A Family of Secretory Proteins Is Associated with Different Morphotypes in Cryptococcus neoformans

Cryptococcus neoformans, an opportunistic human fungal pathogen, can undergo a yeast-to-hypha transition in response to environmental cues. This morphological transition is associated with changes in the expression of cell surface proteins. The Cryptococcus cell surface and secreted protein Cfl1 was the first identified adhesin in the Basidiomycota. Cfl1 has been shown to regulate morphology, biofilm formation, and intercellular communication. Four additional homologs of CFL1 are harbored by the Cryptococcus genome: DHA1, DHA2, CPL1, and CFL105. The common features of this gene family are the conserved C-terminal SIGC domain and the presence of an N-terminal signal peptide. We found that all these Cfl1 homolog proteins are indeed secreted extracellularly. Interestingly, some of these secretory proteins display cell type-specific expression patterns: Cfl1 is hypha specific, Dha2 is yeast specific, and Dha1 (delayed hypersensitivity antigen 1) is expressed in all cell types but is particularly enriched at basidia. Interestingly, Dha1 is induced by copper limitation and suppressed by excessive copper in the medium. This study further attests to the physiological heterogeneity of the Cryptococcus mating colony, which is composed of cells with heterogeneous morphotypes. The differential expression of these secretory proteins contributes to heterogeneity, which is beneficial for the fungus to adapt to changing environments. IMPORTANCE Heterogeneity in physiology and morphology is an important bet-hedging strategy for nonmobile microbes such as fungi to adapt to unpredictable environmental changes. Cryptococcus neoformans, a ubiquitous basidiomycetous fungus, is known to switch from the yeast form to the hypha form during sexual development. However, in a mating colony, only a subset of yeast cells switch to hyphae, and only a fraction of the hyphal subpopulation will develop into fruiting bodies, where meiosis and sporulation occur. Here, we investigated a basidiomycete-specific secretory protein family. We found that some of these proteins are cell type specific, thus contributing to the heterogeneity of a mating colony. Our study also demonstrates the importance of examining the protein expression pattern at the individual-cell level in addition to population gene expression profiling for the investigation of a heterogeneous community

The long-term evolution of the atmosphere of Venus: processes and feedback mechanisms

In this chapter, we focus on the long-term evolution of the atmosphere of Venus, and how it has been affected by interior/exterior cycles. The formation and evolution of Venus's atmosphere, leading to the present-day surface conditions, remain hotly debated and involve questions that tie into many disciplines. Here, we explore the mechanisms that shaped the evolution of the atmosphere, starting with the volatile sources and sinks. Going from the deep interior to the top of the atmosphere, we describe fundamental processes such as volcanic outgassing, surface-atmosphere interactions, and atmosphere escape. Furthermore, we address more complex aspects of the history of Venus, including the role of meteoritic impacts, how magnetic field generation is tied into long-term evolution, and the implications of feedback cycles for atmospheric evolution. Finally, we highlight three plausible end-member evolutionary pathways that Venus might have followed, from the accretion to its present-day state, based on current modeling and observations. In a first scenario, the planet was desiccated early-on, during the magma ocean phase, by atmospheric escape. In a second scenario, Venus could have harbored surface liquid water for long periods of time, until its temperate climate was destabilized and it entered a runaway greenhouse phase. In a third scenario, Venus's inefficient outgassing could have kept water inside the planet, where hydrogen was trapped in the core and the mantle was oxidized. We discuss existing evidence and future observations/missions needed to refine our understanding of the planet's history and of the complex feedback cycles between the interior, surface, and atmosphere that operate in the past, present or future of Venus

The Long-Term Evolution of the Atmosphere of Venus: Processes and Feedback Mechanisms: Interior-Exterior Exchanges

This work reviews the long-term evolution of the atmosphere of Venus, and modulation of its composition by interior/exterior cycling. The formation and evolution of Venus’s atmosphere, leading to contemporary surface conditions, remain hotly debated topics, and involve questions that tie into many disciplines. We explore these various inter-related mechanisms which shaped the evolution of the atmosphere, starting with the volatile sources and sinks. Going from the deep interior to the top of the atmosphere, we describe volcanic outgassing, surface-atmosphere interactions, and atmosphere escape. Furthermore, we address more complex aspects of the history of Venus, including the role of Late Accretion impacts, how magnetic field generation is tied into long-term evolution, and the implications of geochemical and geodynamical feedback cycles for atmospheric evolution. We highlight plausible end-member evolutionary pathways that Venus could have followed, from accretion to its present-day state, based on modeling and observations. In a first scenario, the planet was desiccated by atmospheric escape during the magma ocean phase. In a second scenario, Venus could have harbored surface liquid water for long periods of time, until its temperate climate was destabilized and it entered a runaway greenhouse phase. In a third scenario, Venus’s inefficient outgassing could have kept water inside the planet, where hydrogen was trapped in the core and the mantle was oxidized. We discuss existing evidence and future observations/missions required to refine our understanding of the planet’s history and of the complex feedback cycles between the interior, surface, and atmosphere that have been operating in the past, present or future of Venus

Machine Learning Detects Pan-cancer Ras Pathway Activation in The Cancer Genome Atlas.

Precision oncology uses genomic evidence to match patients with treatment but often fails to identify all patients who may respond. The transcriptome of these "hidden responders" may reveal responsive molecular states. We describe and evaluate a machine-learning approach to classify aberrant pathway activity in tumors, which may aid in hidden responder identification. The algorithm integrates RNA-seq, copy number, and mutations from 33 different cancer types across The Cancer Genome Atlas (TCGA) PanCanAtlas project to predict aberrant molecular states in tumors. Applied to the Ras pathway, the method detects Ras activation across cancer types and identifies phenocopying variants. The model, trained on human tumors, can predict response to MEK inhibitors in wild-type Ras cell lines. We also present data that suggest that multiple hits in the Ras pathway confer increased Ras activity. The transcriptome is underused in precision oncology and, combined with machine learning, can aid in the identification of hidden responders

A roadmap to the efficient and robust characterization of temperate terrestrial planet atmospheres with JWST

Ultra-cool dwarf stars are abundant, long-lived, and uniquely suited to enable the atmospheric study of transiting terrestrial companions with JWST. Amongst them, the most prominent is the M8.5V star TRAPPIST-1 and its seven planets, which have been the favored targets of eight JWST Cycle 1 programs. While Cycle 1 observations have started to yield preliminary insights into the planets, they have also revealed that their atmospheric exploration requires a better understanding of their host star. Here, we propose a roadmap to characterize the TRAPPIST-1 system -- and others like it -- in an efficient and robust manner. We notably recommend that -- although more challenging to schedule -- multi-transit windows be prioritized to constrain stellar heterogeneities and gather up to 2$\times$ more transits per JWST hour spent. We conclude that in such systems planets cannot be studied in isolation by small programs, thus large-scale community-supported programs should be supported to enable the efficient and robust exploration of terrestrial exoplanets in the JWST era

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km² resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e., offset) between in-situ soil temperature measurements, based on time series from over 1200 1-km² pixels (summarized from 8500 unique temperature sensors) across all the world’s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in-situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world\u27s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications