Log in via email All your bookmarks will be available across all your devices Password must be 8 characters long including one capital letter Please confirm your email address and we’ll send you a link to reset your password Single account access for STIRworld.com,STIRpad.com and exclusive STIRfri content Verification link sent to check your inbox or spam folder to complete sign up process or opt for the best experience by closing this banner For more detailed information please read our Privacy Policy The Dutch artist and designer is set to present her new collection of tapestries and pendants at the upcoming Dutch Design Week 2023 by Anushka SharmaPublished on : Oct 17 she collaborates with the TextielMuseum and Glass Museum She also processes residual pieces of wood and recycled concrete into one-off pieces The sustainability landscape as well as the reminiscent visions of Keja-Planken implore observers to delve deep, into encountering their own awareness. Through each collaboration, the product designer dissects new worldly aspects and her responses to them the designer depicts how the state of mind shifts constantly Her vivid entities invite you to engage rather than just look at them; ultimately universe and life forms,' are an appeal for “open-mindedness They are meant to be hopeful,” the designer concludes Try holding a plank for 10-30 seconds if you are a beginner It's important to focus on proper form rather than how long you can hold a plank Gradually work your way up to 60 seconds as your core strengthens Planks can strengthen your core and tone your muscles, but you cannot target belly fat with a plank You can perform planks as part of a regular exercise regimen that includes cardiovascular and strength training to lose belly fat It's also important to eat a nutrient-rich diet It's common and normal to shake when you are planking, especially if you are new to exercise. Shaking happens if your muscles fatigue during exercise You may notice that you shake less as you build strength American Council on Exercise. Ab Exercises - Front Plank Chevidikunnan MF, Al Saif A, Gaowgzeh RA, Mamdouh KA. Effectiveness of core muscle strengthening for improving pain and dynamic balance among female patients with patellofemoral pain syndrome Calatayud J, Casaña J, Martín F, Jakobsen MD, Colado JC, Andersen LL. Progression of core stability exercises based on the extent of muscle activity MedlinePlus. Muscle cells vs. fat cells Güsgen C, Willms A, Schaaf S, Prior M, Weber C, Schwab R. Lack of standardized advice on physical strain following abdominal surgery Shoulder pain: Learn more – shoulder pain: What helps? Institute for Quality and Efficiency in Health Care (IQWiG); 2024 Cooper DB, Yang L. Pregnancy and exercise MedlinePlus. Carpal tunnel syndrome MedlinePlus. Healthy habits for weight loss American Council on Exercise. 7 Benefits of Heavy Resistance Training Dry January is growing in popularity in the Netherlands, with some extending the challenge to Dry July and Sober September. Researchers and participants agree that the initiative often leads to a reduction in alcohol consumption, both short-term and long-term, EenVandaag reports. According to Bart Takkenberg, a gastroenterologist at Amsterdam UMC, the healthiest option is to avoid alcohol entirely. "There is no safe lower limit for alcohol consumption," he said. The Dutch Health Council’s 2015 guidelines recommend limiting alcohol intake to one drink per day but do not explicitly discourage consumption new scientific research may lead to a more restrictive advisory in 2026 "The idea of a ‘healthy glass of wine’ is likely to be dismissed." Dutch adults consume seven drinks per week A small percentage—6.7 percent—drink excessively with men consuming more than 21 drinks weekly and women more than 18 reported that participants in the challenge average 18 drinks per week before starting Founded in 2014, IkPas has grown steadily. In 2025, 13,442 people officially participated, but the movement extends beyond registered participants. "It's becoming a national phenomenon," Planken said. Among the 1,800 members of the EenVandaag Opinion Panel who participated in Dry January Common improvements included increased energy Mental clarity and mood enhancement were also frequently mentioned "I have more energy and don’t experience the usual 'blue Monday' feeling after weekends," one participant noted About 65 percent of participants successfully abstained from alcohol for the entire month while 32 percent did not complete the challenge Social occasions and stress were the most common reasons for breaking abstinence I extend Dry January into February or even March," one participant said Planken emphasized that most participants do not revert to previous drinking habits immediately "They have spent the month actively reflecting on alcohol consumption and feel it would be a waste to go back to old habits." Fifty percent of those who completed Dry January plan to drink less, while 10 percent intend to quit alcohol entirely. However, 32 percent expect to resume their previous drinking patterns. "For me, cutting back is harder than quitting for a month," a participant said. "I sometimes consider stopping completely "The market for 0.0 percent beverages has expanded rapidly in recent years," Planken said. However, he warned that non-alcoholic beer might reinforce associations with alcohol Choosing soda or juice instead might help break the psychological link." alcohol remains a major societal issue that needs continued attention." The insolvency proceedings affect around 40 employees in six branches: two on the Mannheimer Planken two in Baden-Baden and one each in Heidelberg and Karlsruhe Seppel is the second generation to run the stores for high-quality women's and men's shoes According to the provisional insolvency administrator Sandra Wirtz the application has been filed for the sole proprietorship "Schuhsalon Leone online trading and the aftermath of Corona are putting increasing pressure on the entire shoe trade," says the provisional insolvency administrator as reasons for this step Large parts of the shoe trade are in crisis due to the consequences of the Corona pandemic and the sharp rise in material prices "Consumer reluctance and the correspondingly lower demand from retail customers in addition to the months-long Planken renovation in Mannheim had a significant impact on sales and liquidity," Seppel is quoted as saying in a statement Wirtz says he has already gained an overview of the situation "Business operations are continuing without restrictions at all locations." The wages and salaries of the approximately 40 employees are secured until the end of September through insolvency benefits from the Federal Employment Agency "The priority is to further stabilize ongoing business operations and to explore all options that can enable a viable future solution for the company and its employees Exploratory talks have also been and are being held with suppliers and landlords," said the Mannheim-based insolvency lawyer Seppel had only opened a new “Gero Mure” branch on the Planken The shoe shop had already been located in P 6 for 20 years before moving away ten years ago We always keep you up to date: with our free newsletter SHOEZ compact You will regularly receive all information from the shoe industry in a clear form when a new magazine is published US Managing Director Peter Sachs hands over to Lance Taylor Alchemy plans to take over almost half of the Austrian shoe retailer Second best financial year in the company's history Creditors' meeting decides against P&C's takeover offer Sanela Krisat becomes International Sales Director sales representatives and business partners throughout the DACH association Telephone: +49 (0) 6 41 / 7 95 08 – 0Fax: +49 (0) 6 41 / 7 95 08 – 15Email: info@shoez.biz Designed by willsch-media.de Issues with signing in? Click here Need help signing in? A loan from six banks funded the €880m purchase of offices for a retrofit project without a lease PERE Seoul Forum PERE Tokyo Forum PERE Europe Forum 10-11 June 2025London Marriott Hotel Grosvenor Square London PERE America Forum PERE Asia Summit View all events > Your email address is already registered with us. Click here to receive a verification link and login. Don't have an account? Click here to register Please check your spam or junk folder just in case At least one person was killed and several others injured after a car drove into a crowd of people in the western German city of Mannheim A black SUV drove at high speed into people knocking over several pedestrians in Planken the main shopping street in the city of around 300,000 local outlet Mannheimer Morgen (MM) reported Kenneth “Ken” Buckland was not the director of Planning and Community Development for Wareham he was a part of the consulting team that helped develop plans for the downtown The intention was to revamp the streetscape but there was still much to be done and Wareham was in need of a town planner had thought he was through with public work and had been in the private sector for some time Town Administrator Derek Sullivan took him out to lunch and made an offer he “couldn’t refuse.” Accepting the position Buckland saw lots of potential and opportunity in Wareham that excited him this was a “full circle” moment as he was going to be able to oversee the implementation of a plan he had been a part of creating over a decade prior Buckland said he and the town administration shared a common goal: economic development Buckland’s status as the part-time town planner would change when Sullivan proposed a new position that combined the duties of a planning director and community and economic director The goal was to streamline how officials plan for the future by having Buckland answer directly to Sullivan Almost eight years later, Sullivan announced at a Tuesday, Jan. 9 Select Board meeting that Thursday, Feb. 29 will be Buckland’s final day as he is ready to retire he would like to continue on in an advisory role with the Redevelopment