Caffeine as a tool for investigating the integration of Cdc25 phosphorylation, activity and ubiquitin-dependent degradation in Schizosaccharomyces pombe

The evolutionarily conserved Cdc25 phosphatase is an essential protein that removes inhibitory phosphorylation moieties on the mitotic regulator Cdc2. Together with the Wee1 kinase, a negative regulator of Cdc2 activity, Cdc25 is thus a central regulator of cell cycle progression in Schizosaccharomyces pombe. The expression and activity of Cdc25 is dependent on the activity of the Target of Rapamycin Complex 1 (TORC1). TORC1 inhibition leads to the activation of Cdc25 and repression of Wee1, leading to advanced entry into mitosis. Withdrawal of nitrogen leads to rapid Cdc25 degradation via the ubiquitin- dependent degradation pathway by the Pub1 E3- ligase. Caffeine is believed to mediate the override of DNA damage checkpoint signalling, by inhibiting the activity of the ataxia telangiectasia mutated (ATM)/Rad3 homologues. This model remains controversial, as TORC1 appears to be the preferred target of caffeine in vivo. Recent studies suggest that caffeine induces DNA damage checkpoint override by inducing the nuclear accumulation of Cdc25 in S. pombe. Caffeine may thus modulate Cdc25 activity and stability via inhibition of TORC1. A clearer understanding of the mechanisms by which caffeine stabilises Cdc25, may provide novel insights into how TORC1 and DNA damage signalling is integrated

Neuron-glial Interactions

Although lagging behind classical computational neuroscience, theoretical and computational approaches are beginning to emerge to characterize different aspects of neuron-glial interactions. This chapter aims to provide essential knowledge on neuron-glial interactions in the mammalian brain, leveraging on computational studies that focus on structure (anatomy) and function (physiology) of such interactions in the healthy brain. Although our understanding of the need of neuron-glial interactions in the brain is still at its infancy, being mostly based on predictions that await for experimental validation, simple general modeling arguments borrowed from control theory are introduced to support the importance of including such interactions in traditional neuron-based modeling paradigms.Junior Leader Fellowship Program by “la Caixa” Banking Foundation (LCF/BQ/LI18/11630006

Start-up rheometry of highly polydisperse magnetorheological fluids: experiments and simulations

An extensive experimental and simulation study is carried out in conventional magnetorheological fluids formulated by dispersion of mixtures of carbonyl iron particles having different sizes in Newtonian carriers. Apparent yield stress data are reported for a wide range of polydispersity indexes (PDI) from PDI = 1.63 to PDI = 3.31, which for a log-normal distribution corresponds to the standard deviation ranging from to . These results demonstrate that the effect of polydispersity is negligible in this range in spite of exhibiting very different microstructures. Experimental data in the magnetic saturation regime are in quantitative good agreement with particle-level simulations under the assumption of dipolar magnetostatic forces. The insensitivity of the yield stresses to the polydispersity can be understood from the interplay between the particle cluster size distribution and the packing density of particles inside the clusters

