114 research outputs found
RhoE Deficiency Produces Postnatal Lethality, Profound Motor Deficits and Neurodevelopmental Delay in Mice
Rnd proteins are a subfamily of Rho GTPases involved in the control of actin cytoskeleton dynamics and other cell functions such as motility, proliferation and survival. Unlike other members of the Rho family, Rnd proteins lack GTPase activity and therefore remain constitutively active. We have recently described that RhoE/Rnd3 is expressed in the Central Nervous System and that it has a role in promoting neurite formation. Despite their possible relevance during development, the role of Rnd proteins in vivo is not known. To get insight into the in vivo function of RhoE we have generated mice lacking RhoE expression by an exon trapping cassette. RhoE null mice (RhoE gt/gt) are smaller at birth, display growth retardation and early postnatal death since only half of RhoE gt/gt mice survive beyond postnatal day (PD) 15 and 100% are dead by PD 29. RhoE gt/gt mice show an abnormal body position with profound motor impairment and impaired performance in most neurobehavioral tests. Null mutant mice are hypoactive, show an immature locomotor pattern and display a significant delay in the appearance of the hindlimb mature responses. Moreover, they perform worse than the control littermates in the wire suspension, vertical climbing and clinging, righting reflex and negative geotaxis tests. Also, RhoE ablation results in a delay of neuromuscular maturation and in a reduction in the number of spinal motor neurons. Finally, RhoE gt/gt mice lack the common peroneal nerve and, consequently, show a complete atrophy of the target muscles. This is the first model to study the in vivo functions of a member of the Rnd subfamily of proteins, revealing the important role of Rnd3/RhoE in the normal development and suggesting the possible involvement of this protein in neurological disorders
Digital Health Europe (DHE) Twinning on Severe AsthmaâKick-off Meeting Report
info:eu-repo/semantics/publishedVersio
A Large Change in Temperature between Neighbouring Days Increases the Risk of Mortality
Background: Previous studies have found high temperatures increase the risk of mortality in summer. However, little is known about whether a sharp decrease or increase in temperature between neighbouring days has any effect on mortality. Method: Poisson regression models were used to estimate the association between temperature change and mortality in summer in Brisbane, Australia during 1996â2004 and Los Angeles, United States during 1987â2000. The temperature change was calculated as the current dayâs mean temperature minus the previous dayâs mean. Results: In Brisbane, a drop of more than 3 °C in temperature between days was associated with relative risks (RRs) of 1.157 (95% confidence interval (CI): 1.024, 1.307) for total non external mortality (NEM), 1.186 (95%CI: 1.002, 1.405) for NEM in females, and 1.442 (95%CI: 1.099, 1.892) for people aged 65â74 years. An increase of more than 3 °C was associated with RRs of 1.353 (95%CI: 1.033, 1.772) for cardiovascular mortality and 1.667 (95%CI: 1.146, 2.425) for people aged < 65 years. In Los Angeles, only a drop of more than 3 °C was significantly associated with RRs of 1.133 (95%CI: 1.053, 1.219) for total NEM, 1.252 (95%CI: 1.131, 1.386) for cardiovascular mortality, and 1.254 (95%CI: 1.135, 1.385) for people aged â„75 years. In both cities, there were joint effects of temperature change and mean temperature on NEM. Conclusion : A significant change in temperature of more than 3 °C, whether positive or negative, has an adverse impact on mortality even after controlling for the current temperature
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Changes in northern hemisphere temperature variability shaped by regional warming patterns
Global warming involves changes not only in the mean atmospheric temperature, but also in its variability and extremes. Here we use a feature-tracking technique to investigate the dynamical contribution to temperature anomalies in the northern hemisphere in CMIP5 climate-change simulations. We develop a simple theory to explain how temperature variance and skewness changes are generated dynamically from mean temperature gradient changes, and demonstrate the crucial role of regional warming patterns in shaping the distinct response of cold and warm anomalies. We also show that skewness changes must be taken into account, in addition to variance changes, in order to correctly capture the projected temperature variability response. These changes in variability may impact humans, agriculture and animals, as they experience not only a warmer mean climate, but also a new likelihood of temperature anomalies within that climate
Peripheral blood T-cell signatures from high-resolution immune phenotyping of γΎ and αÎČ T-cells in younger and older subjects in the Berlin Aging Study II
Background Aging and latent infection with Cytomegalovirus (CMV) are thought
to be major factors driving the immune system towards immunosenescence,
primarily characterized by reduced amounts of naĂŻve T-cells and increased
memory T-cells, potentially associated with higher morbidity and mortality.