Authority and finally see his plans come to fruition — that would be when he’s not spending his time creating children’s books for his grandsons Buckland said he enjoys writing and illustrating his grandchildren into the books and plans to do more of it in his retirement but does not intend to publish the stories The latest one follows “Max the Turtle” who is searching for places to play This was inspired by the turtle costume his grandson received for Halloween Buckland came into this role with approximately 35 years of experience Buckland began his career studying environmental science specifically researching the land and water resources for a river in Connecticut Buckland said during that time he realized it would be beneficial to know land-use management as that is “what was having the biggest effects on the river.” Therefore he went and obtained his second master’s degree in environmental policy He would go on to hold a few positions before becoming the town planner for Falmouth Buckland said he got “bogged down in the local politics” and turned to private consulting before breaking back into the public sector in Wareham Buckland said he had a new perspective on politics “It’s the politics that is what makes things happen and you have to accommodate different directives and different needs,” he said Buckland said there were a number of projects and initiatives he enjoyed working on during his time in Wareham negotiating with cannabis businesses and obtaining many grants He said the grants he has been able to acquire do the work of advancing “different development opportunities” and also “gets people moving and investing in their properties.” During his time in office, Buckland said the town has been able to find developers for the Tremont Nail Factory, the Eastern Bank and other properties in Wareham Village Buckland said he’s “pleased” with his work in obtaining town funds from cannabis tax dollars and sales: “That was something that was controversial but it turned out rather benign and has raised [approximately] $4 million for the town.” The same year Buckland began working in Wareham the state legalized the sale of marijuana for recreational use Although some were hesitant toward welcoming these businesses Buckland saw the benefits it could have for the community Buckland said he had played a part in connecting developers with the right properties for them and negotiating the community host agreements while assisting the businesses with the permitting and processes He said he played a role in getting the Spring 2023 Town Meeting to approve the rezoning of Wareham Village “believing that something better could be done with the buildings and properties in the downtown and with proper land-use regulations in place.” The changes — which intended to promote more development while also preserving the character of the village — included new uses taller buildings and even buildings using the air rights over Merchants Way not all of the town's planning and development initiatives have had the full support of the community Buckland highlighted how community members disapproved of different solar projects over the last decade He said the town has solar on roofs and over parking lots but it was when the panels were going to be placed in open fields or green spaces that seemed to “bother people to no end.” He said this type of use was “fairly benign” and people are limited in what they can do when they do not own the land Buckland also said he found it challenging to represent the plan to bring in a casino, horse racetrack and hotel complex to town when he wasn’t in full support of the plan himself Approximately 1,000 voters showed up to the Spring 2021 Town Meeting at Spillane Field with over 800 votes cast not in favor of a large section of Wareham being rezoned as a “hospitality district.” The effort to rezone the land was led by the Notos Group — a family-run development company that initially pitched a slot parlor and racetrack before withdrawing those plans “I felt that although it made a lot of sense in terms of economic development and the amount of money the town would get from the development project and … from fees to the town would be enormous the impact on the commercial development and the village center could be significantly harmful to those areas as well,” he said “It wasn’t necessarily something I felt strong about but I did have to represent [it] because it did have an opportunity for the town to make some significant income.” Buckland gained some wisdom to pass down to his successors: “Listen to the people in the town because they know what works best for the community They have it in their hearts for the best outcome.” “Do your best to accommodate new money coming in and private investment that you can expect to occur in town,” he added but know they are probably right in their assessment of what works with the town.” Buckland said it may also be beneficial for the town to consider combining its water districts in the future as there would be “some cost savings associated with that.” “This has been a very good experience — very interesting “It’s a different kind of town than a lot of the ones around and it has a different demographic and a different attitude and I think that's good,” he added “It's refreshing and I think the town is going to do well for itself.” At least two people were killed and several others were seriously injured when a German man drove a vehicle into a crowd of people in the western  city of Mannheim Mannheim has a population of 326,000 and is about 52 miles south of Frankfurt In statements posted on social media Mannheim police confirmed an ongoing operation after “a 40-year-old suspect drove a car into a group of people who were in the Planken area of Mannheim city center Two people were killed and five seriously injured.” Police stated they “were able to arrest the 40-year-old German suspect from Rhineland-Palatinate [about 90 miles from Mannheim]” They said “at the current stage of the investigation it is not assumed that there is a political background” to the incident The incident came as crowds gathered in cities across Germany for parades to mark the Christian Carnival season on what Christian Germans mark as Rose Monday the highlight of their carnival season that takes place on Shrove Monday before the Lenten period begins on Ash Wednesday Video footage from the Planken shopping district area near Paradeplatz Square in the center of Mannheim showed shoppers standing outside an area cordoned off by police tape and strewn with debris Police have not said if the driver under arrest deliberately plowed into the crowd or whether it was accidental Editorial credit: Robert Buchel / Shutterstock.com The leading authority for the Architecture & Design community Recharge in a Restored Spanish Farmhouse in Menorca and Sean Carney—will draw on their expertise to offer insights on design trends and the future of healthcare environments.  who normally host their graduation show—one of the world’s most influential exhibitions of work by new designers—during Dutch Design Week Here are 15 of our favorite finds from the event Inert Domestic System by Célestine Peuchot at Design Academy Eindhoven Célestine Peuchot’s graduation project investigates the manufacturing processes behind the objects that occupy our daily living spaces exploring the tensions and relations between techniques and aesthetics in mass production and craft manufacturing A series of machine-objects function as elements of a fictional production chain that has inexplicably stopped Teunland by Teun Zwets at Design Academy Eindhoven Instead of embracing conceptual design, these interior items celebrate the practical or tied together to build objects as needed The focus lies on usability instead of refinement leading to a new aesthetic that questions our throwaway society Mementum by Baptiste Comte at Design Academy Eindhoven By imagining clay urns as ‘skins,’ Baptiste Comte finds a natural way to commemorate the memory of an individual and their fading tangibility as they return to the earth every biomorphic cylinder is different and recalls the uniqueness of each person The Lips by Sandra Keja Planken of Studio Noun Ceramic Totems by Kiki van Eijk of Kiki & Joost The relationship between hands and clay is the basis of the ceramic art form. The totems produced with Cor Unum are expressions of dedication—the investment of time Interlocking Planters by Joost van Bleiswijk of Kiki & Joost In a time where merging outdoors with indoors is more vital than ever, Joost designed a series of sculptural steel planters with playful forms for both inside and outside use Kunst-S by Lisanne Kamphuis At the Materialized exhibition, Kamphuis shows the hidden beauty of plastic waste in the form of vases made out of more than 600 Ferrero Rocher candy plastic wrappers utilizing a unique process she developed in her graduation year The designs give plastic waste qualities that are similar to high-end classic materials such as stone Raw Color’s Planum by Kvadrat A knitted upholstery textile with a smooth, soft surface serves up subtle matte luster and a natural, dry handle. Raw Color looked to 3D objects to create their versatile color scale before making a final selection of 20 tones from 350 hand-painted samples Pleated Pattern by Rebecca Hult Lamberger The designer’s graduation collection (showing in the collective EXI(S)T exhibition with eight other students from the Swedish School of Textiles) consists of printed textiles where surface patterns and pleating have been combined and the textile changes appearance as a result Viewers are motivated to interact with the textile and move around it Cosmic Coral by Yaroslava Galayko The base of the coffee table Cosmic Coral is made of recycled low-pressure high-density HDPE polyethylene in granules The sculptural table frame is formed by spot heating and then layering the material the base does not have any additional binders making it Cradle-to-Cradle recyclable The Dutch Design Week ambassador’s