Different Selective Pressures Lead to Different Genomic Outcomes as Newly-Formed Hybrid Yeasts Evolve

Background: Interspecific hybridization occurs in every eukaryotic kingdom. While hybrid progeny are frequently at a selective disadvantage, in some instances their increased genome size and complexity may result in greater stress resistance than their ancestors, which can be adaptively advantageous at the edges of their ancestors\u27 ranges. While this phenomenon has been repeatedly documented in the field, the response of hybrid populations to long-term selection has not often been explored in the lab. To fill this knowledge gap we crossed the two most distantly related members of the Saccharomyces sensu stricto group, S. cerevisiae and S. uvarum, and established a mixed population of homoploid and aneuploid hybrids to study how different types of selection impact hybrid genome structure. Results: As temperature was raised incrementally from 31 degrees C to 46.5 degrees C over 500 generations of continuous culture, selection favored loss of the S. uvarum genome, although the kinetics of genome loss differed among independent replicates. Temperature-selected isolates exhibited greater inherent and induced thermal tolerance than parental species and founding hybrids, and also exhibited ethanol resistance. In contrast, as exogenous ethanol was increased from 0% to 14% over 500 generations of continuous culture, selection favored euploid S. cerevisiae x S. uvarum hybrids. Ethanol-selected isolates were more ethanol tolerant than S. uvarum and one of the founding hybrids, but did not exhibit resistance to temperature stress. Relative to parental and founding hybrids, temperature-selected strains showed heritable differences in cell wall structure in the forms of increased resistance to zymolyase digestion and Micafungin, which targets cell wall biosynthesis. Conclusions: This is the first study to show experimentally that the genomic fate of newly-formed interspecific hybrids depends on the type of selection they encounter during the course of evolution, underscoring the importance of the ecological theatre in determining the outcome of the evolutionary play

Innovation highway Breakthrough milestones amp; key developments in chalcopyrite photovoltaics from a retrospective viewpoint

The present contribution is a summary of an event that was organized as a special evening session in Symposium V Chalcogenide Thin Film Solar Cells at the E MRS 2016 Spring Meeting, Lille, France. The presentations in this session were given by the coauthors of this paper. These authors present retrospectives of key developments in the amp; 64257;eld of Cu In,Ga S,Se 2 solar cells as they themselves had witnessed in their laboratories or companies. Also, anecdotes are brought up, which captured interesting circumstances in that evolutionary phase of the amp; 64257;eld. Be cause the focus was on historical perspectives rather than a comprehensive review of the amp; 64257;eld, recent develop ments intentionally were not addresse

Septin 9 isoform expression, localization and epigenetic changes during human and mouse breast cancer progression

International audienceABSTRACT: INTRODUCTION: Altered expression of Septin 9 (SEPT9), a septin coding for multiple isoform variants, has been observed in several carcinomas including colorectal, head and neck, ovarian and breast, compared to normal tissue. Mechanisms regulating its expression during tumor initiation and progression in vivo and the oncogenic function of its different isoforms remain elusive. METHODS: Using an integrative approach, we investigated SEPT9 at the genetic, epigenetic, mRNA, and protein levels in breast cancer. We analyzed a panel of breast cancer cell lines, human primary tumors and corresponding tumor-free areas, normal breast from reduction mammoplasty patients, as well as primary mammary gland adenocarcinomas derived from the Polyoma Virus Middle T antigen mouse model (PyMT). MCF7 clones expressing individual GFP-tagged SEPT9 isoforms were used to determine their respective intracellular distribution and affect on cell migration. RESULTS: An overall increase in gene amplification and altered expression of SEPT9 was observed during breast tumorigenesis. We identified an intragenic alternative promoter whose methylation regulates SEPT9_v3 expression. Transfection of specific GFP-SEPT9 isoforms in MCF7 cells indicates that these isoforms exhibit differential localization and affect migration rates. Additionally, the loss of an uncharacterized SEPT9 nucleolar localization is observed during tumorigenesis. CONCLUSIONS: In this study we found conserved in vivo changes of SEPT9 gene amplification and overexpression during human and mouse breast tumorigenesis. We show that DNA methylation is a prominent mechanism responsible for regulating differential SEPT9 isoform expression and that breast tumor samples exhibit distinctive SEPT9 intracellular localization. Together, these findings support the significance of SEPT9 as a promising tool in breast cancer detection and further emphasize the importance of analyzing and targeting SEPT9 isoform specific expression and function

