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Wolf, B.

Publications and source records attributed to Wolf, B..

4 recordsLinked to original sources

Neuraminidase activity mediates IL-6 production through TLR4 and p38/ERK MAPK signaling in MRL/lpr mesangial cells

Mesangial cells (MCs), considered the immune cell of the kidney, secrete a number of cytokines including IL-6, which serves as an autocrine factor for MCs stimulating proliferation. IL-6 is associated with disease in patients and mouse strains with lupus nephritis, promoting tissue damage. Previously, we demonstrated the activity or levels of the enzyme neuraminidase (NEU) is increased in the kidneys of lupus mice and urine of human patients with nephritis and that NEU activity plays a role in mediating IL-6 secretion from lupus prone MRL/lpr primary mouse MCs. In this study, we further elucidate the mechanisms by which NEU activity mediates cytokine production by primary lupus prone MCs. MRL/lpr primary MCs were cultured with lupus serum to stimulate cytokine production in the absence or presence of NEU activity inhibitor. Our results show lupus serum increases NEU activity, and secretion of GM-CSF and MIP1, in addition to IL-6, is significantly reduced when NEU activity is inhibited. mRNA expression of Il-6 and Gm-csf was also increased in response to lupus serum, and reduced when NEU activity was inhibited. Using neutralizing antibodies to specific receptors, inhibitors of MAP kinase signaling pathways, and LPS stimulation we show TLR4 and p38/ERK MAPK play a role in NEU-mediated secretion of IL-6. Together, our results suggest NEU activity plays an important role in the response of lupus prone MCs to factor(s) in lupus serum that stimulates IL-6 expression and secretion through TLR4-p38/ERK MAPK signaling, likely through desialyation of one or more glycoproteins in this pathway.

cell biology

A sparse occupancy model to quantify species interactions in time and space

Camera traps and acoustic recording devices are essential tools to quantify the distribution, abundance and behavior of mobile species. Varying detection probabilities among device locations must be accounted for when analyzing such data, which is generally done using occupancy models. We introduce a Bayesian Time-dependent Observation Model for Camera Trap data (Tomcat), suited to estimate relative event densities in space and time. Tomcat allows to learn about the environmental requirements and daily activity patterns of species while accounting for imperfect detection. It further implements a sparse model that deals well will a large number of potentially highly correlated environmental variables. By integrating both spatial and temporal information, we extend the notation of overlap coefficient between species to time and space to study niche partitioning. We illustrate the power of Tomcat through an application to camera trap data of eight sympatrically occurring duiker Cephalophinae species in the savanna - rainforest ecotone in the Central African Republic and show that most species pairs show little overlap. Exceptions are those for which one species is very rare, likely as a result of direct competition.

ecology

Detecting selection from linked sites using an F-model

Allele frequencies vary across populations and loci, even in the presence of migration. While most differences may be due to genetic drift, divergent selection will further increase differentiation at some loci. Identifying those is key in studying local adaptation, but remains statistically challenging. A particularly elegant way to describe allele frequency differences among populations connected by migration is the F-model, which measures differences in allele frequencies by population specific FST coefficients. This model readily accounts for multiple evolutionary forces by partitioning FST coefficients into locus and population specific components reflecting selection and drift, respectively. Here we present an extension of this model to linked loci by means of a hidden Markov model (HMM) that characterizes the effect of selection on linked markers through correlations in the locus specific component along the genome. Using extensive simulations we show that our method has up to two-fold the statistical power of previous implementations that assume sites to be independent. We finally evidence selection in the human genome by applying our method to data from the Human Genome Diversity Project (HGDP).

genomics

Metabolic rate is negatively linked to adult survival but does not explain latitudinal differences in songbirds

Survival rates vary dramatically among species and predictably across latitudes, but causes of this variation are unclear. The rate of living hypothesis posits that physiological damage from metabolism causes species with faster metabolic rates to exhibit lower survival rates. However, whether increased survival commonly observed in tropical and south temperate latitudes is associated with slower metabolic rate remains unclear. We compared metabolic rates and annual survival rates across 46 species that we measured, and 147 species from literature data across northern, southern, and tropical latitudes. High metabolic rates were associated with lower survival but latitude had substantial direct effects on survival independent of metabolism. The inability of metabolic rate to explain latitudinal variation in survival suggests 1) that species may evolve physiological mechanisms that mitigate physiological damage from cellular metabolism, and 2) a larger role of extrinsic environmental, rather than intrinsic metabolic, causes of latitudinal differences in mortality.

evolutionary biology