reflection of the vast emptiness resulting from the pandemic lockdown lead to a double exhibition between Kazerne and Van Abbemuseum showing pensive work from the collections of Edelkoort and the museum The works express a feeling of melancholy carried by humor and distance to the subject Virtual Tactility by Sabine Marcelis The virtual visitor gains control over a number of cameras placed in Victor Hunt Gallery in order to experience the designer’s new physical work from A to Z Piet Hein Eek’s Dutch Design in 40 colors by Lacq Metrics details Repetitive elements (RE) constitute the majority of the human genome and have a range of functions both structural and regulatory on genomic function and gene expression RE overexpression has been observed in several neurodegenerative diseases consistent with the observation of aberrant expression of RE posing a mutagenic threat Despite reports that associate RE expression with PD no study has comprehensively analysed the role of these elements in the disease This study presents the first genome-wide analysis of RE expression in PD to date Analysis of RNA-sequencing data of 12 PD patients and 12 healthy controls identified tissue-specific expression differences and more significantly differential expression of four satellite elements; two simple satellite III (repName = CATTC_n and _GAATG_n) a high-copy satellite II (HSATII) and a centromeric satellite (ALR_Alpha) in the blood of PD patients In support of the growing body of recent evidence associating REs with neurodegenerative disease this study highlights the potential importance of characterization of RE expression in such diseases Repetitive DNA classes in the human genome The major class of RE are Transposable elements which can be further divided into DNA transposons or Retrotransposons according to there mechanism of transposition Retrotransposons are the most abundant class in the human genome and can be further divided into long terminal repeats (LTR) and non –LTR retrotransposons Non-LTR elements have the ability to mobilise and can be further subdivided into SINE (e.g The LTR class of RTE contains endogenous retroviruses (ERVs) such as HERV-K To gain novel insight into the expression of all classes of RE unlike other methods that focus only on RTN we utilized the well-established RepEnrich pipeline that quantifies all known RE class sequences We report that overall REs are widely expressed in both tissues with observed tissue-specific differences and most significantly that two simple satellite III (repName = CATTC_n and _GAATG_n) a high-copy satellite II (repName = HSATII) and a centromeric satellite element (repName = ALR_Alpha) were differentially expressed in the blood in PD Mapped repetitive element expression in the blood and skin Analysis of RNA-Seq data from the blood of 12 PD patients and 12 controls (with an average of 24 (blood) or 31 (skin) million reads per individual) identified 20% of reads mapping to the reference genome GRCh37/hg19 aligned to the custom built RE psuedogenome assembly used in RepEnrich Of the reads that mapped to the RE pseudogenome assembly in the blood on average 37.10% originated from LINE elements In the skin on average 35.71% originated from LINE elements 9.41% from DNA and 0.57% other (satellite snRNA At the family level, 3 RE families were significantly differentially expressed at FDR ≤ 0.01; satellite, centr and acro (FDR = 7.88E-06, 7.88E-06, 6.39E-04 respectively), which were upregulated with a logFC increase of 2.05 for satellite, 1.84 for centr and 1.30 for acro in the blood from the PD patients (Supplementary Table 4) Upregulation of Satellite elements in the blood of PD patients At the subfamily level four satellite class repetitive elements were significantly differentially expressed at FDR ≤ 0.01 two simple satellite III (repName = CATTC_n and _GAATG_n) a high-copy satellite II (repName = HSATII) and a centromeric satellite (repName = ALR_Alpha) all of which were upregulated in the blood of PD patients Simple satellite III repeat (CATTC)n RNAs were the most significantly upregulated in the blood of PD patients (p-value = 2.27E-12) with a logFC increase of 4.40 Pericentromeric human satellite II (HSATII) repeat derived RNAs were significantly upregulated (p-value = 2.79E-12) with a logFC increase of 4.12 Simple satellite III (GAATG)n derived RNAs were upregulated in PD (p-value = 1.68E-11) with a logFC increase of 4.23 human alpha centromeric satellite (ALR_Alpha) derived RNAs were also upregulated in PD (p-value = 5.20E-08) with a 2.02 logFC increase are significantly differentially expressed Although the simple satellite III RE (repName = _GAATG_n) was also significantly upregulated there is a paucity of information available for the function of this RE in the literature in addition to increased expression levels a considerably small degree of variability was observed in the PD patients compared to the healthy control subjects This could hint at a yet undetermined regulatory process that can be associated with PD pathophysiology Therefore our data indicates that overexpression of these specific satellite elements is a potential disease-specific signature in the blood for PD and highlights the need for further characterization of our model in a larger data sets to also address if there is possible association with progression of the disease We set out to characterise RE expression with previously published PD RNA-Seq data in response to recent studies that have associated RTE expression with neurodegenerative disease This type of analysis has not been explored previously mainly due to the lack of technology to do so Using a tool that not only quantifies RTE expression but all class of REs we report that a group of satellite elements are differentially expressed and appear to have a PD specific expression signature in the blood Although we report the first genome-wide analysis of RE expression in PD to date our study does have a number of limitations we acknowledge that the cohort size (n = 24) is particularly small By showing that there are significant disease-specific signatures of RE expression we hope to illustrate that RE expression should be addressed when larger PD expression data-sets are available Another limitation is that we show through of our analysis (of the blood and skin of the same individuals) that RE expression occurs in a tissue specific manner Thus we cannot make any presumptions that this reflects what could be happening in the brain addressing RE expression in the brains of PD individuals is particularly problematic as the areas of interest will have occured alot of cell-death at time of post-mortem Despite the literature suggesting a possible role of RTE in the brain and neurodegeneration in particular the purpose of our present study was to look for possible differences in RE expression in readily available tissue (such as blood and skin) as a possible biomarker Further characterization is required to determine the consequence of upregulation of satellite elements in PD however our data supplies a potential novel non-invasive biomarker of the disease and its progression The median disability score assessed by the Schwab and England Activities of Daily Living Scale (SE-ADL) was 80% (ranging from 40% to 100%) None of the PD patients were current smokers and two had a history of smoking in the past The study was approved by the Research Ethics Committee of the University of Tartu Volunteer PD patients and healthy controls were recruited from the Department of Neurology and Neurosurgery at the University Hospital of Tartu A signed informed consent was acquired from all subjects participating in this study The venous blood of all study subjects was collected into Tempus Blood RNA Tubes (Thermo Fisher Scientific Inc The RNA was extracted applying Tempus Spin RNA Isolation Kit (Thermo Fisher Scientific Inc USA) combined with DNase treatment (RNase-Free DNase Set according to the manufacturer’s’ protocols The globin mRNA was removed from the extracted total RNA using GLOBINclear Kit for human (Thermo Fisher Scientific Inc one 4 mm punch-biopsy specimen was taken from non- sun-exposed skin of each subject from both study groups All biopsy specimens were instantly frozen in liquid nitrogen and stored at −80 °C until RNA extraction Biopsies were homogenized with Precellys24 homogenizer with the Cryolys system (Bertin Technologies) Germany) was used for total RNA extraction During the purification on-column DNase I treatment was performed (Qiagen Hilde The RNA quality was assessed using Agilent 2100 Bioanalyzer with the RNA 6000 Nano kit (Agilent Technologies) and the quantity was evaluated with Qubit fluorometer and Qubit RNA HS Assay kit (Life Technologies) The study samples RIN ranged from 6.7–9.5 in the blood and skin samples 50 ng of each RNA sample was amplified with Ovation RNA-Seq System V2 Kit (NuGen Technologies Inc USA) and the output double stranded DNA was used to prepare SOLiD 5500 W System DNA fragment libraries according to manufacturer’s protocols (Thermo Fisher Scientific Inc and 12 libraries were pooled prior to sequencing the SOLiD 5500 W XL with paired-end chemistry (75 bp in forward and 35 bp in reverse direction) in 6-lane mode was applied In the case of blood samples SOLiD 5500 W XL platform with fragment sequencing chemistry (75 bp in forward directions) in 3-lane mode was used In both cases approximately 40 million mappable reads were expected per one sample which is enough for successful whole transcriptome expression pattern analysis Raw color-space reads were filtered for rRNA The remaining reads were aligned as single-end reads to the GRCh37/hg19 reference genome while allowing multi-mapping to detect reads aligning to possible repeat sequences To ensure secondary alignments were reported in the BAM files no mapping quality cut-off was set LifeScope software (LifeTechnologies) with recommended settings designed for color-space read alignment and analysis was used for both mapping steps To connect color-space mapping with