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Abstract Altered gut microbiota (GM) potentially contribute to development or worsening of sarcopenia through a gut‐muscle axis. This systematic review aims to compare GM between persons with sarcopenia or low sarcopenia‐defining parameters (muscle mass, strength, and physical performance) to those with preserved muscle status, as well as to clarify possible associations between sarcopenia (‐defining parameters) and relative abundance (RA) of GM‐taxa or GM‐(α‐ or β) diversity indices, in order to clarify whether there is robust evidence of the existence of a GM signature for sarcopenia. This systematic review was conducted according to the PRISMA‐reporting guideline and pre‐registered on PROSPERO (CRD42021259597). PubMed, Web of Science, Embase, ClinicalTrials.gov, and Cochrane library were searched until 20 July 2023. Included studies reported on GM and sarcopenia or its defining parameters. Observational studies were included with populations of mean age ≥50 years. Thirty‐two studies totalling 10 781 persons (58.56% ♀) were included. Thirteen studies defined sarcopenia as a construct. Nineteen studies reported at least one sarcopenia‐defining parameter (muscle mass, strength or physical performance). Studies found different GM‐taxa at multiple levels to be significantly associated with sarcopenia (n = 4/6), muscle mass (n = 13/14), strength (n = 7/9), and physical performance (n = 3/3); however, directions of associations were heterogeneous and also conflicting for specific GM‐taxa. Regarding β‐diversity, studies found GM of persons with sarcopenia, low muscle mass, or low strength to cluster differently compared with persons with preserved muscle status. α‐diversity was low in persons with sarcopenia or low muscle mass as compared with those with preserved muscle status, indicating low richness and diversity. In line with this, α‐diversity was significantly and positively associated with muscle mass (n = 3/4) and muscle strength (n = 2/3). All reported results were significant (P

The Pyrenean Platform for Observation of the Atmosphere (P2OA) is a coupled plain–mountain instrumented platform in southwestern France. It is composed of two physical sites: the “Pic du Midi” mountaintop observatory (2877 m a.s.l.) and the “Centre de Recherches Atmosphériques” (600 m a.s.l). Both sites are complementarily instrumented for the monitoring of climate-relevant variables and the study of meteorological processes in a mountainous region. The scientific topics covered by P2OA include surface–atmosphere interactions in heterogeneous landscapes and complex terrain, the physics and chemistry of atmospheric trace species at a large scale, the influence of local- and regional-scale emissions and transport on the atmospheric composition, and transient luminous events above thunderstorms. With a large number of instruments and a high hosting capacity, P2OA contributes to atmospheric sciences through (i) building long-term series of atmospheric observations, (ii) hosting experimental field campaigns and instrumental tests, and (iii) educational training in atmospheric observation techniques. In this context, P2OA is part of the French component of the Aerosol, Clouds and Trace Gases Research Infrastructure (ACTRIS-Fr) and also contributes to the Integrated Carbon Observation System (ICOS) research infrastructure and to several European or international networks. Here, we present the complete instrumentation of P2OA and the associated datasets, give a meteorological characterization of the platform, and illustrate the potential of P2OA and its dataset with past or ongoing studies and projects.

Abstract Dedifferentiated liposarcoma (DDLPS) is the most frequent high-grade soft tissue sarcoma subtype. It is characterized by a component of undifferentiated tumor cells coexisting with a component of well-differentiated adipocytic tumor cells. Both dedifferentiated (DD) and well-differentiated (WD) components exhibit MDM2 amplification, however their cellular origin remains elusive. Using single-cell RNA sequencing, DNA sequencing, in situ multiplex immunofluorescence and functional assays in paired WD and DD components from primary DDLPS tumors, we characterize the cellular heterogeneity of DDLPS tumor and micro-environment. We identify a population of tumor adipocyte stem cells (ASC) showing striking similarities with adipocyte stromal progenitors found in white adipose tissue. We show that tumor ASC harbor the ancestral genomic alterations of WD and DD components, suggesting that both derive from these progenitors following clonal evolution. Last, we show that DD tumor cells keep important biological properties of ASC including pluripotency and that their adipogenic properties are inhibited by a TGF-β-high immunosuppressive tumor micro-environment.