Assay development and high-throughput screening for small molecule inhibitors of a Vibrio cholerae stress response pathway

Laura Stanbery, Jyl S Matson Department of Medical Microbiology and Immunology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, USA Abstract: Antibiotics are important adjuncts to oral rehydration therapy in cholera disease management. However, due to the rapid emergence of resistance to the antibiotics used to treat cholera, therapeutic options are becoming limited. Therefore, there is a critical need to develop additional therapeutics to aid in the treatment of cholera. Previous studies showed that the extracytoplasmic stress response (σE) pathway of Vibrio cholerae is required for full virulence of the organism. The pathway is also required for bacterial growth in the presence of ethanol. Therefore, we exploited this ethanol sensitivity phenotype in order to develop a screen for inhibitors of the pathway, with the aim of also inhibiting virulence of the pathogen. Here we describe the optimization and implementation of our high-throughput screening strategy. From a primary screen of over 100,000 compounds, we have identified seven compounds that validated the growth phenotypes from the primary and counterscreens. These compounds have the potential to be developed into therapeutic agents for cholera and will also be valuable probes for uncovering basic molecular mechanisms of an important cause of diarrheal disease. Keywords: Vibrio cholerae, stress response, σE, high-throughput screenin

CIGS photovoltaics reviewing an evolving paradigm

Copper indium selenide chalcopyrite structure alloys with gallium CIGS are unique among the highest performing photovoltaic PV semiconductor technologies. They are structurally disordered, nonstoichiometric materials that have been engineered to achieve remarkably low bulk nonradiative recombination levels. Nevertheless, their performance can be further improved. This review adopts a fundamental thermodynamic perspective to comparatively assess the root causes of present limitations on CIGS PV performance. The topics of selectivity and passivation of contacts to CIGS and its multinary alloys are covered, highlighting pathways to maximizing the electrochemical potential between those contacts under illumination. An overview of absorber growth methods and resulting properties is also provided. We recommend that CIGS researchers consider strategies that have been successfully implemented in the more mature wafer based GaAs and Si PV device technologies, based on the paradigm of an idealized PV device design using an isotropic absorber with minimal nonradiative recombination, maximal light trapping, and both electron selective and hole selective passivated contacts. We foresee that CIGS technology will reach the 25 efficiency level within the next few years through enhanced collection and reduced recombination. To significantly impact power generation applications, cost effective, manufacturable solutions are also essentia

On the Rocks: Quantifying Storage of Inorganic Soil Carbon on Gravels and Determining Pedon-Scale Variability

The storage and flux of carbon from soils, the planet\u27s third largest carbon pool, strongly influence the global carbon cycle and are essential, but poorly constrained, parameters for global climate models. An estimated 40% of all soil carbon is stored as inorganic carbonate minerals. Despite a recognition of the importance of soil inorganic carbon (SIC) in soil carbon storage, few studies have quantified pedon-scale variability in SIC storage. We examine different stages of carbonate development and accumulation rates between gravelly and non-gravelly soils. Studies often ignore carbonate coatings on gravels in measurements of soil inorganic carbon (SIC). By quantifying and differentiating the fine (\u3c 2 mm) and coarse (\u3e 2 mm) fractions of SIC in the Reynolds Creek Experimental Watershed in southwestern Idaho, we show that gravel coatings contain up to 44% of total SIC at a given site. Among the 26 soil sites examined throughout the watershed, an average of 13% of the total SIC is stored as carbonate coatings within in the gravel fraction. We measured a high level of pedon-scale field variability (up to 220%) among the three sampled faces of 1 m3 soil pits. Analytical error associated with the modified pressure calcimeter (0.001–0.014%) is considerably less than naturally occurring heterogeneities in SIC within the soil profile. This work highlights and quantifies two sources of uncertainty in studies of SIC needed to inform future research. First, in gravelly sites, the \u3e 2 mm portion of soils may store a large percentage of SIC. Second, SIC varies considerably at the pedon-scale, so studies attempting to quantify carbon storage over landscape scales need to consider this variability

Silicon nitride anti-reflection coatings for CdS/CuInSe2 thin film solar cells by electron beam assisted chemical vapor deposition