the RepEnrich pipeline https://github.com/nskvir/RepEnrich14 the GRCh37/hg19 mapped BAM files were parsed using samtools and in-house perl scripts to separate unique and non-unique mapped reads only alignments with MAPQ ≥ 10 (in Phred scale) were retained on average ~77% of all reads mapped to the reference genome the base-space sequence was inferred from the longest alignment and these reads were converted to FASTQ format This enabled us to convert the color-space data into suitable format for downstream analysis RepEnrich with default parameters was applied to obtain read counts of REs RepEnrich aligns multi-mapping reads separately to a pseudogenome containing the RE loci lifted from the RepeatMasker GRch37/hg19 Library in order to more accurately infer read counts which reflect the abundance of expressed RE RNA-Sequencing data was obtained from blood and skin of 12 PD patients and 12 healthy controls A RE pseudogenome assembly was constructed by concatenating the genomic sequence for the 1117 RE elements from the ReRCh37/hg19 Library Reads were mapped using the RepEnrich pipeline and differential RE expression was identified following EdgeR analysis The study was conducted in accordance with the Declaration of Helsinki and approval was granted by the Tartu University Ethics Committee Informed consent was obtained from all patients and controls The data supporting the conclusions of this article and raw counts from the RepEnrich output are included within this article and its supplementary information What Genetics Tells us About the Causes and Mechanisms of Parkinson9s Disease Progress in unraveling the genetic etiology of Parkinson disease in a genomic era Biology of Parkinson’s disease: pathogenesis and pathophysiology of a multisystem neurodegenerative disorder Neurochemistry and the non-motor aspects of PD A ‘bird’s eye’ view on the current status and potential benefits of blood biomarkers for Parkinson’s disease Management of non-motor symptoms in advanced Parkinson disease Delineating nonmotor symptoms in early Parkinson’s disease and first‐degree relatives Nonmotor Features in Parkinson’s Disease: What Are the Most Important Associated Factors Unbiased Approaches to Biomarker Discovery in Neurodegenerative Diseases Blood Transcriptomic Meta-analysis Identifies Dysregulation of Hemoglobin and Iron Metabolism in Parkinson’ Disease Looking beyond the brain to improve the pathogenic understanding of Parkinson’s disease: implications of whole transcriptome profiling of Patients’ skin Analysis of blood-based gene expression in idiopathic Parkinson disease Transcriptional landscape of repetitive elements in normal and cancer human cells Roles for retrotransposon insertions in human disease Identification of active loci of a human endogenous retrovirus in neurons of patients with amyotrophic lateral sclerosis Tau Activates Transposable Elements in Alzheimer’s Disease Krug, L. et al. Retrotransposon Activation Contributes to Neurodegeneration in a Drosophila TDP-43 Model of ALS, https://doi.org/10.1101/090175 (2016) Retrotransposition is associated with genome instability during chronological aging The prevalence of human endogenous retroviruses in cerebrospinal fluids from patients with sporadic Creutzfeldt–Jakob disease Retrotransposon activation contributes to fragile X premutation rCGG-mediated neurodegeneration Increased l1 retrotransposition in the neuronal genome in schizophrenia Pathogenic tau-induced piRNA depletion promotes neuronal death through transposable element dysregulation in neurodegenerative tauopathies Engrailed homeoprotein blocks degeneration in adult dopaminergic neurons through LINE‐1 repression The regulated retrotransposon transcriptome of mammalian cells Demethylated HSATII DNA and HSATII RNA Foci Sequester PRC1 and MeCP2 into Cancer-Specific Nuclear Bodies Transcriptional landscape of human endogenous retroviruses (HERVs) and other repetitive elements in psoriatic skin Pericentromeric satellite repeat expansions through RNA-derived DNA intermediates in cancer Accumulation of small murine minor satellite transcripts leads to impaired centromeric architecture and function Giordano Metal (2008) Transcription of satellite III non-coding RNAs is a general stress response in human cells SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson’s disease Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): Scale presentation and clinimetric testing results Website. Available at: R Core Team (2013). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, http://www.R-project.org/ Download references This work was supported by funding from the University of Liverpool and University of Tartu PhD scholarship (KB) IUT20-46 from the Estonian Ministry of Education and Research (SK) the TransGeno project in Tartu University under European Union’s Horizon 2020 research and innovation program under grant agreement No 668989 (SK) PUT1239 from the Estonian Research Council (PT) IUT2–4 from the Estonian Research Council (PT AP) and grant No 3.2.1001.11-0017 of the EU European Regional Development Fund (PT Billingsley and Freddy Lättekivi contributed equally Department of Molecular and Clinical Pharmacology Perron Institute for Neurological and Translational Science - library preparation and sequencing and manuscript writing - initiators and leaders of the study and data generation and manuscript writing All authors read and approved the final manuscript The authors declare no competing interests Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41598-019-40869-z Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily. MANF and CDNF levels were measured from serum samples of 34 PD patients and 35 controls using validated in-lab-designed enzyme-linked immunosorbent assay (ELISAs). MANF and CDNF mRNA levels in whole blood samples of 60 PD patients and 30 controls were measured by quantitative real time polymerase chain reaction (qRT-PCR). MANF concentrations in different blood cell types were measured by ELISA. Circulating MANF concentrations were significantly higher in PD patients compared to controls (P < 0.001) and were positively correlated with Beck Depression Inventory (BDI) depression rating. MANF protein was present in blood cells, however, MANF mRNA levels in the blood did not differ between PD patients and controls (P = 0.44). The mean concentration of serum CDNF was 33 pg/ml in the controls. CDNF levels were not altered in PD patients (P = 0.25). MANF but not CDNF level was increased in the blood of PD patients. It would be interesting to examine the blood level of MANF from early stage PD patients in future studies to test whether MANF can be used as a clinical marker of PD. Volume 13 - 2019 | https://doi.org/10.3389/fnins.2019.00929 Background: Mesencephalic astrocyte-derived neurotrophic factor (MANF) and cerebral dopamine neurotrophic factor (CDNF) promote the survival of midbrain dopamine neurons in animal models of Parkinson’s disease (PD) little is known about endogenous concentrations of MANF and CDNF in human PD patients Our main objective was to study whether circulating concentrations of MANF and CDNF differ between PD patients and controls and if they correlate with clinical parameters Levels of circulating CDNF were studied for the first time Methods: MANF and CDNF levels were measured from serum samples of 34 PD patients and 35 controls using validated in-lab-designed enzyme-linked immunosorbent assay (ELISAs) MANF and CDNF mRNA levels in whole blood samples of 60 PD patients and 30 controls were measured by quantitative real time polymerase chain reaction (qRT-PCR) MANF concentrations in different blood cell types were measured by ELISA Results: Circulating MANF concentrations were significantly higher in PD patients compared to controls (P < 0.001) and were positively correlated with Beck Depression Inventory (BDI) depression rating MANF mRNA levels in the blood did not differ between PD patients and controls (P = 0.44) The mean concentration of serum CDNF was 33 pg/ml in the controls CDNF levels were not altered in PD patients (P = 0.25) Conclusion: MANF but not CDNF level was increased in the blood of PD patients It would be interesting to examine the blood level of MANF from early stage PD patients in future studies to test whether MANF can be used as a clinical marker of PD Since MANF and CDNF have protective properties for dopamine neurons they are potential therapeutic proteins for PD less is known about their association with human PD pathophysiology Here our aim was to study the possible association of circulating MANF and CDNF with human PD pathogenesis We measured serum MANF and CDNF concentrations from PD patients and controls and analyzed statistical correlations between their levels and known clinical parameters The mean age of the PD patients and healthy controls were 73.2 ± 8.0 and 73.0 ± 7.9 years The mean duration of PD was 7.1 ± 6.8 years and all subjects provided written informed consent Demographic and clinical data on the study populations included in ELISA or qRT-PCR analysis The control group was formed from healthy volunteers without any current neurological condition and individuals who visited outpatient or inpatient clinics of the Department of Neurology and Neurosurgery of Tartu University Hospital without any current neurodegenerative disease but because of other neurological conditions Blood samples were collected to BD Vacutainer® tubes and allowed to clot at room temperature Serum was separated by centrifugation at 1300 × g for 10 min at room temperature (RT) and stored at −80°C until analysis The development and validation of human MANF ELISA for the measurement of MANF in serum has been described earlier (Galli et al., 2016) The dynamic range of MANF ELISA is 62.5–2000 pg/ml Human MANF ELISA does not recognize recombinant human CDNF serum samples were diluted at 1:20 in blocking buffer [1% casein in phosphate buffered saline To block interference caused by heterophilic antibodies (HAs) Immunoglobulin Inhibiting Reagent (IIR; BioIVT) was added