Abstract In multiple myeloma, as in B‐cell malignancies, mono‐ and especially bi‐allelic TP53 gene inactivation is a high‐risk factor for treatment resistance, and there are currently no therapies specifically targeting p53 deficiency. In this study, we evaluated if the loss of cell cycle control in p53‐deficient myeloma cells would confer a metabolically actionable vulnerability. We show that CTP synthase 1 (CTPS1), which encodes a CTP synthesis rate‐limiting enzyme essential for DNA and RNA synthesis in lymphoid cells, is overexpressed in samples from myeloma patients displaying a high proliferation rate (high MKI67 expression) or a low p53 score (synonymous with TP53 deletion and/or mutation). This overexpression of CTPS1 was associated with reduced survival in two cohorts. Using scRNA‐seq analysis in 24 patient samples, we further demonstrate that myeloma cells in the S or G2/M phase display high CTPS1 expression. Pharmacological inhibition of CTPS1 by STP‐B induced cell cycle arrest in early S phase in isogenic NCI‐H929 or XG7 TP53+/+, TP53−/−, and TP53R175H/R175H cells and in a TP53−/R123STOP patient sample. The functional annotation of transcriptional changes in 10 STP‐B‐treated myeloma cell lines revealed a decrease in protein translation and confirmed the blockade of cells into the S phase. The pharmacological inhibition of ATR, which governs the intrinsic S/G2 checkpoint, in STP‐B‐induced S‐phase arrested cells synergistically induced cell death in TP53+/+, TP53−/−, and TP53R175H/R175H isogenic cell lines (Bliss score >15). This combination induced replicative stress and caspase‐mediated cell death and was highly effective in resistant/refractory patient samples with TP53 deletion and/or mutation and in TP53−/− NCI‐H929 xenografted NOD‐scid IL2Rgamma mice. Our in vitro, ex vivo, and in vivo data provide the rationale for combined CTPS1 and ATR inhibition for the treatment of p53‐deficient patients.

The gut microbiome is important for human health, yet modulation requires more insight into inter-individual variation. Here, we explored latent structures of the human gut microbiome across the human lifespan, applying partitioning, pseudotime, and ordination approaches to >35,000 samples. Specifically, three major gut microbiome branches were identified, within which multiple partitions were observed in adulthood, with differential abundances of species along branches. Different compositions and metabolic functions characterized the branches' tips, reflecting ecological differences. An unsupervised network analysis from longitudinal data from 745 individuals showed that partitions exhibited connected gut microbiome states rather than over-partitioning. Stability in the Bacteroides-enriched branch was associated with specific ratios of Faecalibacterium:Bacteroides. We also showed that associations with factors (intrinsic and extrinsic) could be generic, branch- or partition-specific. Our ecological framework for cross-sectional and longitudinal data allows a better understanding of overall variation in the human gut microbiome and disentangles factors associated with specific configurations.

Abstract Free charge generation after photoexcitation of donor or acceptor molecules in organic solar cells generally proceeds via (1) formation of charge transfer states and (2) their dissociation into charge separated states. Research often either focuses on the first component or the combined effect of both processes. Here, we provide evidence that charge transfer state dissociation rather than formation presents a major bottleneck for free charge generation in fullerene-based blends with low energetic offsets between singlet and charge transfer states. We investigate devices based on dilute donor content blends of (fluorinated) ZnPc:C60 and perform density functional theory calculations, device characterization, transient absorption spectroscopy and time-resolved electron paramagnetic resonance measurements. We draw a comprehensive picture of how energies and transitions between singlet, charge transfer, and charge separated states change upon ZnPc fluorination. We find that a significant reduction in photocurrent can be attributed to increasingly inefficient charge transfer state dissociation. With this, our work highlights potential reasons why low offset fullerene systems do not show the high performance of non-fullerene acceptors.

Organisms release and detect molecules for defense, reproduction, feeding strategies and finding suitable habitats. For some migratory species, homing behavior could be related to the recognition of their home chemical fingerprint made of an assemblage of molecules from their habitat. In the marine realm, the functioning of ecosystems such as underwater caves largely depends on trophic interactions between the caves and the outside environment. A key feature of these interactions relies on the circadian migration of small crustaceans (Mysida) from the cave habitat to the open sea. Recently, it has been hypothesized that these migrations could involve chemical mediation. Behavioral experiments using a two-choice system have shown that cave mysids significantly detect cave seawater rather than a control water from the open sea. Here, we used the same experimental system to investigate habitat recognition by two populations of the cave mysid Hemimysis margalefi. Both populations were submitted to a choice between three distinct cave seawaters vs. a control seawater. Additionally, experiments tested the water preference of a non-cave mysid species (Leptomysis sp.) between control and cave seawaters. To evaluate whether the choice of mysids was influenced by chemical cues from conspecifics, a complementary experiment on H. margalefi was conducted. Results demonstrated that each studied mysids population significantly recognizes the water of its own home habitat, and that this behavior is not influenced by the occurrence of H. margalefi’s exudates. Mass spectrometry-based metabolomic analyses revealed that each cave seawater had a specific chemical fingerprint with only a few reproducibly detected signals belonging to different chemical classes: peptides, alkaloids, fatty acids, steroids but also inorganic molecules. Organic pollutants have also been reproducibly detected. Among the detected compounds, one oxylipin derivative and one peptide could be considered as chemical markers of the cave ecosystem. Therefore, we postulate that the chemical seascape of each cave participates to mysid circadian migrations which are analogous to a daily-based homing behavior.

