407 research outputs found
Non-Typhi Salmonella gastroenteritis in children presenting to the emergency department: characteristics of patients with associated bacteraemia
ABSTRACTThe records of children with Salmonella gastroenteritis only (n = 97), and those with associated bacteraemia (n = 64), seen in one medical centre during a 12-year period, were analysed retrospectively. Mean patient age was 2.24 ± 2.8 years (range, 0.05–16 years), and 49% were male. Children with bacteraemia presented after a longer duration of symptoms (7.0 ± 6.9 vs. 3.9 ± 4.6 days, p 0.0002), and had higher erythrocyte sedimentation rates (45 ± 22 vs. 33 ± 22 mm/h, p < 0.02) and lactate dehydrogenase values (924 ± 113 vs. 685 ± 165 IU/L, p 0.001). There was a trend in bacteraemic children towards immunosuppression (6.3% vs. 1.0%, p 0.08) and a lower number of siblings (2.9 ± 1.9 vs. 3.8 ± 2.7, p 0.063). Non-bacteraemic children had a more severe clinical appearance, and a higher percentage had a moderate to bad general appearance (51.5 vs. 29.7%, p < 0.01), with dehydration (37.1 vs. 18.8%, p 0.02) and vomiting (58.8 vs. 39.0%, p 0.02). Laboratory dehydration indicators were also markedly worse in non-bacteraemic children, with urine specific gravity of 1020 ± 9.4 vs. 1013 ± 9.0 (p 0.0002), base excess of −4.2 ± 3.0 vs. −2.5 ± 3.4 mEq/L (p 0.01), and blood urea nitrogen of 10.1 ± 7.0 vs. 7.4 ± 4.5 mg% (p 0.002). Thus, the clinical presentation of bacteraemic children was more gradual, and associated gastroenteritis and dehydration was less pronounced. These findings may contribute in part to the inadvertent discharge of bacteraemic children from the emergency department
Toward an Unsteady Aerodynamic ROM for Multiple Mach Regimes
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97065/1/AIAA2012-1708.pd
Linking compound weather extremes to Mediterranean cyclones, fronts, and airstreams
This is the final version. Available from Copernicus Publications via the DOI in this record. Data availability. ERA5 reanalysis is publicly available at
https://doi.org/10.24381/cds.adbb2d47 (Hersbach et al., 2023).
Mediterranean cyclone tracks are provided as a supplement of
Flaounas et al. (2023).Code availability. The code is not publicly accessible. The computations used for this work reduce to the simple frequency statistics
described in Sect. 2.4.Mediterranean cyclones are the primary driver of many types of surface weather extremes in the Mediterranean region, the association with extreme rainfall being the most established. The large-scale characteristics of a Mediterranean cyclone, the properties of the associated airflows and temperature fronts, the interaction with the Mediterranean Sea and with the topography around the basin, and the season of occurrence all contribute to determining its surface impacts. Here, we take these factors into account to interpret the statistical links between Mediterranean cyclones and compound extremes of two types, namely co-occurring rain-wind and wave-wind extremes. Compound extremes are attributed to a cyclone if they fall within a specially defined Mediterranean cyclone impact area. Our results show that the majority of Mediterranean rain-wind and wave-wind extremes occur in the neighbourhood of a Mediterranean cyclone, with local peaks exceeding 80 %. The fraction of compounds happening within a cyclone's impact area is highest when considering transition seasons and for rain-wind events compared with wave-wind events. Winter cyclones, matching with the peak occurrence of large and distinctively baroclinic cyclones, are associated with the highest compound frequency. A novel deconstruction of cyclones' impact areas based on the presence of objectively identified airstreams and fronts reveals a high incidence of both types of compound extremes below warm conveyor belt ascent regions and of wave-wind extremes below regions of dry intrusion outflow.Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungIsrael Science FoundationDe Botton Center for Marine Science at the Weizmann Institute of Scienc
Process-based classification of Mediterranean cyclones using potential vorticity
This is the final version. Available on open access from Copernicus Publications via the DOI in this recordCode availability:The code for the SOM classification algorithm is openly available at https://www.mathworks.com/help/deeplearning/gs/cluster-data-with-a-self-organizingmap.html (last access: 29 January 2024).Data availability: The composite cyclone tracks with the resulting cluster attribution are available in the supplementary assets of this paper. The track labels correspond to the composite cyclone track dataset at confidence level 5, made available as a Supplement by Flaounas et al. (2023) (“TRACKS_CL5.dat”).Mediterranean cyclones (MCs) govern extreme weather events across the Euro-African Basin, affecting the lives of hundreds of millions. Despite many studies addressing MCs in the last few decades, their correct simulation and prediction remain a significant challenge to the present day, which may be attributed to the