to the serum samples at concentration of 500 mg/l Diluted samples and standards were applied to 96-well plates coated with goat anti-human MANF antibody (AF3748 and incubated overnight at +4°C in agitation bound MANF on the plates was detected using horseradish peroxidase (HRP)-conjugated mouse anti-human MANF antibody (4E12 Icosagen) and DuoSet ELISA Development System (R&D Systems) Absorbance was read at 450 nm and 540 nm using VICTOR3 plate reader The cELISA was run exactly as the CDNF ELISA; the only difference was a coating antibody opposed to goat anti-hCDNF used in the CDNF ELISA Cross-reactivity of cELISA for neither recombinant CDNF nor MANF was verified at a concentration of 2 ng/ml Linearity of dilution and recovery of spiked CDNF in serum was tested in the presence of IIR we pooled 10 subjects’ blood obtained from the Finnish Red Cross (license 43/2017) A total of 50 ml citrate-blood was centrifuged at 150 × g for 20 min at room temperature with no brake applied The platelet-rich plasma was transferred into a new tube without disturbing the buffy coat The sample was mixed gently to prevent platelet activation and centrifuged at 100 × g for 15–20 min at RT to pellet contaminating red and white blood cells (RBCs and WBCs) The remaining supernatant was centrifuged at 800 × g for 20 min at RT to pellet platelets Isolated platelets were rinsed twice with 1 mM EDTA in PBS (pH 7.4) and homogenized in 400 μl of lysis buffer (20 mM Tris–HCl Complete Mini protease inhibitor cocktail (Roche)) the sample was centrifuged at 12,000 × g for 20 min at + 4°C and the supernatant was stored at −80°C until analysis WBCs were collected by isolating the buffy coat of the initial centrifugation Contaminating RBCs were lysed by the addition of 0.5 ml of eBioscienceTM RBC Lysis Buffer (Invitrogen) and incubated for 15 min at RT WBCs were pelleted by centrifugation at 500 × g for 5 min at RT and the pellet was carefully resuspended in cold PBS and centrifuged again The washed pellet was homogenized in 400 μl of lysis buffer the top layer contaminated with buffy coats was removed and 400 μl of the RBC layer was collected 8 ml of PBS was added to the RBC layer and centrifuged at 500 × g for 10 min at RT and the washing was repeated two more times The pellet of RBCs was homogenized in 800 μl of lysis buffer Mesencephalic astrocyte-derived neurotrophic factor in the homogenates was quantitated by hMANF ELISA and the result normalized to the total protein concentration measured by DC Protein Assay (Bio-Rad Laboratories) Protein samples derived from fractionated blood cells were reduced by boiling with β-mercaptoethanol separated on 4–15% SDS-PAGE (MiniProtean® TGXTM Bio-Rad; 50 μg/lane) and blotted on a nitrocellulose membrane Proteins were stained with Ponceau S (0.1% in 5% acetic acid) after which MANF was detected with rabbit anti-MANF (1 μg/ml Icosagen) followed by HRP-conjugated secondary antibody against rabbit IgG and enhanced chemiluminescence (ECL) Western Blotting Substrate kit (Pierce) Whole blood samples were collected into Tempus Blood RNA tubes (Applied Biosystems) and frozen at −80°C Total RNA was isolated using Tempus Spin RNAS isolation kit (Applied Biosystems) 200 ng of RNA was used for cDNA synthesis using High Capacity cDNA Reverse Transcription Kit with RNase Inhibitor (Applied Biosystems) cDNA was used as a template for TaqMan® qRT-PCR analysis in the ABI Prism 7900HT Sequence Detection System (Applied Biosystems TaqMan® Gene Expression Master Mix and FAM labeled TaqMan (Applied Biosystems) gene assays were used to detect the mRNA expression level of the gene of interest and of actin as a reference gene The TaqMan probes used were: Hs00180640_m1 (MANF) Reactions were carried out in four replicates Data was analyzed using the 2(-Delta Delta C(T)) method where the gene expression levels were normalized to the level of the actin beta housekeeping gene The distributions of MANF and CDNF concentrations were skewed (Shapiro–Wilk test thus non-parametric statistical tests were carried out to analyze serum data Bivariate correlations were analyzed with Spearman’s correlation test and Mann–Whitney U-tests were used to compare MANF and CDNF serum levels in different groups qRT-PCR data was analyzed with the parametric unpaired t-test P ≤ 0.05 was considered statistically significant for all tests Statistical analyses were performed using Software Package for Social Science (SPSS) v All results are expressed as mean ± SD The average serum MANF concentration was twice as high in PD patients compared to their age-matched controls (Figure 1A) Serum MANF concentration was 10.2 ± 8.6 ng/ml (median: 6.7 ng/ml n = 34) in PD patients and 5.0 ± 4.0 ng/ml (median: 4.3 ng/ml n = 35) in the control group (P < 0.001) The difference in MANF serum concentration between the groups was 5.2 ng/ml (A) Increased levels of circulating MANF (Mann–Whitney U-test P < 0.001) in PD patients versus controls as measured by in-lab-designed ELISA (B) Positive correlation between MANF concentration and Beck Depression Inventory (BDI) score in PD patients (rs = 0.42; P = 0.02) (C) The average level of serum MANF was higher in PD patients scoring 18 or more BDI points than in patients with scores of 17 or less (Mann–Whitney U-test (D) MANF mRNA levels do not differ between the blood of PD patients and controls (t-test Correlations between serum MANF and clinical variables in PD patients Next, we used qRT-PCR analysis to measure MANF mRNA levels in whole blood derived from the PD patients and controls. However, MANF transcripts were not elevated in the blood of PD patients compared to controls (P = 0.44; Figure 1D) CDNF levels in serum were much lower than those of MANF The range of calculated serum CDNF concentrations in the study population was 4.3–134.4 pg/ml As the lower limit of detection (LLOD) of our hCDNF ELISA is 6.2 pg/ml and the sera need to be diluted 1:4 for optimal background control the minimal CDNF concentration that can reliably be distinguished from the blank is 24.8 pg/ml (A) Similar levels of serum CDNF in PD patients and controls as measured by in-lab-designed hCDNF ELISA (Mann–Whitney U-test LLOD; lower limit of detection when samples are diluted 1:4 (B) Positive correlation of MANF and CDNF levels in the sera of PD patients (rs = 0.41 (C) Increased levels of CDNF mRNA in the blood of PD patients compared to controls (t-test MANF and CDNF concentrations correlated positively in the sera from the PD patients (rs = 0.41, P = 0.016, n = 34, Figure 2B) but not in those from the controls (rs = 0.18 Using qRT-PCR we observed that CDNF gene expression was upregulated in whole blood samples of PD patients by 26% as compared to controls (P = 0.015; Figure 2C) Since MANF and CDNF promote the survival of brain dopamine neurons in animal models of PD (Lindholm et al., 2007; Voutilainen et al., 2009; Airavaara et al., 2012; Back et al., 2013; Ren et al., 2013; Garea-Rodriguez et al., 2016; Hao et al., 2017; Liu et al., 2018) we wanted to study whether their endogenous levels are altered in human subjects with PD which would indicate a possible contribution to the disease mechanism Serum was chosen for the study since its collection is minimally invasive and endogenous levels of circulating MANF and CDNF in human PD have not been addressed before the average MANF level was significantly higher in patients classified as depressed based on a BDI score of 18 or higher It is unclear whether the observed increase in MANF is directly related to depression or whether it reflects PD pathophysiology leading to depression it would be informative to analyze MANF levels in non-PD subjects diagnosed with depression and compare them to healthy subjects and those with PD we report for the first time that CDNF can be detected in the blood circulation The basal levels of CDNF in human circulation are clearly lower than the levels of MANF The difference between MANF and CDNF levels was approximately 170-fold (i.e. We found a positive correlation between MANF and CDNF levels in the sera of PD patients suggesting that patients having high MANF serum level also had higher CDNF levels This correlation was not observed in the control population implying that the release of MANF and CDNF to the blood circulation might be related to a pathological state the average levels of CDNF were not altered in subjects with PD It should be noted that in 19% (13/69) of the samples CDNF-readings remained under detection limit a more sensitive ELISA could give a different result to that we report here A recent study shows that CDNF levels were increased in the hippocampi of PD patient brain. Differently from CDNF, hippocampal levels of MANF were unaltered in PD (Virachit et al., 2019) Whether circulating and brain tissue levels of CDNF and MANF show any correlations in PD remains to be studied Indeed, the origins of MANF and CDNF in serum are still unknown. For example, brain-derived neurotrophic factor is stored in platelets and released upon stimulation (Fujimura et al., 2002) We found that MANF is present in high amounts in the platelets but whether they release MANF into the circulation is unclear We have not detected differences between average concentrations of MANF in human serum and plasma (unpublished observations) suggesting that clot-forming platelets are not the major source of serum MANF MANF mRNA levels in whole blood did not differ between PD patients and controls suggesting that the increased MANF in the serum of PD patients was not derived from blood cells while we observed increased CDNF mRNA levels in the blood of PD patients circulating levels of CDNF were not significantly changed in PD suggesting that CDNF mRNA levels in blood cells and the levels of circulating CDNF do not correlate Since increased serum MANF levels were also observed in PD patients it is possible that the molecular mechanisms regulating MANF concentrations are similar both in diabetes and in PD Detection of the PD pathogenesis before the onset of motor symptoms is an important step toward developing