Free-Living Turtles Are a Reservoir for Salmonella but Not for Campylobacter

Different studies have reported the prevalence of Salmonella in turtles and its role in reptile-associated salmonellosis in humans, but there is a lack of scientific literature related with the epidemiology of Campylobacter in turtles. The aim of this study was to evaluate the prevalence of Campylobacter and Salmonella in free-living native (Emys orbicularis, n=83) and exotic (Trachemys scripta elegans, n=117) turtles from 11 natural ponds in Eastern Spain. In addition, different types of samples (cloacal swabs, intestinal content and water from Turtle containers) were compared. Regardless of the turtle species, natural ponds where individuals were captured and the type of sample taken, Campylobacter was not detected. Salmonella was isolated in similar proportions in native (8.0±3.1%) and exotic (15.0±3.3%) turtles (p=0.189). The prevalence of Salmonella positive turtles was associated with the natural ponds where animals were captured. Captured turtles from 8 of the 11 natural ponds were positive, ranged between 3.0±3.1% and 60.0±11.0%. Serotyping revealed 8 different serovars among four Salmonella enterica subspecies: S. enterica subsp. enterica (n = 21), S. enterica subsp. salamae (n = 2), S. enterica subsp. diarizonae (n = 3), and S. enterica subsp. houtenae (n = 1). Two serovars were predominant: S. Thompson (n=16) and S. typhimurium (n=3). In addition, there was an effect of sample type on Salmonella detection. The highest isolation of Salmonella was obtained from intestinal content samples (12.0±3.0%), while lower percentages were found for water from the containers and cloacal swabs (8.0±2.5% and 3.0±1.5%, respectively). Our results imply that free-living turtles are a risk factor for Salmonella transmission, but do not seem to be a reservoir for Campylobacter. We therefore rule out turtles as a risk factor for human campylobacteriosis. Nevertheless, further studies should be undertaken in other countries to confirm these results.This work was supported by the Conselleria de Infraestructura, Territorio y Medio Ambiente for their assistance and financial support (Life09-Trachemys, Resolution 28/02/12 CITMA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Marín, C.; Ingresa-Capaccioni, S.; González Bodí, S.; Marco Jiménez, F.; Vega Garcia, S. (2013). Free-Living Turtles Are a Reservoir for Salmonella but Not for Campylobacter. PLoS ONE. 8(8):1-6. https://doi.org/10.1371/journal.pone.0072350S1688(2012). The European Union Summary Report on Trends and Sources of Zoonoses, Zoonotic Agents and Food‐borne Outbreaks in 2010. EFSA Journal, 10(3). doi:10.2903/j.efsa.2012.2597Kapperud, G. (2003). Factors Associated with Increased and Decreased Risk of Campylobacter Infection: A Prospective Case-Control Study in Norway. American Journal of Epidemiology, 158(3), 234-242. doi:10.1093/aje/kwg139Mermin, J., Hutwagner, L., Vugia, D., Shallow, S., Daily, P., … Bender, J. (2004). Reptiles, Amphibians, and HumanSalmonellaInfection: A Population‐Based, Case‐Control Study. Clinical Infectious Diseases, 38(s3), S253-S261. doi:10.1086/381594De Jong, B., Andersson, Y., & Ekdahl, K. (2005). Effect of Regulation and Education on Reptile-associated Salmonellosis. Emerging Infectious Diseases, 11(3), 398-403. doi:10.3201/eid1103.040694NAKADAI, A., KUROKI, T., KATO, Y., SUZUKI, R., YAMAI, S., YAGINUMA, C., … HAYASHIDANI, H. (2005). Prevalence of Salmonella spp. in Pet Reptiles in Japan. Journal of Veterinary Medical Science, 67(1), 97-101. doi:10.1292/jvms.67.97Lafuente, S., Bellido, J. B., Moraga, F. A., Herrera, S., Yagüe, A., Montalvo, T., … Caylà, J. A. (2013). Salmonella paratyphi B and Salmonella litchfield outbreaks associated with pet turtle exposure in Spain. Enfermedades Infecciosas y Microbiología Clínica, 31(1), 32-35. doi:10.1016/j.eimc.2012.05.013Van PELT, W., de WIT, M. A. S., WANNET, W. J. B., LIGTVOET, E. J. J., WIDDOWSON, M. A., & van DUYNHOVEN, Y. T. H. P. (2003). Laboratory surveillance of bacterial gastroenteric pathogens in The Netherlands, 1991–2001. Epidemiology and Infection, 130(3), 431-441. doi:10.1017/s0950268803008392Havelaar, A. H., Haagsma, J. A., Mangen, M.