Evolutionary Advantage Conferred by an Eukaryote-to-Eukaryote Gene Transfer Event in Wine Yeasts

Although an increasing number of horizontal gene transfers have been reported in eukaryotes, experimental evidence for their adaptive value is lacking. Here, we report the recent transfer of a 158-kb genomic region between Torulaspora microellipsoides and Saccharomyces cerevisiae wine yeasts or closely related strains. This genomic region has undergone several rearrangements in S. cerevisiae strains, including gene loss and gene conversion between two tandemly duplicated FOT genes encoding oligopeptide transporters. We show that FOT genes confer a strong competitive advantage during grape must fermentation by increasing the number and diversity of oligopeptides that yeast can utilize as a source of nitrogen, thereby improving biomass formation, fermentation efficiency, and cell viability. Thus, the acquisition of FOT genes has favored yeast adaptation to the nitrogen-limited wine fermentation environment. This finding indicates that anthropic environments offer substantial ecological opportunity for evolutionary diversification through gene exchange between distant yeast species

HBsAg-redirected T cells exhibit antiviral activity in HBV-infected human liver chimeric mice

[Background]: Chronic hepatitis B virus (HBV) infection remains incurable. Although HBsAg-specific chimeric antigen receptor (HBsAg-CAR) T cells have been generated, they have not been tested in animal models with authentic HBV infection.[Methods]: We generated a novel CAR targeting HBsAg and evaluated its ability to recognize HBV+ cell lines and HBsAg particles in vitro. In vivo, we tested whether human HBsAg-CAR T cells would have efficacy against HBV-infected hepatocytes in human liver chimeric mice.[Results]: HBsAg-CAR T cells recognized HBV-positive cell lines and HBsAg particles in vitro as judged by cytokine production. However, HBsAg-CAR T cells did not kill HBV-positive cell lines in cytotoxicity assays. Adoptive transfer of HBsAg-CAR T cells into HBV-infected humanized mice resulted in accumulation within the liver and a significant decrease in plasma HBsAg and HBV-DNA levels compared with control mice. Notably, the fraction of HBV core–positive hepatocytes among total human hepatocytes was greatly reduced after HBsAg-CAR T cell treatment, pointing to noncytopathic viral clearance. In agreement, changes in surrogate human plasma albumin levels were not significantly different between treatment and control groups.[Conclusions]: HBsAg-CAR T cells have anti-HBV activity in an authentic preclinical HBV infection model. Our results warrant further preclinical exploration of HBsAg-CAR T cells as immunotherapy for HBV.This work was supported by the National Institutes of Heath grants R01AI094409, R01HL134510, T32DK060445 and 5T32HL092332; the Texas Hepatocellular Carcinoma Consortium (CPRIT RP150587); and the Diana Helis Henry and Adrienne Helis Malvin Medical Research Foundations. The Dan L. Duncan Cancer Center is supported by P30-CA125123. The Integrated Microscopy Core at the Texas Medical Center Digestive Disease Center is supported by P30-DK56338.Peer reviewe

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Curtmetratge. Comunicació Audiovisual. AB61 Realització audiovisual. Curs acadèmic 2008/2009

A new insight into monsoon intraseasonal variability as revealed from distinct wind-precipitation regimes over the southwest coast of India

International audienceThis study evaluates the observed non-linearity in the wind-precipitation relationship over India's southwest coast and maps this non-linearity to monsoon intraseasonal oscillations. The wind-precipitation data is subjected to clustering, and five distinct regimes are identified. The large-scale dynamical and thermodynamical condition that leads to wind-precipitation clustering is explored. It uses novel observations from the Stratosphere-Troposphere wind profiler radar placed over Cochin (10.04° N; 76.33° E) for the period 2019-2021 to derive characteristics of monsoon low-level jets. Out of five wind-precipitation clusters, low wind low precipitation (LWLP) and low wind high precipitation clusters (LWHP) bear signatures of monsoon break conditions over central India. The occurrence of Madden Julian events or monsoon lows in LWHP generates heavy rainfall over the southwest coast. The high wind low precipitation (HWLP) cluster occurs during the weak phase of northward propagating monsoon intraseasonal oscillation (MISO) over the southwest coast, while the high wind high precipitation (HWHP) cluster lies within the strong phase of MISO. The fifth cluster, the high wind extreme precipitation cluster (HWEP), although technically lying within the strong phase of MISO, however has more apparent signatures of northwestward propagating monsoon depressions. The Lagrangian trajectories launched from 500 hPa level for each cluster reveal some intriguing aspects. The dry air intrusion from adjacent regions near the west coast makes the mid-troposphere dry over the southwest coast in LWLP and HWLP clusters. In HWHP and HWEP, strong moisture sources confined over the west coast create mid-troposphere moistening owing to the moisture supply from below 500 hPa. This study highlights that wind-precipitation clustering effectively defines sub-seasonal variability during the monsoon

Correction: A new insight into monsoon intraseasonal variability as revealed from distinct wind-precipitation regimes over the southwest coast of India

International audienc

A Novel approach to evaluate the benefits of casing treatment in axial compressors

International audiencePassive control devices based on casing treatments have already shown their capability to improve the flow stability in axial compressors. However, their optimization remains complex due to a partial understanding of the related physical mechanisms. In order to quantitatively assess the interaction between slots and the blade tip flow, the present paper develops a novel analysis methodology based on a control-volume approach located in the rotor tip region. This methodology may be used for analyzing the casing treatment based on both axi- and non-axisymmetric slots design. The second issue of the paper focuses on the application of the current approach to better understand the effects of axi- and non-axisymmetric grooves in three different axial compressors which differ by the flow regime (subsonic/transonic) and the smooth casing shape (cylindrical/concave). Numerical simulations are performed, and results of the current approach with and without casing treatments are compared

EGFR-Mutant Non-Small-Cell Lung Cancer at Surgical Stages: What Is the Place for Tyrosine Kinase Inhibitors?

The ADAURA trial has been significant for the perception of EGFR tyrosine kinase inhibitors (TKIs) as a tool for early stage non-small-cell lung cancer (NSCLC). It produced such great insight that the main TKI, Osimertinib, was rapidly integrated into international guidelines for adjuvant use. However, EGFR-mutant NSCLC is a complex entity and has various targeting drugs, and the benefits for patients might not be as clear as they seem. We reviewed trials and meta-analyses considering TKI adjuvant and neoadjuvant use. We also explored the influence of mutation variability and financial evaluations. We found that TKIs often show disease-free survival (DFS) benefits, yet studies have struggled to improve the overall survival (OS); however, the results from the literature might be confusing because of variability in the stages and mutations. The safety profiles and adverse events are acceptable, but costs remain high and accessibility might not be optimal. TKIs are promising drugs that could allow for tailored treatment designs

Ordered polyelectrolyte multilayers. Rules governing layering in organic binary multilayers.

We study the growth and internal structure of polyelectrolyte multilayers obtained by combining three polyanions with nine polycations of the ionene family, of systematically varied chemical architecture. We find that, contrary to a generally held belief, ordered organic multilayers are by no way exceptional, provided one of the polyelectrolytes bears groups which induce structure in water, such as long hydrophobic segments or mesogenic groups. However, this condition is not sufficient, as order will or will not emerge in the multilayer depending on the specific pairing of the polyelectrolytes. The results support the notion that layering in the multilayer results from some degree of prestructuring of a water-swollen layer adsorbed during each step of deposition. These findings pave the way to new possible uses of polyelectrolyte multilayers, for example, for applications requiring preferential alignment or strong confinement of specific functional groups