disease-modifying therapies Our results show that MANF serum concentration was doubled in patients with PD compared to age-matched controls In future studies it would be interesting to examine circulating MANF levels from early stage PD patients to test whether MANF can be used as a clinical marker of PD The datasets generated for this study are available on request to the corresponding author All authors revised and approved the final manuscript for submission This study was supported by the Academy of Finland (Grants 268662 and 310891) the Graduate School in Pharmaceutical Sciences and by the Grants PUT1239 and IUT2-4 of the Estonian Research Council PL and MS are inventors of the CDNF and MANF patents that are owned by Herantis Pharma Plc MS is also a shareholder of the Herantis Pharma Plc The remaining 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 and Martti Vaske are thanked for excellent technical assistance The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnins.2019.00929/full#supplementary-material CDNF protects the nigrostriatal dopamine system and promotes recovery after MPTP treatment in mice Gene therapy with AAV2-CDNF provides functional benefits in a rat model of Parkinson’s disease Google Scholar MANF regulates dopaminergic neuron development in larval zebrafish Clinical progression in Parkinson disease and the neurobiology of axons Review: sporadic Parkinson’ disease: development and distribution of alpha-synuclein pathology A practical method for grading the cognitive state of patients for the clinician Google Scholar Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation Increased circulating concentrations of mesencephalic astrocyte-derived neurotrophic factor in children with type 1 diabetes Garea-Rodriguez Comparative analysis of the effects of neurotrophic factors CDNF and GDNF in a nonhuman primate model of parkinson’s disease A comparison of clinical and pathological features of young- and old-onset Parkinson’s disease Movement disorder society-sponsored revision of the unified parkinson’s disease rating scale (MDS-UPDRS): scale presentation and clinimetric testing results Long-term protective effects of AAV9-mesencephalic astrocyte-derived neurotrophic factor gene transfer in parkinsonian rats Less than obvious - statistical treatment of data below the detection limit CrossRef Full Text | Google Scholar Google Scholar ‘Sniffin’ sticks’: olfactory performance assessed by the combined testing of odor identification odor discrimination and olfactory threshold CDNF protein therapy in parkinson’s disease Health-related quality of life in Parkinson’s disease: a cross-sectional study focusing on non-motor symptoms Unconventional neurotrophic factors CDNF and MANF: Structure physiological functions and therapeutic potential MANF is widely expressed in mammalian tissues and differently regulated after ischemic and epileptic insults in rodent brain Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo MANF improves the MPP(+)/MPTP-induced Parkinson’s disease via improvement of mitochondrial function and inhibition of oxidative stress Evidence that DmMANF is an invertebrate neurotrophic factor supporting dopaminergic neurons astrocyte-derived neurotrophic factor with selectivity for dopaminergic neurons AAV2-mediated striatum delivery of human CDNF prevents the deterioration of midbrain dopamine neurons in a 6-hydroxydopamine induced parkinsonian rat model Amantadine in the treatment of Parkinson’s disease Google Scholar Recognizing depression in patients with Parkinson’s disease: accuracy and specificity of two depression rating scale The accuracy of diagnosis of major depression in patients with Parkinson’s disease: a comparative study among the UPDRS the geriatric depression scale and the Beck depression inventory Levels of glial cell line-derived neurotrophic factor are decreased but fibroblast growth factor 2 and cerebral dopamine neurotrophic factor are increased in the hippocampus in parkinson’s disease doi: 10.1111/bpa.12730 [Epub ahead of print] Mesencephalic astrocyte-derived neurotrophic factor is neurorestorative in rat model of Parkinson’s disease Spatiotemporal expression of MANF in the developing rat brain Deficiency of IRE1 and PERK signal pathways in systemic lupus erythematosus Circulating mesencephalic astrocyte-derived neurotrophic factor is increased in newly diagnosed prediabetic and diabetic patients Taba P and Lindholm P (2019) Increased Serum Levels of Mesencephalic Astrocyte-Derived Neurotrophic Factor in Subjects With Parkinson’s Disease Copyright © 2019 Galli, Planken, Kadastik-Eerme, Saarma, Taba and Lindholm. 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: Päivi Lindholm, cGFpdmkucHVsa2tpbGFAaGVsc2lua2kuZmk= 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 Please press and hold the button until it turns completely green If you believe this is an error, please contact our support team 147.45.197.102 : 487b1b54-ff2b-4b65-a652-049eac68 (LONDON) -- At least two people were killed and several others were injured when a car drove into a crowd in Mannheim "A 40-year-old suspect drove a car into a group of people who were in the Planken area of Mannheim city center," the police statement said "Two people were killed and five seriously injured." A search of the area was immediately launched and a suspect was identified and arrested Police said that all bridges and main roads were initially blocked off and authorities asked the public to stay away from the city center police reopened the area after issuing an all-clear Video footage from Paradeplatz Square in the center of Mannheim showed shoppers standing outside an area cordoned off by police tape and strewn with debris First responders could be seen tending to at least one injured person local time in the Planken shopping district area near Paradeplatz Square is a German citizen from Rhineland-Palatinate The incident occurred as people were gathering in central Mannheim for an annual German carnival celebration Witness Manu Brioso told ABC News that he was taking a class in a building in the Paradeplatz area when he saw the car involved in the incident pass by on the street before it struck a crowd of people "The school told us what had happened and that we couldn't leave the school because police had cordoned off the area," Brioso said Security video obtained by ABC News showed the vehicle appeared to be speeding down a street before the incident drawing the attention of people seated at a sidewalk cafe and pedestrians some rushing across the street to get out of the car's path Officials at the Mannheim University Hospital said they received an emergency alert at 12:20 p.m local time about a possible mass casualty incident in downtown Mannheim and activated the hospital's emergency plan in preparation for treating the injured The hospital reported receiving many injured patients The hospital said its intensive care unit was full due to the arrival of a high number of critical patients eight trauma teams were treating both adults and children all of the hospital's entrances were closed to the public The deadly incident comes in the wake of two intentional car-ramming attacks in Germany and at a time of heightened security across the country a 24-year-old suspect drove a car into a crowd in Munich gathered for a trade union demonstration killing a 37-year-old mother and her 2-year-old daughter and injuring 37 people purportedly confessed to investigators that the act was deliberate said the suspect "gave an explanation I would summarize as religious motivation." a car-ramming attack occurred at a Christmas market in Magdeburg that left five people dead and around 200 injured Al-Abdulmohsen was charged with five counts of murder and multiple counts of both attempted murder and causing grievous bodily harm The Mannheim incident comes at the start of the Muslim holy month of Ramadan and amid a threat environment that has prompted Western officials to issue warnings to law enforcement and intelligence agencies in the United States and Western Europe National Counterterrorism Center last week an ISIS-aligned network released a poster called "Choose Your Next Target!" and lists four upcoming festivals and parades The poster features images of a bloody knife and pistol Officials noted that last year during Ramadan ISIS-Khorasan attacked Crocus City Hall in Moscow ISIS released a rare audio statement from its official spokesman -- which supporters subsequently translated into over a dozen languages including English -- celebrating that attack and calling for more violence against Christian and Jewish communities during Ramadan," officials said 14 people were killed and numerous others were injured in a car ramming attack on Bourbon Street in New Orleans' French Quarter The suspect was 42-year-old Army veteran Shamsud-Din Jabbar who was killed in a gunfight with police officers the New York Police Department and the Department of Homeland Security have issued notices alerting law enforcement to terrorism fears associated with Ramadan warned that "malicious actors from across the ideological spectrum may view Ramadan as an ideal time to commit attacks." The assessment reflects prior targeted acts of violence disrupted plots and recent violent extremist propaganda "The current dynamic threat environment necessitates elevated vigilance at mass gatherings especially during the Islamic holy month of Ramadan," the NYPD document said The DHS document noted that messaging from foreign terrorist organizations calling for violence during Ramadan "adds to a heightened concern of homegrown violent extremist attacks following the 2025 New Year’s ISIS-inspired attack in New Orleans likely raising the potential for violence from HVEs [homegrown violent extremists] during this year’s observance." Joe Simonetti and Zoe Magee contributed to this report Dana is a reporter and Travel Tomorrow’s Associate Editor She graduated in Political Science and International Relations She moved to Brussels from Romania for her studies and