-J. J., Kemmeren, J. M., Verhoef, L. P. B., Vijgen, S. M. C., … van Pelt, W. (2012). Disease burden of foodborne pathogens in the Netherlands, 2009. International Journal of Food Microbiology, 156(3), 231-238. doi:10.1016/j.ijfoodmicro.2012.03.029DOORDUYN, Y., VAN PELT, W., SIEZEN, C. L. E., VAN DER HORST, F., VAN DUYNHOVEN, Y. T. H. P., HOEBEE, B., & JANSSEN, R. (2007). Novel insight in the association between salmonellosis or campylobacteriosis and chronic illness, and the role of host genetics in susceptibility to these diseases. Epidemiology and Infection, 136(9), 1225-1234. doi:10.1017/s095026880700996xHAAGSMA, J. A., SIERSEMA, P. D., DE WIT, N. J., & HAVELAAR, A. H. (2010). Disease burden of post-infectious irritable bowel syndrome in The Netherlands. Epidemiology and Infection, 138(11), 1650-1656. doi:10.1017/s0950268810000531Allos, B. M., & Blaser, M. J. (1995). Campylobacter jejuni and the Expanding Spectrum of Related Infections. Clinical Infectious Diseases, 20(5), 1092-1101. doi:10.1093/clinids/20.5.1092Friedman, C. R., Hoekstra, R. M., Samuel, M., Marcus, R., Bender, J., … Shiferaw, B. (2004). Risk Factors for SporadicCampylobacterInfection in the United States: A Case‐Control Study in FoodNet Sites. Clinical Infectious Diseases, 38(s3), S285-S296. doi:10.1086/381598STUDAHL, A., & ANDERSSON, Y. (2000). Risk factors for indigenous campylobacter infection: a Swedish case-control study. Epidemiology and Infection, 125(2), 269-275. doi:10.1017/s0950268899004562NEIMANN, J., ENGBERG, J., MØLBAK, K., & WEGENER, H. C. (2003). A case–control study of risk factors for sporadic campylobacter infections in Denmark. Epidemiology and Infection, 130(3), 353-366. doi:10.1017/s0950268803008355DOORDUYN, Y., VAN DEN BRANDHOF, W. E., VAN DUYNHOVEN, Y. T. H. P., BREUKINK, B. J., WAGENAAR, J. A., & VAN PELT, W. (2010). Risk factors for indigenous Campylobacter jejuni and Campylobacter coli infections in The Netherlands: a case-control study. Epidemiology and Infection, 138(10), 1391-1404. doi:10.1017/s095026881000052xSchroter, M., Roggentin, P., Hofmann, J., Speicher, A., Laufs, R., & Mack, D. (2004). Pet Snakes as a Reservoir for Salmonella enterica subsp. diarizonae (Serogroup IIIb): a Prospective Study. Applied and Environmental Microbiology, 70(1), 613-615. doi:10.1128/aem.70.1.613-615.2004Van Meervenne, E., Botteldoorn, N., Lokietek, S., Vatlet, M., Cupa, A., Naranjo, M., … Bertrand, S. (2009). Turtle-associated Salmonella septicaemia and meningitis in a 2-month-old baby. Journal of Medical Microbiology, 58(10), 1379-1381. doi:10.1099/jmm.0.012146-0Williams, L. P. (1965). Pet Turtles as a Cause of Human Salmonellosis. JAMA: The Journal of the American Medical Association, 192(5), 347. doi:10.1001/jama.1965.03080180005001Feeley, J. C., & Treger, M. D. (1969). Penetration of Turtle Eggs by Salmonella braenderup. Public Health Reports (1896-1970), 84(2), 156. doi:10.2307/4593527Mermin, J., Hoar, B., & Angulo, F. J. (1997). Iguanas and Salmonella Marina Infection in Children: A Reflection of the Increasing Incidence of Reptile-associated Salmonellosis in the United States. PEDIATRICS, 99(3), 399-402. doi:10.1542/peds.99.3.399Rodgers, G. L., Long, S. S., Smergel, E., & Dampier, C. (2002). Salmonella Infection Associated With a Pet Lizard in Siblings With Sickle Cell Anemia: An Avoidable Risk. Journal of Pediatric Hematology/Oncology, 24(1), 75-76. doi:10.1097/00043426-200201000-00020Tu, Z.-C., Zeitlin, G., Gagner, J.-P., Keo, T., Hanna, B. A., & Blaser, M. J. (2004). Campylobacter fetus of Reptile Origin as a Human Pathogen. Journal of Clinical Microbiology, 42(9), 4405-4407. doi:10.1128/jcm.42.9.4405-4407.2004Hidalgo-Vila, J., Díaz-Paniagua, C., Pérez-Santigosa, N., de Frutos-Escobar, C., & Herrero-Herrero, A. (2008). Salmonella in free-living exotic and native turtles and in pet exotic turtles from SW Spain. Research in Veterinary Science, 85(3), 449-452. doi:10.1016/j.rvsc.2008.01.011Harris, J. R., Neil, K. P., Behravesh, C. B., Sotir, M. J., & Angulo, F. J. (2010). Recent Multistate Outbreaks of HumanSalmonellaInfections Acquired from Turtles: A Continuing Public Health Challenge. Clinical Infectious Diseases, 50(4), 554-559. doi:10.1086/649932Geue, L., & Löschner, U. (2002). Salmonella enterica in reptiles of German and Austrian origin. Veterinary Microbiology, 84(1-2), 79-91. doi:10.1016/s0378-1135(01)00437-0Sánchez-Jiménez, M. M., Rincón-Ruiz, P. A., Duque, S., Giraldo, M. A., Ramírez-Monroy, D. M., Jaramillo, G., & Cardona-Castro, N. (2011). Salmonella enterica in semi-aquatic turtles in Colombia. The Journal of Infection in Developing Countries, 5(05), 