Lower female survival from an opportunistic infection reveals progesterone-driven sex bias in trained immunity.

Immune responses differ between females and males, although such sex-based variance is incompletely understood. Observing that bacteremia of the opportunistic pathogen Burkholderia gladioli caused many more deaths of female than male mice bearing genetic deficiencies in adaptive immunity, we determined that this was associated with sex bias in the innate immune memory response called trained immunity. Female attenuation of trained immunity varies with estrous cycle stage and correlates with serum progesterone, a hormone that decreases glycolytic capacity and recall cytokine secretion induced by antigen non-specific stimuli.

Quantitative Biology at Community Colleges, a Network of Biology and Mathematics Faculty Focused on Improving Numerical and Quantitative Skills of Students.

Mastery of quantitative skills is increasingly critical for student success in life sciences, but few curricula adequately incorporate quantitative skills. Quantitative Biology at Community Colleges (QB@CC) is designed to address this need by building a grassroots consortium of community college faculty to 1) engage in interdisciplinary partnerships that increase participant confidence in life science, mathematics, and statistics domains; 2) generate and publish a collection of quantitative skills-focused open education resources (OER); and 3) disseminate these OER and pedagogical practices widely, in turn expanding the network. Currently in its third year, QB@CC has recruited 70 faculty into the network and created 20 modules.

Quantitative imaging and dynamics of tumor therapy with viruses.

Cancer therapy remains challenging due to the myriad presentations of the disease and the vast genetic diversity of tumors that continuously evolve and often become resistant to therapy. Viruses can be engineered to specifically infect, replicate, and kill tumor cells (tumor virotherapy). Moreover, the viruses can be "armed" with therapeutic genes to enhance their oncolytic effect.

Quantification of Protein Interaction Network Dynamics using Multiplexed Co-Immunoprecipitation.

Dynamic protein-protein interactions control cellular behavior, from motility to DNA replication to signal transduction. However, monitoring dynamic interactions among multiple proteins in a protein interaction network is technically difficult. Here, we present a protocol for Quantitative Multiplex Immunoprecipitation (QMI), which allows quantitative assessment of fold changes in protein interactions based on relative fluorescence measurements of Proteins in Shared Complexes detected by Exposed Surface epitopes (PiSCES).

In vitro and in silico multidimensional modeling of oncolytic tumor virotherapy dynamics.

Tumor therapy with replication competent viruses is an exciting approach to cancer eradication where viruses are engineered to specifically infect, replicate, spread and kill tumor cells. The outcome of tumor virotherapy is complex due to the variable interactions between the cancer cell and virus populations as well as the immune response. Oncolytic viruses are highly efficient in killing tumor cells in vitro, especially in a 2D monolayer of tumor cells, their efficiency is significantly lower in a 3D environment, both in vitro and in vivo.

The early proximal αβ TCR signalosome specifies thymic selection outcome through a quantitative protein interaction network.

During αβ T cell development, T cell antigen receptor (TCR) engagement transduces biochemical signals through a protein-protein interaction (PPI) network that dictates dichotomous cell fate decisions. It remains unclear how signal specificity is communicated, instructing either positive selection to advance cell differentiation or death by negative selection. Early signal discrimination might occur by PPI signatures differing qualitatively (customized, unique PPI combinations for each signal), quantitatively (graded amounts of a single PPI series), or kinetically (speed of PPI pathway progression).

Imaging of Oncolytic Measles Virus Propagation with Single-Cell Resolution.

Recombinant measles viruses (MVs) have oncolytic activity against a variety of human cancers. However, their kinetics of spread within tumors has been unexplored. We established an intravital imaging system using the dorsal skin fold chamber, which allows for serial, non-invasive imaging of tumor cells and replication of a fusogenic and a hypofusogenic MV.

Estimation of Oncolytic Virus Populations within Tumors.

The use of replication-competent viruses as oncolytic agents is rapidly expanding, with several oncolytic viruses approved for cancer therapy. As responses to therapy are highly variable, understanding the dynamics of therapy is critical for optimal application of virotherapy in practice. Although mathematical models have been developed to understand the dynamics of tumor virotherapy, a scarcity of data has made difficult parametrization of these models.

Harnessing uncertainty to approximate mechanistic models of interspecific interactions.

Because the Lotka-Volterra competitive equations posit no specific competitive mechanisms, they are exceedingly general, and can theoretically approximate any underlying mechanism of competition near equilibrium. In practice, however, these models rarely generate accurate predictions in diverse communities. We propose that this difference between theory and practice may be caused by how uncertainty propagates through Lotka-Volterra systems.

Gene Expression Signatures Characterized by Longitudinal Stability and Interindividual Variability Delineate Baseline Phenotypic Groups with Distinct Responses to Immune Stimulation.

Human immunity exhibits remarkable heterogeneity among individuals, which engenders variable responses to immune perturbations in human populations. Population studies reveal that, in addition to interindividual heterogeneity, systemic immune signatures display longitudinal stability within individuals, and these signatures may reliably dictate how given individuals respond to immune perturbations. We hypothesize that analyzing relationships among these signatures at the population level may uncover baseline immune phenotypes that correspond with response outcomes to immune stimuli.

Translating Big Data into Smart Data for Veterinary Epidemiology.

The increasing availability and complexity of data has led to new opportunities and challenges in veterinary epidemiology around how to translate abundant, diverse, and rapidly growing "big" data into meaningful insights for animal health. Big data analytics are used to understand health risks and minimize the impact of adverse animal health issues through identifying high-risk populations, combining data or processes acting at multiple scales through epidemiological modeling approaches, and harnessing high velocity data to monitor animal health trends and detect emerging health threats. The advent of big data requires the incorporation of new skills into veterinary epidemiology training, including, for example, machine learning and coding, to prepare a new generation of scientists and practitioners to engage with big data.

An analytical workflow for accurate variant discovery in highly divergent regions.

Background: Current variant discovery methods often start with the mapping of short reads to a reference genome; yet, their performance deteriorates in genomic regions where the reads are highly divergent from the reference sequence. This is particularly problematic for the human leukocyte antigen (HLA) region on chromosome 6p21.3.

Multiplex matrix network analysis of protein complexes in the human TCR signalosome.

Multiprotein complexes transduce cellular signals through extensive interaction networks, but the ability to analyze these networks in cells from small clinical biopsies is limited. To address this, we applied an adaptable multiplex matrix system to physiologically relevant signaling protein complexes isolated from a cell line or from human patient samples. Focusing on the proximal T cell receptor (TCR) signalosome, we assessed 210 pairs of PiSCES (proteins in shared complexes detected by exposed surface epitopes).

A simple method for gene phasing using mate pair sequencing.

Background: Recessive genes cause disease when both copies are affected by mutant loci. Resolving the cis/trans relationship of variations has been an important problem both for researchers, and increasingly, clinicians. Of particular concern are patients who have two heterozygous disease-causing mutations and could be diagnosed as affected (one mutation on each allele) or as phenotypically normal (both mutations on the same allele).

The influence of desmocollin 1-3 expression on prognosis after curative resection of colorectal liver metastases.

Purpose: Prognosis after curative resection of colorectal liver metastases is hard to determine based on clinical parameters; biomarkers are therefore needed. The purpose of this study was to determine the value of desmocollins (DSC) as potential biomarkers. Desmocollins are responsible for cell-cell adhesion in epithelial tissue; their loss may lead to reduced cellular adhesion and facilitate cellular migration, enabling tumor cells to form distant metastases.

Toward a mechanistic understanding of how natural bacterial communities respond to changes in temperature in aquatic ecosystems.

We examine how heterotrophic bacterioplankton communities respond to temperature by mathematically defining two thermally adapted species and showing how changes in environmental temperature affect competitive outcome in a two-resource environment. We did this by adding temperature dependence to both the respiration and uptake terms of a two species, two-resource model rooted in Droop kinetics. We used published literature values and results of our own work with experimental microcosms to parameterize the model and to quantitatively and qualitatively define relationships between temperature and bacterioplankton physiology.

Patch aging and the S-Allee effect: breeding system effects on the demographic response of plants to habitat fragmentation.

We used empirical and modeling approaches to examine effects of plant breeding systems on demographic responses to habitat fragmentation. Empirically, we investigated effects of local flowering plant density on pollination and of population size on mate availability in a common, self-incompatible purple coneflower, Echinacea angustifolia, growing in fragmented prairie habitat. Pollination and recruitment increased with weighted local density around individual flowering plants.

Local migration promotes competitive restraint in a host-pathogen 'tragedy of the commons'.

Fragmented populations possess an intriguing duplicity: even if subpopulations are reliably extinction-prone, asynchrony in local extinctions and recolonizations makes global persistence possible. Migration is a double-edged sword in such cases: too little migration prevents recolonization of extinct patches, whereas too much synchronizes subpopulations, raising the likelihood of global extinction. Both edges of this proverbial sword have been explored by manipulating the rate of migration within experimental populations.

Spatial dynamics in model plant communities: what do we really know?

A variety of models have shown that spatial dynamics and small-scale endogenous heterogeneity (e.g., forest gaps or local resource depletion zones) can change the rate and outcome of competition in communities of plants or other sessile organisms.

Founder control and coexistence in a simple model of asymmetric competition for light.

Size asymmetry in plant light acquisition complicates predictions of competitive outcomes in light-limited communities. We present a mathematically tractable model of asymmetric competition for light and discuss its implications for predicting outcomes of competition during establishment in two-, three-, and many-species communities. In contrast to the resource-reduction model of symmetric competition for a single resource, the model we present predicts that outcomes of asymmetric competition for light will sometimes depend on the timing of establishment and the consequent hierarchy among species in canopy position.

The pattern of amino acid replacements in alpha/beta-barrels.

The determinants of site-to-site variability in the rate of amino acid replacement in alpha/beta-barrel enzyme structures are investigated. Of 125 available alpha/beta-barrel structures, only 25 meet a variety of phylogenetic and statistical criteria necessary to ensure sufficient data for reliable analysis. These 25 enzyme structures (from a wide variety of taxa with diverse lifestyles in diverse habitats) differ greatly in size, number, and topology of domains in addition to the alpha/beta-barrel, quaternary structure, metabolic role, reaction catalyzed, presence of prosthetic groups, regulatory mechanisms, use of cofactors, and catalytic mechanisms.