Mont des Arts made her fall in love with the city and remain here Plans to redevelop around 300,000 m² of office space in the heart of Brussels have been announced entrusted to Plusoffice Architects and Cityforward aims to transform the city’s European Quarter into a sustainable city district and green neighbourhood The European Commission is selling back 21 buildings to the city of Brussels in an attempt to reduce the institution’s carbon emissions Aligned with the objectives of the European Green Deal of reducing emissions by 55% by 2030 the Commission is counting on hybrid and remote working to scrap the high carbon footprint office buildings from its green balance sheet We’re delighted to enter a new phase of what will become a pioneering project transforming the European district in Brussels into a sustainable Cityforward is a property fund established by the Belgian Federal Holding and Investment Company and insurance company Ethias Their plan it to transform the 300,000 m² of office space into sustainable buildings Plusoffice Architects will be the design team of the project consisting of accomplished architects and experts that will spend the coming months working on feasibility studies urban planning integration and stakeholder consultations Their efforts will be supported by RE-ST and Osmos Network two expert firms in sustainable urban development “This design team shares our global vision to transform the heart of Europe into a vibrant urban district The input and involvement of all stakeholders are an essential part of the whole project And this design team really wants to use it for synergy” The design team is now drawing up the framework where they define the ideal mix of offices green and open spaces and different types of homes they consider the maximum desired building volume where space can be freed up by changing boundaries and how projects best fit within the surrounding neighbourhood “The ambitious team around Plusoffice Architects has clearly shown how it wants to find common ground between private and public interests with a healthy critical attitude” “This is essential in an urban project such as this They want to initially gain trust by engaging constructively with the different stakeholders The collaboration with RE-ST and Osmos brings additional expertise to the table and ensures there is sufficient manpower to get everything done during peak periods.” the design team will also explicitly focus on various aspects of sustainability This includes reducing energy consumption in the offices improving mobility in the district and creating new green spaces Cityforward wants this approach to have a positive impact on the environment as well as contribute to the well-being and quality of life of those who live Essential cookies enable basic functions and are necessary for the proper function of the website Statistics cookies collect information anonymously This information helps us to understand how our visitors use our website I recently had the pleasure of interviewing a man who has over the years received the applause of his audience with grace and humility – even as the applause and ovations get louder and longer Armenian-born Charles Aznavour is an icon in the world of music tired.  He left Avignon that day by Thalys to Antwerp together with his entourage and his daughter Katia Aznavour (from his third marriage with Ulla Thorsell) Evi Van der Planken: You started to perform at a very young age – you were 9 years old.  What was that like Les émigrants.  “When you start living in a country that’s not yours you have to learn everything:  the language the habits… An immigrant isn’t always accepted with open arms 1924 while his parents were waiting for a visa to enter the United States with hopes of a better future.  Due to the birth of Shahnour Varenagh Aznavourian the family was left stranded in Paris.  His parents chose to start a small restaurant in Paris although the recession of 1929 soon ended this project.  After that Aznavour says.  He sang in cabarets and clubs in Pigalle and Mont-Parnesse this wasn’t enough to make him give up; together with Pierre Roche he formed a duo Evi Van der Planken: These days you are still performing.  It is simply astonishing the length and scope of your marvelous career The success didn't come overnight; he had to work very hard for it. Meanwhile Aznavour met Piaf when he was still performing with Pierre Roche.  She encouraged him to write his own chansons.  Thanks to Piaf he had the opportunity to perform in Montreal Charles Aznavour: I spent several years in the entourage of Edith Piaf – she is the one who taught me to stay true to my own self when performing He went on to say: "The image that several authors and cineastes have of Edith Piaf doesn’t serve her right I still picture her walking on a bridge in Lausanne with a green balloon on a string in her hand  Edith and I were accomplices in laughter."                         Evi Van der Planken: Let’s look at your impressive curriculum: you wrote more than a thousand songs and musicals You are ambassador to Armenia.  What event had the biggest impact on you and why very humbly: “It was not events that marked my life and career; it was more the people I met.” Evi Van der Planken: I decided to ask him He responds very decisive and to the point: Photography and Cuisine He is not about to deliver a thesis about art; rather he brings up the forms of art where he will always find it c'est une photo" – “writing a chanson is as if I put my life into a photo.” Some songs are like a polaroid: one by one appear the figures Evi Van der Planken: If you would have to choose one artist over all other art-forms a spectacle. Trennet was a man of great ideas; in all the years we knew each other he never told the same joke twice.  He surprised his entourage always with his fresh mind always innovating.  That was his greatest gift Evi Van der Planken: You wrote in total over 2000 songs Charles Aznavour: I didn’t write or compose that many songs about love. I wrote songs about all facets of life. But people mostly remember my love songs Charles Aznavour: Love is not an art principal this was not the answer I expected from Aznavour I expected him to place love on the top of his list sitting next to him once the interview was over gave me the feeling that nostalgia has become more precious Image above: Charles Aznavour (b 1924) – French singer © Mariusz Kubik ArtDependence Magazine is an international magazine covering all spheres of contemporary art ArtDependence features the latest art news highlighting interviews with today’s most influential artists fair directors and individuals at the axis of the arts The magazine also covers series of articles and reviews on critical art events new publications and other foremost happenings in the art world If you would like to submit events or editorial content to ArtDependence Magazine, please feel free to reach the magazine via the contact page. 2023 Photo: Martijn Planken via LinkedInBrewing giant Heineken has scrapped a new poster campaign from the Dutch streets because the models look too young Heineken decided to take away the posters for its low alcohol “softer” beer Silver after a complaint from responsible drinking campaign group Stiva Stiva was tipped off by a LinkedIn comment from campaigner Martijn Planken “I just asked three teenagers how old these people are All three said between 16 and 18,” Planken said The models’ hair and clothing also made them out to be “youngsters promoting a new beer,” Planken said The code states that models in alcohol advertising must be at least 25 head of the responsible drinking campaign group Stiva who raised the issue with the brewing group We could not provide the Dutch News service without the generous support of our readers Your donations allow us to report on issues you tell us matter and provide you with a summary of the most important Dutch news each day Many thanks to everyone who has donated to DutchNews.nl in recent days We could not provide this service without you Please help us making DutchNews.nl a better read by taking part in a short survey Larry DeSmedt (aka Indian Larry) (1949-2004) grew up in the Newburgh Larry's first build was when he took his little sister Tina's tricycle and equipped it with Schwinn bicycle handlebars and a lawn mower engine Larry was friends with Motorcyclepedia Museum founder Ted Doering Jerry's influence on Larry would be evidenced later in life in by his ride selection and his love for this sport had a profound effect on Larry "Larry always spoke about motorcycles as visceral objects," Ted said "noting once that he would like a 'clear,' see-through transmission case to view the gears working He would fabricate or customize every piece because on a motorcycle visited the museum for the first time and were so impressed with the Indian collection that they decided they needed to raise awareness of this special collection A special event to celebrate Indian Larry was envisioned Selecting a date was easy: Make it close to the Indian Larry Legacy block party that is held in Brooklyn Among the fans that gather to celebrate Larry's life is a special group from Norway These unique members of the IL tribute club had never met Larry but found his life story that was known internationally to be worthy of tribute Larry's family met members of this fan club and instantly formed a special bond The museum tribute date had to be held when the Norwegians could be in town Larry's family and friends will gather at the Motorcyclepedia Museum in Newburgh Many special guests will be in attendance: Larry's sister Bambi the Mermaid; co-workers Bobby and Elisa Seeger of Indian Larry Motorcycles; the field portrait mower Gary Planken; as well as members of IL Tribute Norway new items from the family collection will be added to the Indian Larry exhibit Items including the motor head urn created by IL Legacy shop Iron Horse magazines and treasured family photos will be on indefinite loan to the museum Indian Larry Motorcycles