361-364. doi:10.3855/jidc.1126HEALTH SURVEY OF WILD AND CAPTIVE BOG TURTLES (CLEMMYS MUHLENBERGII) IN NORTH CAROLINA AND VIRGINIA. (2002). Journal of Zoo and Wildlife Medicine, 33(4), 311-316. doi:10.1638/1042-7260(2002)033[0311:hsowac]2.0.co;2Richards, J. M., Brown, J. D., Kelly, T. R., Fountain, A. L., & Sleeman, J. M. (2004). ABSENCE OF DETECTABLE SALMONELLA CLOACAL SHEDDING IN FREE-LIVING REPTILES ON ADMISSION TO THE WILDLIFE CENTER OF VIRGINIA. Journal of Zoo and Wildlife Medicine, 35(4), 562-563. doi:10.1638/03-070Hidalgo-Vila, J., Díaz-Paniagua, C., de Frutos-Escobar, C., Jiménez-Martínez, C., & Pérez-Santigosa, N. (2007). Salmonella in free living terrestrial and aquatic turtles. Veterinary Microbiology, 119(2-4), 311-315. doi:10.1016/j.vetmic.2006.08.012Acheson, D., & Allos, B. M. (2001). Campylobacter jejuni Infections: Update on Emerging Issues and Trends. Clinical Infectious Diseases, 32(8), 1201-1206. doi:10.1086/319760Briones, V., Tellez, S., Goyache, J., Ballesteros, C., del Pilar Lanzarot, M., Dominguez, L., & Fernandez-Garayzabal, J. F. (2004). Salmonella diversity associated with wild reptiles and amphibians in Spain. Environmental Microbiology, 6(8), 868-871. doi:10.1111/j.1462-2920.2004.00631.xMan, S. M. (2011). The clinical importance of emerging Campylobacter species. Nature Reviews Gastroenterology & Hepatology, 8(12), 669-685. doi:10.1038/nrgastro.2011.191Ugarte-Ruiz, M., Gómez-Barrero, S., Porrero, M. C., Álvarez, J., García, M., Comerón, M. C., … Domínguez, L. (2012). Evaluation of four protocols for the detection and isolation of thermophilic Campylobacter from different matrices. Journal of Applied Microbiology, 113(1), 200-208. doi:10.1111/j.1365-2672.2012.05323.xJeffrey, J. S., Tonooka, K. H., & Lozanot, J. (2001). Prevalence of Campylobacter spp. from Skin, Crop, and Intestine of Commercial Broiler Chicken Carcasses at Processing. Poultry Science, 80(9), 1390-1392. doi:10.1093/ps/80.9.1390Perko-Mäkelä, P., Isohanni, P., Katzav, M., Lund, M., Hänninen, M.-L., & Lyhs, U. (2009). A longitudinal study of Campylobacter distribution in a turkey production chain. Acta Veterinaria Scandinavica, 51(1). doi:10.1186/1751-0147-51-18Saelinger, C. A., Lewbart, G. A., Christian, L. S., & Lemons, C. L. (2006). Prevalence ofSalmonellaspp in cloacal, fecal, and gastrointestinal mucosal samples from wild North American turtles. Journal of the American Veterinary Medical Association, 229(2), 266-268. doi:10.2460/javma.229.2.266Chambers, D. L., & Hulse, A. C. (2006). Salmonella Serovars in the Herpetofauna of Indiana County, Pennsylvania. Applied and Environmental Microbiology, 72(5), 3771-3773. doi:10.1128/aem.72.5.3771-3773.2006Gaertner, J. P., Hahn, D., Jackson, J., Forstner, M. R. J., & Rose, F. L. (2008). Detection of Salmonellae in Captive and Free-Ranging Turtles Using Enrichment Culture and Polymerase Chain Reaction. Journal of Herpetology, 42(2), 223-231. doi:10.1670/07-1731.1Magnino, S., Colin, P., Dei-Cas, E., Madsen, M., McLauchlin, J., Nöckler, K., … Van Peteghem, C. (2009). Biological risks associated with consumption of reptile products. International Journal of Food Microbiology, 134(3), 163-175. doi:10.1016/j.ijfoodmicro.2009.07.001XIA, X., ZHAO, S., SMITH, A., MCEVOY, J., MENG, J., & BHAGWAT, A. (2009). Characterization of Salmonella isolates from retail foods based on serotyping, pulse field gel electrophoresis, antibiotic resistance and other phenotypic properties. International Journal of Food Microbiology, 129(1), 93-98. doi:10.1016/j.ijfoodmicro.2008.11.007Franco, A., Hendriksen, R. S., Lorenzetti, S., Onorati, R., Gentile, G., Dell’Omo, G., … Battisti, A. (2011). Characterization of Salmonella Occurring at High Prevalence in a Population of the Land Iguana Conolophus subcristatus in Galápagos Islands, Ecuador. PLoS ONE, 6(8), e23147. doi:10.1371/journal.pone.0023147Scheelings, T. F., Lightfoot, D., & Holz, P. (2011). PREVALENCE OF SALMONELLA IN AUSTRALIAN REPTILES. Journal of Wildlife Diseases, 47(1), 1-11. doi:10.7589/0090-3558-47.1.1Pasmans, F., Blahak, S., Martel, A., & Pantchev, N. (2008). Introducing reptiles into a captive collection: The role of the veterinarian. The Veterinary Journal, 175(1), 53-68. doi:10.1016/j.tvjl.2006.12.009Strohl, P., Tilly, B., Fremy, S., Brisabois, A., & Guerin-Faublee, V. (2004). Prevalence of Salmonella shedding in faeces by captive chelonians. Veterinary Record, 154(2), 56-58. doi:10.1136/vr.154.2.5

Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality

Background and purpose: Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions: During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Dynamical downscaling of historical climate over CORDEX Central America domain with a regionally coupled atmosphere–ocean model

The climate in Mexico and Central America is influenced by the Pacific and the Atlantic oceanic basins and atmospheric conditions over continental North and South America. These factors and important ocean–atmosphere coupled processes make the region’s climate a great challenge for global and regional climate modeling. We explore the benefits that coupled regional climate models may introduce in the representation of the regional climate with a set of coupled and uncoupled simulations forced by reanalysis and global model data. Uncoupled simulations tend to stay close to the large-scale patterns of the driving fields, particularly over the ocean, while over land they are modified by the regional atmospheric model physics and the improved orography representation. The regional coupled model adds to the reanalysis forcing the air–sea interaction, which is also better resolved than in the global model. Simulated fields are modified over the ocean, improving the representation of the key regional structures such as the Intertropical Convergence Zone and the Caribbean Low Level Jet. Higher resolution leads to improvements over land and in regions of intense air–sea interaction, e.g., off the coast of California. The coupled downscaling improves the representation of the Mid Summer Drought and the meridional rainfall distribution in southernmost Central America. Over the regions of humid climate, the coupling corrects the wet bias of the uncoupled runs and alleviates the dry bias of the driving model, yielding a rainfall seasonal cycle similar to that in the reanalysis-driven experiments.Universidad de Costa Rca/[805-B7-507]/UCR/Costa RicaCRYOPERU/[144-2015]//PerúUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI

Neuron-Glial Interactions

Although lagging behind classical computational neuroscience, theoretical and computational approaches are beginning to emerge to characterize different aspects of neuron-glial interactions. This chapter aims to provide essential knowledge on neuron-glial interactions in the mammalian brain, leveraging on computational studies that focus on structure (anatomy) and function (physiology) of such interactions in the healthy brain. Although our understanding of the need of neuron-glial interactions in the brain is still at its infancy, being mostly based on predictions that await for experimental validation, simple general modeling arguments borrowed from control theory are introduced to support the importance of including such interactions in traditional neuron-based modeling paradigms.Comment: 43 pages, 2 figures, 1 table. Accepted for publication in the "Encyclopedia of Computational Neuroscience," D. Jaeger and R. Jung eds., Springer-Verlag New York, 2020 (2nd edition