Includes bibliographical references (page 291).The electron beam assisted chemical vapor deposition of silicon nitride anti-reflection coatings onto thin film CdS/CuInSe2 solar cells and the resultant effects on their performance are reported. In some cases large increases in the short circuit current, open circuit voltage and fill factor were observed. The present results are explained by the usual index matching anti-reflection mechanisms and either the passivation of undesirable shunts or improvement of intrinsic diode characteristics

Different selective pressures lead to different genomic outcomes as newly-formed hybrid yeasts evolve

Abstract Background Interspecific hybridization occurs in every eukaryotic kingdom. While hybrid progeny are frequently at a selective disadvantage, in some instances their increased genome size and complexity may result in greater stress resistance than their ancestors, which can be adaptively advantageous at the edges of their ancestors' ranges. While this phenomenon has been repeatedly documented in the field, the response of hybrid populations to long-term selection has not often been explored in the lab. To fill this knowledge gap we crossed the two most distantly related members of the Saccharomyces sensu stricto group, S. cerevisiae and S. uvarum, and established a mixed population of homoploid and aneuploid hybrids to study how different types of selection impact hybrid genome structure. Results As temperature was raised incrementally from 31°C to 46.5°C over 500 generations of continuous culture, selection favored loss of the S. uvarum genome, although the kinetics of genome loss differed among independent replicates. Temperature-selected isolates exhibited greater inherent and induced thermal tolerance than parental species and founding hybrids, and also exhibited ethanol resistance. In contrast, as exogenous ethanol was increased from 0% to 14% over 500 generations of continuous culture, selection favored euploid S. cerevisiae x S. uvarum hybrids. Ethanol-selected isolates were more ethanol tolerant than S. uvarum and one of the founding hybrids, but did not exhibit resistance to temperature stress. Relative to parental and founding hybrids, temperature-selected strains showed heritable differences in cell wall structure in the forms of increased resistance to zymolyase digestion and Micafungin, which targets cell wall biosynthesis. Conclusions This is the first study to show experimentally that the genomic fate of newly-formed interspecific hybrids depends on the type of selection they encounter during the course of evolution, underscoring the importance of the ecological theatre in determining the outcome of the evolutionary play.</p

Clonal Neoantigen: Emerging “Mechanism-based” Biomarker of Immunotherapy Response

Clonal mutations represent the initiating molecular defects related to cellular transition of a normal phenotype to a malignant phenotype. Molecular genomic assessment utilizing next generation and whole exome sequencing is now being increasingly applied to biomarker determination to refine the use of targeted immune therapies. Case examples followed by retrospective study assessment have convincingly demonstrated clonal neoantigens provide a relevant predictor of response to checkpoint inhibition. A meta-analysis, by Litchfield et al., of over 1000 cancer patients from 12 landmark trials demonstrated no clinical benefit to checkpoint inhibitor (CPI) therapy in correlation to high subclonal tumor mutational burden (TMB), whereas high clonal TMB was found to be significantly correlated with better overall survival (p = 0.000000029). We discuss the mechanism of clonal vs. subclonal neoantigen targeting relationship to homologous recombination proficient (HRP) profile, evidence of preclinical and clinical benefit related to clonal neoantigens, and review a novel developing therapy called Vigil®, designed to expand the clonal neoantigen targeting effector cell populations. Vigil® is an autologous cellular immunotherapy which is designed to carry the full set of personal clonal neoantigens. Phase 2b results demonstrate a durable recurrence-free survival (RFS) and overall survival (OS) advantage for Vigil® in a subset ovarian cancer population with an HRP cancer profile

Maternal IgG and IgA Antibodies Dampen Mucosal T Helper Cell Responses in Early Life

To maintain a symbiotic relationship between the host and its resident intestinal microbiota, appropriate mucosal T&nbsp;cell responses to commensal antigens must be established. Mice acquire both IgG and IgA maternally; the former has primarily been implicated in passive immunity to pathogens while the latter mediates host-commensal mutualism. Here, we report the surprising observation that mice generate T&nbsp;cell-independent and largely Toll-like receptor (TLR)-dependent IgG2b and IgG3 antibody responses against their gut microbiota. We demonstrate that maternal acquisition of these antibodies dampens mucosal T follicular helper responses and subsequent germinal center B cell responses following birth. This work reveals a feedback loop whereby T&nbsp;cell-independent, TLR-dependent antibodies limit mucosal adaptive immune responses to newly acquired commensal antigens and uncovers a broader function for maternal IgG