Many studies have identified an association between exposure to the natural environment and improved public-health outcomes. However, much of this observational work lacks a theoretical foundation, so we look to the humanities for a stronger basis for green-health research, examining how trees have been used as religious metaphors and symbols for health and wellbeing. In particular, the tree of life, sacred trees, and other religious symbols provide a promising theoretical basis for green-health research. Based on this review, we propose the value of incorporating attributes such as vegetation species and size in exposure metrics, and considering the interactions between exposure attributes (e.g., species) and individual attributes (e.g., culture).

Long time series of observations of atmospheric dynamics and composition are collected at the French Pyrenean Platform for Observation of the Atmosphere (P2OA). Planetary boundary layer depth is a key variable of the climate system, but it remains difficult to estimate and analyse statistically. In order to obtain reliable estimates of the convective boundary layer height (Zi) and to allow long-term series analyses, a new restitution algorithm, named CALOTRITON, has been developed. It is based on the observations of an ultra-high-frequency (UHF) radar wind profiler (RWP) from P2OA with the help of other instruments for evaluation. Estimates of Zi are based on the principle that the top of the convective boundary layer is associated with both a marked inversion and a decrease in turbulence. Those two criteria are respectively manifested by larger RWP reflectivity and smaller vertical-velocity Doppler spectral width. With this in mind, we introduce a new UHF-deduced dimensionless parameter which weighs the air refractive index structure coefficient with the inverse of vertical velocity standard deviation to the power of x. We then search for the most appropriate local maxima of this parameter for Zi estimates with defined criteria and constraints such as temporal continuity. Given that Zi should correspond to fair-weather cloud base height, we use ceilometer data to optimize our choice of the power x and find that x=3 provides the best comparisons. The estimates of Zi by CALOTRITON are evaluated using different Zi estimates deduced from radiosounding according to different definitions. The comparison shows excellent results with a regression coefficient of up to 0.96 and a root-mean-square error of 71 m, which is close to the vertical resolution of the UHF RWP of 75 m, when conditions are optimal. In more complex situations, that is when the atmospheric vertical structure is itself particularly ambiguous, secondary retrievals allow us to identify potential thermal internal boundary layers or residual layers and help to qualify the Zi estimations. Frequent estimate errors are observed nevertheless; for example, when Zi is below the UHF RWP first reliable gate or when the boundary layer begins its transition to a stable nocturnal boundary layer.

Abstract Nonlinear optical response of solid-state materials exposed to strong non-resonant light fields leads to the generation of harmonic frequencies as a consequence of interband polarization and coherent intraband dynamics of the electrons. The efficient production of a macroscopic wave requires the preservation of the mutual phase between the driving wave and the individual microscopic sources of radiation. Here, we experimentally and theoretically show that the yield of high harmonic generation in a photodoped silicon crystal is enhanced by the nonlinear intraband current whose amplitude depends not only on the volume density of the photogenerated carriers but also on their momentum distributions within the bands. The strongest enhancement is reached when the carrier system is relaxed to the band minima before interacting with the strong nonresonant wave, which drives the high harmonic generation. These results extend the possibilities of high harmonic spectroscopy towards the investigation of ultrafast carrier relaxation in condensed matter.

Abstract Outdoor recreation is an essential way many people engage with nature. The provision of public spaces for recreation intersects with conservation practices motivated by intertwined social and ecological values, such as strict practices associated with the concept of ‘wilderness’. Debates persist about how such concepts and management practices influence people's recreation experiences. Many US public land management agencies facilitate opportunities for outdoor recreation, relying on management frameworks and tools intended to foster specific experiential qualities. But these frameworks and tools assume simplistic relationships between settings and people's experiences, and managers rarely assess these relationships. This study uses a data set of nearly 70,000 crowdsourced trip reports from a hiking website to understand the qualities of visitors' experiences on trails. We study the geographic distribution of experiential qualities commonly associated with US wilderness areas: aesthetics, awe, challenge, pristineness, quietness, solitude and timelessness. Using analytical methods that rely on machine learning and natural language processing, we identify these experiential qualities in trip reports from hundreds of routes, and use generalized linear models to analyse relationships between the frequency of each experiential quality and the route's administrative, built, biophysical, geographic and social settings. We find that four of the seven experiential qualities (aesthetics, awe, challenge and solitude) are commonly described in trip reports, each appearing in 15%–55% of manually coded reports. The extent to which setting characteristics explained variability in experiences differed, ranging from 34% of the variability in the proportion of trip reports describing aesthetics to 55% for awe. The setting characteristics associated with each experiential quality also differed, with characteristics such as trail mileage and summit destinations having stronger influences on experiential qualities than characteristics such as wilderness designation. Synthesis and applications. Our findings suggest the need to consider more diverse variables in experience–setting relationships, develop more robust models to characterize those relationships and create new data sources to represent understudied variables. These advances would help empirically inform and improve frameworks and tools used for recreation and wilderness planning and monitoring, and potentially promote more responsive management to evolving social–ecological values. Read the free Plain Language Summary for this article on the Journal blog.