will be present and will display several original Indian Larry motorcycles Tina DeSmedt-Wells contributed to this story US EditionUK EditionScottish SunIrish SunSearchMy Account It takes a special kind of genius to guide a team with the level of talent that France have and Didier Deschamps is the man who fits the bill The 54-year-old enjoyed the sort of playing career that many could only dream of with the likes of Marseille not to mention winning 103 caps for Les Bleus It was there that he won the World Cup in 1998 and the European Championships in 2000 giving him the perfect experience to lead their current star-studded squad He also won the 2018 World Cup as a manager and can win back-to-back titles as they face Argentina in Sunday's final Ousmane Dembele and Olivier Giroud in his ranks it will take a big personality to keep those egos in check In a profile of Deschamps in The Times, the head coach's superstitions are laid bare with the France boss watching 12 matches every weekend. It also takes a special kind of focus and strength, mentally and physically, to be at the top level like he is right now. Deschamps holds a plank for one hour every day while doing other activities like listening to music. Deschamps told RMC Sport: “I do daily plank support for hours every day. I'm even a little sick in this aspect. because There are too many people in my mind and now I am used to this kind of practice My wife always tells others: 'When he (Deschamps) does certain things he is always a bit extreme.' But this way of mine has exercised both my body and mind I couldn't complete the exercises I did now I had requirements for other aspects of my body "Now these trainings are more of a challenge and enjoyment I would definitely not do it like this." Deschamps also has other bizarre routines like shaving the head of his assistant Given France's stunning record in major competitions, it's clearly a superstition that is paying dividends, with France one match away from back-to-back World Cup titles. He would be just the second international manager to win the competition twice If they manage to pull it off against Argentina then there's no doubt that Deschamps will get the plaudits that he undoubtedly deserves talkSPORT is bringing you wall-to-wall coverage of the 2022 World Cup We are broadcasting all 64 games in the tournament live with over 600 hours of coverage across our network You can tune in to talkSPORT and talkSPORT 2 via our free online streaming service at talkSPORT.com talkSPORT is widely available across the UK via DAB digital radio and on 1089 or 1053 AM Six universities and colleges, including the UvA, are participating in the Dry January campaign IkPas. Of those six universities and colleges – 205,000 students – only 23 students signed up. Did students become too fond of alcohol during the corona crisis? There were plans to set up a large-scale campaign on the UvA campus, among other things, but corona caused problems, says IkPas campaign manager Martijn Planken. ‘The lockdown resulted in empty UvA buildings, so there was little point in putting up posters everywhere. Online opportunities were also limited, because not everyone reads the newsletter. So the question was whether the message would get across.’ The message does not seem to have really gotten through, but that was in line with expectations, according to Planken. ‘We want to make it a tradition, so you have to start somewhere. We didn’t think we’d start with thousands of students right away, but we wanted to give them a taste of the concept, so that we’re really well prepared next year.’ Duncan does drink ‘exponentially less’ than before the corona crisis. He used to be in the pub three to four nights a week and sometimes drank ten glasses of alcohol in a day several times a week. ’More and more I’m wondering why I am really doing it. If I’m with friends and we’re not going to get waisted, why should I drink three or four beers?’ He didn’t find his pre-crisis drinking problematic. ‘I’m not an alcoholic, I don’t drink on my own. I think a cup of tea is better.’ He also doesn’t necessarily see many problematic cases around him. There are people for whom it has been a problem for a long time, but that is a very small minority. I rather see a cocaine problem around me.’ Wini drinks about five days a week. ‘Usually that’s three glasses a night, although before Dry January it was more. I also started drinking more during corona, because there’s not much to do and the easiest thing to do is having a night of social drinking.’ She doesn’t have any worries about her drinking. ‘Maybe it’s a lot for the average person, but not for the average student. Around me I also don’t see that many people suffer from their alcohol consumption. According to the UvA, there are many students who do, then it’s good that they are trying to do something about it. But for myself, it’s not a problem. I still function, even when I sleep less.’ Chemistry student and leader of student beer party Slaafs Daan Jellema (23) thinks an alcohol policy at the university is nonsense anyway. ‘I’d rather not drink for a month than participating in a campaign like that. Although the UvA is still doing relatively okay. In Utrecht, beer is no longer allowed on campus. Here, at least, they understand that it’s part of student life.’ Daan spends the scholarship he receives for his student council membership on free beer for his party. ‘Beer is sociable, fun, it connects people.’ But it's not like he drinks extremely. ‘I don’t always have to have beer or be tipsy. Sometimes I drink three times a week, sometimes not for a few weeks. I’m better at giving away beer than I am at drinking beer.’  In any case, the university shouldn’t get involved, he says. ’I think alcohol policy is a bit childish. We are adults, we just have our own responsibility.’ ​CategoriesCategoriesEnglishGENERAL, ECONOMY, EUBelgium buys 23 EU buildings to transform Brussels' European quarter29 April 2024 The Belgian government is buying 23 office buildings from the European Commission The deal should lead to a major transformation of the European quarter in Brussels the European Commission is selling a portfolio of 23 buildings to the Federal Holding and Investment Company (SFPIM) of the Belgian government The government’s investment company has in turn given the 21 buildings on a long lease to the Belgian fund Cityforward set up by SFPIM and insurer Ethias and managed by Brussels-Antwerp partner Whitewood with a total area of 300,000 square metres will be transformed into sustainable offices (70 per cent) flats (25 per cent) and shops or public facilities (5 per cent) There will be about 750 to 800 new flats in the district and the first new residents and office workers should move in from 2028 The total cost of the changes to the buildings is estimated to be of the same order of magnitude as that of the purchase bringing the total investment to almost 2 billion euros The investment should lead to a profound transformation of the neighbourhood “The foundations have been laid to become in the near future the epitome of a diversified urban environment with sustainable workplaces in a neighbourhood where it is good to live,” said Frédéric Van der Planken CEO of Whitewood and manager of Cityforward have been sold to the Vicinity Affordable Housing Fund and neighbourhood developer Matexi They will redevelop them into sustainable and affordable rental and owner-occupied flats The European quarter in Brussels © BELGA PHOTO THIERRY ROGE Copy linkGet updates in your mailboxYour email addressSubscribeBy clicking "Subscribe" I confirm I have read and agree to the Privacy Policy rapid and high-quality information 24 hours a day from Belgium and abroad to all Belgian media not to mention entertainment and lifestyle our journalists and press photographers produce hundreds of photos and news stories Since the end of March 2022 English has been added as a language businesses and various organisations that need reliable information Belga News Agency also offers a comprehensive range of corporate services to meet all their communication needs www.belganewsagency.eu Home > Financial Planning > Finalists for Women in Wealth Awards 2024 announced The finalists for the inaugural Women in Wealth Awards 2024 with a monumental 138 finalists sent through to the next round The Women in Wealth Awards recognise and reward women who have shown commitment to the financial services industry through leadership innovation and advocacy in the fields they are passionate about The awards acknowledge those women who have embodied the generational change and professionalism that the industry continues to reflect The awards celebrate women across the various sectors that make up the wider financial services and wealth management industry There are also several advocacy and overall awards to recognise the women making contributions to others and their communities Ticket sales are live for those looking to purchase individual seats, standard tables of 10 or premium tables of 10 to support the finalists and celebrate the winners. Life/Risk Insurance Professional of the Year Marketing/ Communications Professional of the Year 20 years of morons in Canberra and look at the results How many academics actually understand the real world Money is leaving at a slower rate with this being considered by AMP management as a positive "Our recently launched digital advice solution for AMP Super members is providing simple intuitive retirement advice at no extra cost.”… A time when dozens of submissions were made 90 odd submissions ranging from clients be sent… I am curious how an industry super fund paraplanner whose scope of strategies and work would be severely curtailed by necessity to a small circle of super/pension/contribution and vaguely possibly death benefit strategies could WIN the award versus independent paraplanners whose scope and breadth of work and expertise would vastly outreach hers?????? Love to have transparency on judging criteria and how these all were assessed!!!