The composition of both major compartments, γΎ as well as αÎČ T-cells, is
altered by age and CMV, but detailed knowledge of changes to the γΎ subset is
currently limited. Results Here, we have surveyed a population of 73 younger
(23â35 years) and 144 older (62â85 years) individuals drawn from the Berlin
Aging Study II, investigating the distribution of detailed differentiation
phenotypes of both γΎ and αÎČ T-cells. Correlation of frequencies and absolute
counts of the identified phenotypes with age and the presence of CMV revealed
a lower abundance of VÎŽ2-positive and a higher amount of VÎŽ1-positive cells.
We found higher frequencies of late-differentiated and lower frequencies of
early-differentiated cells in the VÎŽ1+ and VÎŽ1-VÎŽ2-, but not in the VÎŽ2+
populations in elderly CMV-seropositive individuals confirming the association
of these VÎŽ2-negative cells with CMV-immunosurveillance. We identified the
highest VÎŽ1:VÎŽ2 ratios in the CMV-seropositive elderly. The observed increased
CD4:CD8 ratios in the elderly were significantly lower in CMV-seropositive
individuals, who also possessed a lower naĂŻve and a larger late-differentiated
compartment of CD8+ αÎČ T-cells, reflecting the consensus in the literature.
Conclusions Our findings illustrate in detail the strong influence of CMV on
the abundance and differentiation pattern of γΎ T-cells as well as αÎČ T-cells
in older and younger people. Mechanisms responsible for the phenotypic
alterations in the γΎ T-cell compartment, associated both with the presence of
CMV and with age require further clarification
Assessment and prevention of acute health effects of weather conditions in Europe, the PHEWE project: background, objectives, design
<p>Abstract</p> <p>Background</p> <p>The project "Assessment and prevention of acute health effects of weather conditions in Europe" (PHEWE) had the aim of assessing the association between weather conditions and acute health effects, during both warm and cold seasons in 16 European cities with widely differing climatic conditions and to provide information for public health policies.</p> <p>Methods</p> <p>The PHEWE project was a three-year pan-European collaboration between epidemiologists, meteorologists and experts in public health. Meteorological, air pollution and mortality data from 16 cities and hospital admission data from 12 cities were available from 1990 to 2000. The short-term effect on mortality/morbidity was evaluated through city-specific and pooled time series analysis. The interaction between weather and air pollutants was evaluated and health impact assessments were performed to quantify the effect on the different populations. A heat/health watch warning system to predict oppressive weather conditions and alert the population was developed in a subgroup of cities and information on existing prevention policies and of adaptive strategies was gathered.</p> <p>Results</p> <p>Main results were presented in a symposium at the conference of the International Society of Environmental Epidemiology in Paris on September 6<sup>th </sup>2006 and will be published as scientific articles. The present article introduces the project and includes a description of the database and the framework of the applied methodology.</p> <p>Conclusion</p> <p>The PHEWE project offers the opportunity to investigate the relationship between temperature and mortality in 16 European cities, representing a wide range of climatic, socio-demographic and cultural characteristics; the use of a standardized methodology allows for direct comparison between cities.</p
Short Term Depression Unmasks the Ghost Frequency
Short Term Plasticity (STP) has been shown to exist extensively in synapses throughout the brain. Its function is more or less clear in the sense that it alters the probability of synaptic transmission at short time scales. However, it is still unclear what effect STP has on the dynamics of neural networks. We show, using a novel dynamic STP model, that Short Term Depression (STD) can affect the phase of frequency coded input such that small networks can perform temporal signal summation and determination with high accuracy. We show that this property of STD can readily solve the problem of the ghost frequency, the perceived pitch of a harmonic complex in absence of the base frequency. Additionally, we demonstrate that this property can explain dynamics in larger networks. By means of two models, one of chopper neurons in the Ventral Cochlear Nucleus and one of a cortical microcircuit with inhibitory Martinotti neurons, it is shown that the dynamics in these microcircuits can reliably be reproduced using STP. Our model of STP gives important insights into the potential roles of STP in self-regulation of cortical activity and long-range afferent input in neuronal microcircuits
Transcriptional program for nitrogen starvation-induced lipid accumulation in Chlamydomonas reinhardtii
Perception of nursing students about couples' violence: knowledge, beliefs and professional role
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field
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