large variability among MCs. Past classifications of MCs are primarily based on geographical and/or seasonal separations; however, here we focus on cyclone genesis and deepening mechanisms. A variety of processes combine to govern MC genesis and evolution, including adiabatic and diabatic processes, topographic influences, land-sea contrasts, and local temperature anomalies. As each process bears a distinct signature on the potential vorticity (PV) field, a PV approach is used to distinguish among different "types"of MCs. Here, a combined cyclone-tracking algorithm is used to detect 3190 Mediterranean cyclone tracks in ECMWF ERA5 from 1979-2020. Cyclone-centered, upper-level isentropic PV structures in the peak time of each cyclone track are classified using a self-organizing map (SOM). The SOM analysis reveals nine classes of Mediterranean cyclones, with distinct Rossby-wave-breaking patterns, discernible in corresponding PV structures. Although classified by upper-level PV structures, each class shows different contributions of lower-tropospheric PV and flow structures down to the surface. Unique cyclone life cycle characteristics, associated hazards (precipitation, winds, and temperature anomalies), and long-term trends, as well as synoptic, thermal, dynamical, seasonal, and geographical features of each cyclone class, indicate dominant processes in their evolution. Among others, the classification reveals the importance of topographically induced Rossby wave breaking to the generation of the most extreme Mediterranean cyclones. These results enhance our understanding of MC predictability by linking the large-scale Rossby wave formations and life cycles to coherent classes of under-predicted cyclone aspects.de Botton Center for Marine ScienceIsraeli Council for Higher Education (CHE)Weizmann Data Science Research CenterWeizmann Institute Sustainability and Energy Research Initiative (SAERI
Parent-offspring conflict and the genetic trade-offs shaping parental investment
The genetic conflict between parents and their offspring is a cornerstone of kin selection theory and the gene-centred view of evolution, but whether it actually occurs in natural systems remains an open question. Conflict operates only if parenting is driven by genetic trade-offs between offspring performance and the parent's ability to raise additional offspring, and its expression critically depends on the shape of these trade-offs. Here we investigate the occurrence and nature of genetic conflict in an insect with maternal care, the earwig Forficula auricularia. Specifically, we test for a direct response to experimental selection on female future reproduction and correlated responses in current offspring survival, developmental rate and growth. The results demonstrate genetic trade-offs that differ in shape before and after hatching. Our study not only provides direct evidence for parent-offspring conflict but also highlights that conflict is not inevitable and critically depends on the genetic trade-offs shaping parental investment.Peer reviewe
Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants.
Dietary intervention with extensively hydrolyzed casein formula supplemented with Lactobacillus rhamnosus GG (EHCF+LGG) accelerates tolerance acquisition in infants with cow's milk allergy (CMA). We examined whether this effect is attributable, at least in part, to an influence on the gut microbiota. Fecal samples from healthy controls (n=20) and from CMA infants (n=19) before and after treatment with EHCF with (n=12) and without (n=7) supplementation with LGG were compared by 16S rRNA-based operational taxonomic unit clustering and oligotyping. Differential feature selection and generalized linear model fitting revealed that the CMA infants have a diverse gut microbial community structure dominated by Lachnospiraceae (20.5±9.7%) and Ruminococcaceae (16.2±9.1%). Blautia, Roseburia and Coprococcus were significantly enriched following treatment with EHCF and LGG, but only one genus, Oscillospira, was significantly different between infants that became tolerant and those that remained allergic. However, most tolerant infants showed a significant increase in fecal butyrate levels, and those taxa that were significantly enriched in these samples, Blautia and Roseburia, exhibited specific strain-level demarcations between tolerant and allergic infants. Our data suggest that EHCF+LGG promotes tolerance in infants with CMA, in part, by influencing the strain-level bacterial community structure of the infant gut
Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs
Non-conding RNAs play a key role in the post-transcriptional regulation of
mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact
with their target RNAs through protein-mediated, sequence-specific binding,
giving rise to extended and highly heterogeneous miRNA-RNA interaction
networks. Within such networks, competition to bind miRNAs can generate an
effective positive coupling between their targets. Competing endogenous RNAs
(ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk.
