Genomic variation and strain-specific functional adaptation in the human gut microbiome during early life

The human gut microbiome matures towards the adult composition during the first years of life and is implicated in early immune development. Here, we investigate the effects of microbial genomic diversity on gut microbiome development using integrated early childhood data sets collected in the DIABIMMUNE study in Finland, Estonia and Russian Karelia. We show that gut microbial diversity is associated with household location and linear growth of children. Single nucleotide polymorphism- and metagenomic assembly-based strain tracking revealed large and highly dynamic microbial pangenomes, especially in the genus Bacteroides, in which we identified evidence of variability deriving from Bacteroides-targeting bacteriophages. Our analyses revealed functional consequences of strain diversity; only 10% of Finnish infants harboured Bifidobacterium longum subsp. infantis, a subspecies specialized in human milk metabolism, whereas Russian infants commonly maintained a probiotic Bifidobacterium bifidum strain in infancy. Groups of bacteria contributing to diverse, characterized metabolic pathways converged to highly subject-specific configurations over the first two years of life. This longitudinal study extends the current view of early gut microbial community assembly based on strain-level genomic variation.Peer reviewe

Signaling Mechanisms of Vav3, a Guanine Nucleotide Exchange Factor and Androgen Receptor Coactivator, in Physiology and Prostate Cancer Progression

The Rho GTPase guanine nucleotide exchange factor (GEF) Vav3 is the third member of the Vavfamily of GEFS and is activated by tyrosine phosphorylation. Through stimulation of Rho GTPaseactivity, Vav3 promotes cell migration, invasion, and other cellular processes. Work from our laboratory first established that Vav3 is upregulated in models of castration-resistant prostate cancer progression and enhances androgen receptor as well as androgen receptor splice variant activity. Recent analysis of clinical specimens supports Vav3 as a potential biomarker of aggressive prostate cancer. Consistent with a role in promoting castration-­resistant disease, Vav3 is a versatile enhancer of androgen receptor by both ligand-dependent and ligand-independent mechanisms and as such impacts established pathways of androgen receptor reactivation in advanced prostate cancer. Distinct Vav3 domains and mechanisms participate in ligand-dependent and -independent androgen receptor coactivation. To provide a physiologic context, we review Vav3 actions elucidated by gene knockout studies. This chapter describes the pervasive role of Vav3 in progression of prostate cancer to castration resistance. We discuss the mechanisms by which prostate cancer cells exploit Vav3 signaling to promote androgen receptor activity under different hormonal milieus, which are relevant to clinical prostate cancer. Lastly, we review the data on the emerging role for Vav3 in other cancers ranging from leukemias to gliomas.https://nsuworks.nova.edu/hpd_medsci_faculty_books/1002/thumbnail.jp

Differential In Vitro Effects of Intravenous versus Oral Formulations of Silibinin on the HCV Life Cycle and Inflammation

Silymarin prevents liver disease in many experimental rodent models, and is the most popular botanical medicine consumed by patients with hepatitis C. Silibinin is a major component of silymarin, consisting of the flavonolignans silybin A and silybin B, which are insoluble in aqueous solution. A chemically modified and soluble version of silibinin, SIL, has been shown to potently reduce hepatitis C virus (HCV) RNA levels in vivo when administered intravenously. Silymarin and silibinin inhibit HCV infection in cell culture by targeting multiple steps in the virus lifecycle. We tested the hepatoprotective profiles of SIL and silibinin in assays that measure antiviral and anti-inflammatory functions. Both mixtures inhibited fusion of HCV pseudoparticles (HCVpp) with fluorescent liposomes in a dose-dependent fashion. SIL inhibited 5 clinical genotype 1b isolates of NS5B RNA dependent RNA polymerase (RdRp) activity better than silibinin, with IC50 values of 40–85 µM. The enhanced activity of SIL may have been in part due to inhibition of NS5B binding to RNA templates. However, inhibition of the RdRps by both mixtures plateaued at 43–73%, suggesting that the products are poor overall inhibitors of RdRp. Silibinin did not inhibit HCV replication in subgenomic genotype 1b or 2a replicon cell lines, but it did inhibit JFH-1 infection. In contrast, SIL inhibited 1b but not 2a subgenomic replicons and also inhibited JFH-1 infection. Both mixtures inhibited production of progeny virus particles. Silibinin but not SIL inhibited NF-κB- and IFN-B-dependent transcription in Huh7 cells. However, both mixtures inhibited T cell proliferation to similar degrees. These data underscore the differences and similarities between the intravenous and oral formulations of silibinin, which could influence the clinical effects of this mixture on patients with chronic liver diseases

What jobs are Winthrop College of Business Students Searching for?

