and then a few months later the first event that took place there was an LWE show.” LWE quickly ran into the kind of problems associated with operating a monument such as Tobacco Dock The building wasn’t designed specifically for events and it meant the team had to deal with industrial building managers and explain the nuances of operating shows “A lot of it is based on the space of the room and its capacity” Paul explains “It’s a big challenge when you’re booking a big event you have to look at the programming and make sure the headliners aren’t all in one room – we have three large rooms yeah but if you have your whole audience trying to get into one it can be trouble.” The property is protected by its listed status requiring LWE to limit the impact they have on the structure which Paul explains is both advantageous in creating a unique experience for guests but also difficult at a production level “You can’t fix anything to the building Everything has to be supported away from the walls and our build times are longer and we have higher maintenance costs.” A space that comes with little beyond a roof means the promoters are forced to build the entire event from scratch before every event flooring and erecting a functional show in a short space of time There are challenges in that the doorways are narrows so we have to think about crowd flow to make sure everything is safe the Excel Centre and you just do want you wanted with it you wouldn’t create such an amazing experience and that’s the beauty of operating somewhere like this Join thought-provoking conversations, follow other Independent readers and see their replies Traffic lights will be installed at the ‘treacherous’ Nash Fingerpost Junction in Pembrokeshire going into this summer it has been confirmed. Campaigners have long been calling for safety changes to the dangerous ‘black spot’ - petitioning to try and force the Senedd and the Highways Authorities to reconsider the layout of the busy junction along the A477 to A4075. An horrific accident at the junction last year which resulted in the death of a young motorcyclist once again highlighted the need for urgent alterations to be made at the road. Senedd Member for Carmarthen West and South Pembrokeshire Samuel Kurtz has kept pressure on the Welsh Government to deliver the promised safety improvements to the Nash Fingerpost junction on the road between Milton and Pembroke Dock. Responding to a Written Question by Mr Kurtz seeking clarity on the progress of the long-awaited road improvements, the Welsh Government’s Deputy Minister for Climate Change Lee Waters has confirmed that work is underway and that the traffic signals will be in place by the end of July 2024. The response also set out the actions that have already taken place including new give way signage on the A4075 and temporary speed limit reductions to 40mph on the approach to the junction, which will be made permanent before the traffic lights are installed. Mr Kurtz said: “After the Welsh Labour Government promised long-overdue safety improvements to the Nash Fingerpost junction, I’m keen to ensure they stick to their word after years of false promises. “With works underway and a date for the completion of the traffic lights, I know this will be a great comfort to road users. It is just somewhat sad that this work comes off the back of an impassioned local campaign following a tragic death at the junction. “However, the success of the campaign to see these improvements is down to the tenacity of many local people who refused to take the Welsh Labour Government’s ‘no’ for an answer. “I am sure that they will join me in welcoming the news that the improvement work will be completed before the end of July.” Tel: 01834 843262[email protected]Follow us Owned or licensed to Tindle Newspapers Ltd | Independent Family-Owned Newspapers | Copyright & Trade Mark Notice & 2013 - 2025 Network Rail’s second round of public consultation to increase rail capacity through Ely opens today (Monday 24 May 2021) as part of a six-week consultation to gather feedback from the public on proposals being presented to upgrade the railway The aim of the Ely area capacity enhancement (EACE) programme is to upgrade the railway to allow more trains to run through Ely Increasing capacity will mean better connectivity and reliability for passenger services while meeting the demand for more rail freight between the Port of Felixstowe the West Midlands and the north to support sustainable Proposals and options are being presented to the public for the first time to upgrade the infrastructure at key sites in an area defined as Ely South that includes: • Proposed infrastructure changes to part of the Soham branch line and Ely Dock junction• Proposed changes to track and platforms at Ely station• Options to upgrade the nearby Stuntney Road bridge• Options to upgrade two bridges across the Great River Ouse adjacent to Ely marina• Proposal to close Kiln Lane level crossing with options to maintain pedestrian and vehicle access to the east side of the railway The feedback from this second round of consultation will help to progress designs prior to selecting preferred options and submitting a Transport and Works Act Order later in 2022 Owing to the ongoing Coronavirus situation, Network Rail is hosting the second round of public consultation via the Ely project webpage. The consultation documents are available to view and download from the consultation area of the Ely project webpage together with the online survey form to formally submit comments to Network Rail on the proposals being presented There will also be an opportunity for the public to put their questions to Network Rail’s project team via a live webchat facility or by calling the consultation hotline using the details below: The live webchats are available (access via the project webpage) from 25 May to 5 June 2021 at the following times:• Tuesday Thursday and Friday 10:00-16:00• Wednesday 14:00-20:00 The consultation phone line (0800 160 1780) is available from 25 May to 5 June 2021 at the following times:• Tuesday Thursday and Friday 14:00-17:00• Wednesday 17:00-20:00• Saturday 10:00-13:00 Hardcopies of the consultation booklet are available upon request by calling Network Rail’s 24/7 helpline number on 03457 11 41 41 or emailing: elyareacapacityenhancements@networkrail.co.uk Rail Minister Chris Heaton-Harris said: “This is a chance for passengers who use the rail network through Ely to have a say on how to deliver better connectivity and more punctual “I encourage people to engage with the consultation let us know your views on these proposed infrastructure improvements and help shape the future of your railway.” Network Rail’s route director for Anglia said: “Following a successful consultation in late 2020 which saw a lot of support for the principle of increasing capacity through Ely we are now in a position to present a number of options on how we can upgrade the railway to achieve these benefits It is so important to seek the views of the community who live and work in the Ely area Their feedback will help to inform our designs as we progress with this important project and I hope everyone who wants to will take the opportunity to have their say." A further public consultation is planned later in 2021 which will focus on proposals and options for the remodelling of the track layout at Ely North junction and level crossings across the Ely wider area More details on these future consultation rounds will be announced nearer the time Project webpage: www.networkrail.co.uk/Ely Follow us on Twitter: @networkrailANG using the hashtag #ElyRail to grow and expand the nation's railway network to respond to the tremendous growth and demand the railway has experienced - a doubling of passenger journeys over the past 20 years Powered by Bury Free Press, Suffolk Free Press, Newmarket Journal & Haverhill Echo Powered by Bury Free Press, Suffolk Free Press, Newmarket Journal and Haverhill Echo Home   Ipswich   News   Article The A14 near Ipswich which was closed in both directions following a police incident has reopened The carriageway between the Copdock Interchange It was closed for nearly five hours due to concerns for the safety of a female. Click here for full story. Two fire engines were also been called to the incident The westbound carriageway was closed from junction 58 The eastbound route was also shut and the closure was expected to be extended from junction 55