Lower Neighborhood Socioeconomic Status Associated with Reduced Diversity of the Colonic Microbiota in Healthy Adults

In the United States, there are persistent and widening socioeconomic gaps in morbidity and mortality from chronic diseases. Although most disparities research focuses on person-level socioeconomic-status, mounting evidence suggest that chronic diseases also pattern by the demographic characteristics of neighborhoods. Yet the biological mechanisms underlying these associations are poorly understood. There is increasing recognition that chronic diseases share common pathogenic features, some of which involve alterations in the composition, diversity, and functioning of the gut microbiota. This study examined whether socioeconomic-status was associated with alpha-diversity of the colonic microbiota. Forty-four healthy adults underwent un-prepped sigmoidoscopy, during which mucosal biopsies and fecal samples were collected. Subjects’ zip codes were geocoded, and census data was used to form a composite indicator of neighborhood socioeconomic-status, reflecting household income, educational attainment, employment status, and home value. In unadjusted analyses, neighborhood socioeconomic-status explained 12–18 percent of the variability in alpha-diversity of colonic microbiota. The direction of these associations was positive, meaning that as neighborhood socioeconomic-status increased, so did alpha-diversity of both the colonic sigmoid mucosa and fecal microbiota. The strength of these associations persisted when models were expanded to include covariates reflecting potential demographic (age, gender, race/ethnicity) and lifestyle (adiposity, alcohol use, smoking) confounds. In these models neighborhood socioeconomic-status continued to explain 11–22 percent of the variability in diversity indicators. Further analyses suggested these patterns reflected socioeconomic variations in evenness, but not richness, of microbial communities residing in the sigmoid. We also found indications that residence in neighborhoods of higher socioeconomic-status was associated with a greater abundance of Bacteroides and a lower abundance of Prevotella, suggesting that diet potentially underlies differences in microbiota composition. These findings suggest the presence of socioeconomic variations in colonic microbiota diversity. Future research should explore whether these variations contribute to disparities in chronic disease outcomes.     

Contrasting patterns of density‐dependent selection at different life stages can create more than one fast–slow axis of life‐history variation

There has been much recent research interest in the existence of a major axis of life‐history variation along a fast–slow continuum within almost all major taxonomic groups. Eco‐evolutionary models of density‐dependent selection provide a general explanation for such observations of interspecific variation in the "pace of life." One issue, however, is that some large‐bodied long‐lived “slow” species (e.g., trees and large fish) often show an explosive “fast” type of reproduction with many small offspring, and species with “fast” adult life stages can have comparatively “slow” offspring life stages (e.g., mayflies). We attempt to explain such life‐history evolution using the same eco‐evolutionary modeling approach but with two life stages, separating adult reproductive strategies from offspring survival strategies. When the population dynamics in the two life stages are closely linked and affect each other, density‐dependent selection occurs in parallel on both reproduction and survival, producing the usual one‐dimensional fast–slow continuum (e.g., houseflies to blue whales). However, strong density dependence at either the adult reproduction or offspring survival life stage creates quasi‐independent population dynamics, allowing fast‐type reproduction alongside slow‐type survival (e.g., trees and large fish), or the perhaps rarer slow‐type reproduction alongside fast‐type survival (e.g., mayflies—short‐lived adults producing few long‐lived offspring). Therefore, most types of species life histories in nature can potentially be explained via the eco‐evolutionary consequences of density‐dependent selection given the possible separation of demographic effects at different life stages.     

Investigation of the dithiocarbamate-induced coupling of allylidene and carbonyl ligands on a tungsten center

Reaction of the allylidene tungsten complex [W(CPhCHCHMe)Br₂(CO)₂(4-picoline)] (1) with the dithiocarbamates MS₂CNR₂ (a: M=Na, R=Et; b: M=Na, R=Me; c: M=Li, R=Ph) in THF at 50 °C affords the vinylketene tungsten complexes [W(S₂CNR₂)₂(OCCPhCHCHMe)(CO)] (2a–c). At lower temperatures, four reaction intermediates (3–6) may be discerned. Spectroscopic studies indicate that these compounds contain η⁴-allyldithiocarbamate ligands which are generated by addition of dithiocarbamate across the metal-carbon double bond of the allylidene-tungsten unit in 1. The structures of [W(S₂CNEt₂)₂(OCCPhCHCHMe)(CO)] (2a) and of one intermediate, [W(η⁴-Et₂NCS₂CPhCHCHMe)(S₂CNEt₂)(CO)₂] (5a) were elucidated by X-ray crystallography.     

Behavioural method to detect marginal neurotoxic effects of ivermectin in DA/Orl rats.

Ivermectin (22, 23-dihydroavermectin B 1) in subtoxic doses was administered subcutaneously to young adult DA rats. Prior to treatment the rats had been trained in a visual discrimination learning programme until their response pattern was stable. The behavioural response data were recorded during continued discrimination testing following the Ivermectin injection and compared with those of a control group. The results showed that the Ivermectin injection reduced the total number of lever presses and reinforcement collections. Further the treatment caused an increase in the total number of erroneous responses.     

New monogeneans from the bathydemersal southern African endemic catshark,Holohalaelurus regani (Gilchrist, 1922)

The catshark genus Holohalaelurus Fowler is currently represented by five species distributed off the southern and eastern parts of the African coast. Very few parasitological records exist for any of these five species, representing a significant knowledge gap. We report the first monogenean species from the bathydemersal species Holohalaelurus regani (Gilchrist): a new species of Microbothriidae Price, 1936, Leptomicrobothrium holohalaelure n. sp. from the dorsal skin surface, and a new species of Hexabothriidae Price, 1942 representing a new genus, Scyliorhinocotyle narvaezae n. gen., n. sp., from the gill lamellae. Both monogenean records represent the first for any member of the catshark genus Holohalaelurus. Previously we focused on the identification of monogenean taxa of emerging veterinary importance for public aquaria. We now begin a focused effort to document a generally unexplored monogenean biodiversity from diverse marine habitats off South Africa.

     

Dynamic Allostery Mediated by a Conserved Tryptophan in the Tec Family Kinases

Bruton’s tyrosine kinase (Btk) is a Tec family non-receptor tyrosine kinase that plays a critical role in immune signaling and is associated with the immunological disorder X-linked agammaglobulinemia (XLA). Our previous findings showed that the Tec kinases are allosterically activated by the adjacent N-terminal linker. A single tryptophan residue in the N-terminal 17-residue linker mediates allosteric activation, and its mutation to alanine leads to the complete loss of activity. Guided by hydrogen/deuterium exchange mass spectrometry results, we have employed Molecular Dynamics simulations, Principal Component Analysis, Community Analysis and measures of node centrality to understand the details of how a single tryptophan mediates allostery in Btk. A specific tryptophan side chain rotamer promotes the functional dynamic allostery by inducing coordinated motions that spread across the kinase domain. Either a shift in the rotamer population, or a loss of the tryptophan side chain by mutation, drastically changes the coordinated motions and dynamically isolates catalytically important regions of the kinase domain. This work also identifies a new set of residues in the Btk kinase domain with high node centrality values indicating their importance in transmission of dynamics essential for kinase activation. Structurally, these node residues appear in both lobes of the kinase domain. In the N-lobe, high centrality residues wrap around the ATP binding pocket connecting previously described Catalytic-spine residues. In the C-lobe, two high centrality node residues connect the base of the R- and C-spines on the αF-helix. We suggest that the bridging residues that connect the catalytic and regulatory architecture within the kinase domain may be a crucial element in transmitting information about regulatory spine assembly to the catalytic machinery of the catalytic spine and active site.     

Pattern of variation in avian population growth rates

A central question in population ecology is to understand why population growth rates differ over time. Here, we describe how the long-term growth of populations is not only influenced by parameters affecting the expected dynamics, for example form of density dependence and specific population growth rate, but is also affected by environmental and demographic stochasticity. Using long-term studies of fluctuations of bird populations, we show an interaction between the stochastic and the deterministic components of the population dynamics: high specific growth rates at small densities r(1) are typically positively correlated with the environmental variance sigma(e)(2). Furthermore, theta, a single parameter describing the form of the density regulation in the theta-logistic density-regulation model, is negatively correlated with r(1). These patterns are in turn correlated with interspecific differences in life-history characteristics. Higher specific growth rates, larger stochastic effects on the population dynamics and stronger density regulation at small densities are found in species with large clutch sizes or high adult mortality rates than in long-lived species. Unfortunately, large uncertainties in parameter estimates, as well as strong stochastic effects on the population dynamics, will often make even short-term population projections unreliable. We illustrate that the concept of population prediction interval can be useful in evaluating the consequences of these uncertainties in the population projections for the choice of management actions.     

Estimating density dependence in time-series of age-structured populations

For a life history with age at maturity alpha, and stochasticity and density dependence in adult recruitment and mortality, we derive a linearized autoregressive equation with time-lags of from 1 to alpha years. Contrary to current interpretations, the coefficients for different time-lags in the autoregressive dynamics do not simply measure delayed density dependence, but also depend on life-history parameters. We define a new measure of total density dependence in a life history, D, as the negative elasticity of population growth rate per generation with respect to change in population size, D = - partial differential lnlambda(T)/partial differential lnN, where lambda is the asymptotic multiplicative growth rate per year, T is the generation time and N is adult population size. We show that D can be estimated from the sum of the autoregression coefficients. We estimated D in populations of six avian species for which life-history data and unusually long time-series of complete population censuses were available. Estimates of D were in the order of 1 or higher, indicating strong, statistically significant density dependence in four of the six species.