The purpose of this study is to understand what jobs Winthrop college students are looking for upon entering the workforce. Using a quantitative survey methodology sampling students from Winthrop college of business, we tested hypotheses regarding the determinants of choosing hybrid jobs, in person jobs, or a hybrid work situation. Data will be analyzed using descriptive statistics, correction, and regression analysis. Although data collection is still underway, the results of this study have the potential to inform business practices around what college students are looking for and allow us to understand the wants and needs of potential employees

Low rates of rock organic carbon oxidation and anthropogenic cycling of rhenium in a slowly denuding landscape

The oxidation of petrogenic organic carbon (OCpetro) is a source of carbon dioxide to the atmosphere over geological timescales. The rates of OCpetro oxidation in locations that experience low rates of denudation remain poorly constrained, despite these landscapes dominating Earth’s continental surface area. Here, we track OCpetro oxidation using radiocarbon and the trace element rhenium (Re) in the deep weathering profiles, soils and stream waters of the Susquehanna Shale Hills Critical Zone Observatory (PA, USA). In a ridge-top borehole, radiocarbon measurements reveal the presence of a broad OCpetro weathering front, with a first order assessment of ~40% loss occurring over ~6 m. However, the low OCpetro concentration (80% of Re in the rock is associated with OCpetro, based on Re/Na and Re/S ratios. Using estimates of long-term denudation rates, the observed OCpetro loss and the Re proxy are equivalent to a low OCpetro oxidation yield of <1.7×10-2 tC km-2 yr-1. This is consistent with the low OCpetro concentrations and low denudation rates at this location. In addition, we find the surface cycle of Re is decoupled from that of deep weathering, with an enrichment of Re in surface soils and elevated Re concentrations in stream water, precipitation, and shallow groundwater. A mass balance model shows that this can be explained by a historical anthropogenic contribution of Re through atmospheric deposition. We estimate that the topsoil Re pool could take decades to centuries to deplete and call for a renewed focus on anthropogenic perturbation of the surface Re cycle in low denudation rate settings

Magnesium isotope fractionation during shale weathering in the Shale Hills Critical Zone Observatory: Accumulation of light Mg isotopes in soils by clay mineral transformation

Magnesium isotopic ratios have been used as a natural tracer to study weathering processes and biogeochemical pathways in surficial environments, but few have focused on the mechanisms that control Mg isotope fractionation during shale weathering. In this study we focus on understanding Mg isotope fractionation in the Shale Hills catchment in central Pennsylvania. Mg isotope ratios were measured systematically in weathering products, along geochemical pathways of Mg during shale weathering: from bedrock to soils and soil pore water on a planar hillslope, and to sediments, stream water, and groundwater on a valley floor. Significant variations of Mg isotopic values were observed: δ26Mg values (− 0.6‰ to − 0.1‰) of stream and soil pore waters are about ~ 0.5‰ to 1‰ lighter than the shale bedrock δ(26Mg values of + 0.4‰), consistent with previous observations that lighter Mg isotopes are preferentially released to water during silicate weathering. Dissolution of the carbonate mineral ankerite, depleted in the shallow soils but present in bedrock at greater depths, produced higher Mg2 + concentrations but lower δ26Mg values (− 1.1‰) in groundwater, ~ 1.5‰ lighter than the bedrock. δ26Mg values (+ 0.2‰ to + 0.4‰) of soil samples on the planar hillslope are either similar or up to ~ 0.2‰ lighter than the bedrock. Hence a heavy Mg isotope reservoir – complementary to the lighter Mg isotopes in soil pore water and stream water – is missing from the residual soils on the hillslope. In addition, soil samples show a slight but systematic decreasing trend in δ26Mg values with increasing weathering duration towards the surface. We suggest that the accumulation of light Mg isotopes in surface soils at Shale Hills is due to a combined effect of i) sequestration of isotopically light Mg from soil water during clay dissolution–precipitation reactions; and ii) loss of isotopically heavy particulate Mg in micron-sized particles from the hillslope as suspended sediments. This latter mechanism is somewhat surprising in that most researchers do not consider physical removal or particles to be a likely mechanism of isotopic fractionation. Stream sediments (δ26Mg values of + 0.3‰ to + 0.5‰) accumulated on the valley floor are ~ 0.2‰ heavier than the bedrock, and are thus consistent with that mobile particulates are the heavy Mg isotope reservoir. Our study provides the first field evidence that changes in clay mineralogy lead to accumulation of lighter Mg isotopes in residual bulk soils. This example also demonstrates that transport of isotopically distinct fine particles from clay-rich systems could be a new and important mechanism to drive the Mg isotope compositions of silicate weathering residuals. This mechanism drives fractionation in an opposite direction as might be expected from previous studies, i.e. residual soils are driven to lighter Mg values and sediments become isotopically heavier

Hurricanes and Typhoons

Tropical cyclones represent one of nature’s most destructive forces and the effects of climate variability and continued coastal development are likely to exacerbate these impacts. Disasters and disaster recovery will depend heavily on improved predictions over short time intervals for evacuation decision-making and over many years for community planning and development of resilient coastal areas for natural and urban landscapes (Brantley et al., 2014; Sealza and Sealza, 2014). These storms are fundamentally a heat engine taking energy from the sea via the latent heat of evaporation and depositing the energy at mid-tropospheric levels via condensation. This engine converts the heat energy directly into mechanical energy (winds, waves and currents). Potential positive feedbacks, related to the dependence of evaporation rates on wind speed and storm intensity and mid-tropospheric heating rates, exist in this system. Therefore, tropical cyclones will continued to strengthen in ocean areas with high water temperatures, minimal vertical shear, and moist air aloft until the mechanical and heat energy losses equal the heat sources