Albeit potentially weak, ceRNA interactions can occur both dynamically,
affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA
networks as a whole can be implicated in the composition of the cell's
proteome. Many features of ceRNA interactions, including the conditions under
which they become significant, can be unraveled by mathematical and in silico
models. We review the understanding of the ceRNA effect obtained within such
frameworks, focusing on the methods employed to quantify it, its role in the
processing of gene expression noise, and how network topology can determine its
reach.Comment: review article, 29 pages, 7 figure
Dynamic molecular mechanism of the nuclear pore complex permeability barrier
Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport of specific macromolecules while impeding the exchange of unsolicited material. However, key aspects of this gating mechanism remain controversial. To address this issue, we determined the nanoscopic behavior of the permeability barrier directly within yeast S. cerevisiae NPCs at transport-relevant timescales. We show that the large intrinsically disordered domains of phenylalanine-glycine repeat nucleoporins (FG Nups) exhibit highly dynamic fluctuations to create transient voids in the permeability barrier that continuously shape-shift and reseal, resembling a radial polymer brush. Together with cargo-carrying transport factors the FG domains form a feature called the central plug, which is also highly dynamic. Remarkably, NPC mutants with longer FG domains show interweaving meshwork-like behavior that attenuates nucleocytoplasmic transport in vivo. Importantly, the bona fide nanoscale NPC behaviors and morphologies are not recapitulated by in vitro FG domain hydrogels. NPCs also exclude self-assembling FG domain condensates in vivo, thereby indicating that the permeability barrier is not generated by a self-assembling phase condensate, but rather is largely a polymer brush, organized by the NPC scaffold, whose dynamic gating selectivity is strongly enhanced by the presence of transport factors.</p
Effect of promoter architecture on the cell-to-cell variability in gene expression
According to recent experimental evidence, the architecture of a promoter,
defined as the number, strength and regulatory role of the operators that
control the promoter, plays a major role in determining the level of
cell-to-cell variability in gene expression. These quantitative experiments
call for a corresponding modeling effort that addresses the question of how
changes in promoter architecture affect noise in gene expression in a
systematic rather than case-by-case fashion. In this article, we make such a
systematic investigation, based on a simple microscopic model of gene
regulation that incorporates stochastic effects. In particular, we show how
operator strength and operator multiplicity affect this variability. We examine
different modes of transcription factor binding to complex promoters
(cooperative, independent, simultaneous) and how each of these affects the
level of variability in transcription product from cell-to-cell. We propose
that direct comparison between in vivo single-cell experiments and theoretical
predictions for the moments of the probability distribution of mRNA number per
cell can discriminate between different kinetic models of gene regulation.Comment: 35 pages, 6 figures, Submitte
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GTP binding and intramolecular regulation by the ROC domain of Death Associated Protein Kinase 1
The ROCO proteins are a family of large, multidomain proteins characterised by the presence of a Ras of complex proteins (ROC) domain followed by a COR, or C-terminal of ROC, domain. It has previously been shown that the ROC domain of the human ROCO protein Leucine Rich Repeat Kinase 2 (LRRK2) controls its kinase activity. Here, the ability of the ROC domain of another human ROCO protein, Death Associated Protein Kinase 1 (DAPK1), to bind GTP and control its kinase activity has been evaluated. In contrast to LRRK2, loss of GTP binding by DAPK1 does not result in loss of kinase activity, instead acting to modulate this activity. These data highlight the ROC domain of DAPK1 as a target for modifiers of this proteins function, and casts light on the role of ROC domains as intramolecular regulators in complex proteins with implications for a broad range of human diseases
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