At high-altitude stations worldwide, atmospheric composition measurements aim to represent the free troposphere and intercontinental scale. The high-altitude environment favours local and regional air mass transport, impacting the sampled air composition. Processes like mixing, source–receptor pathways, and chemistry rely on local and regional weather patterns, necessitating station-specific characterization. The Pic du Midi (PDM) is a mountaintop observatory at 2850 m above sea level in the Pyrenees. The PDM and the Centre de Recherches Atmosphériques (CRA) in the foothills form the Pyrenean Platform for the Observation of the Atmosphere (P2OA). This study aimed to identify recurring weather patterns at P2OA and relate them to the PDM's atmospheric composition. We combined 5 years of data from PDM and CRA, including 23 meteorological variables (temperature, humidity, cloud cover, and wind at different altitudes). We used hierarchical clustering to classify the data set into six clusters. Three of the clusters represented common weather conditions (fair, mixed, disturbed weather), one highlighted winter north-westerly windstorms, and the last two denoted south foehn conditions. Additional diagnostic tools allowed us to study specific phenomena such as foehns and thermally driven circulations and to affirm our understanding of the clusters. We then analysed the PDM's atmospheric composition statistics for each cluster. Notably, radon measurements indicated a regional background dominance in the lower troposphere, overshadowing diurnal thermal effects. Cluster differences emerged for the anomalies in CO, CO2, CH4, O3, and aerosol concentrations, and we propose interpretations in relation to chemical sources and sinks.

Abstract Fungi are integral to well-functioning ecosystems, and their broader impact on Earth systems is widely acknowledged. Fossil evidence from the Rhynie Chert (Scotland, UK) shows that Fungi were already diverse in terrestrial ecosystems over 407-million-years-ago, yet evidence for the occurrence of Dikarya (the subkingdom of Fungi that includes the phyla Ascomycota and Basidiomycota) in this site is scant. Here we describe a particularly well-preserved asexual fungus from the Rhynie Chert which we examined using brightfield and confocal microscopy. We document Potteromyces asteroxylicola gen. et sp. nov. that we attribute to Ascomycota incertae sedis (Dikarya). The fungus forms a stroma-like structure with conidiophores arising in tufts outside the cuticle on aerial axes and leaf-like appendages of the lycopsid plant Asteroxylon mackiei. It causes a reaction in the plant that gives rise to dome-shaped surface projections. This suite of features in the fungus together with the plant reaction tissues provides evidence of it being a plant pathogenic fungus. The fungus evidently belongs to an extinct lineage of ascomycetes that could serve as a minimum node age calibration point for the Ascomycota as a whole, or even the Dikarya crown group, along with some other Ascomycota previously documented in the Rhynie Chert.

Domestic dogs (Canis lupus familiaris) are the most variable-sized mammalian species on Earth, displaying a 40-fold size difference between breeds.1 Although dogs of variable size are found in the archeological record,2-4 the most dramatic shifts in body size are the result of selection over the last two centuries, as dog breeders selected and propagated phenotypic extremes within closed breeding populations.5 Analyses of over 200 domestic breeds have identified approximately 20 body size genes regulating insulin processing, fatty acid metabolism, TGFβ signaling, and skeletal formation.6-10 Of these, insulin-like growth factor 1 (IGF1) predominates, controlling approximately 15% of body size variation between breeds.8 The identification of a functional mutation associated with IGF1 has thus far proven elusive.6,10,11 Here, to identify and elucidate the role of an ancestral IGF1 allele in the propagation of modern canids, we analyzed 1,431 genome sequences from 13 species, including both ancient and modern canids, thus allowing us to define the evolutionary history of both ancestral and derived alleles at this locus. We identified a single variant in an antisense long non-coding RNA (IGF1-AS) that interacts with the IGF1 gene, creating a duplex. While the derived mutation predominates in both modern gray wolves and large domestic breeds, the ancestral allele, which predisposes to small size, was common in small-sized breeds and smaller wild canids. Our analyses demonstrate that this major regulator of canid body size nearly vanished in Pleistocene wolves, before its recent resurgence resulting from human-imposed selection for small-sized breed dogs.

BackgroundIndividual diet components and specific dietary regimens have been shown to impact the gut microbiome.ObjectivesHere, we explored the contribution of long-term diet by searching for dietary patterns that would best associate with the gut microbiome in a population-based cohort.MethodsUsing a priori and a posteriori approaches, we constructed dietary patterns from an FFQ completed by 1800 adults in the American Gut Project. Dietary patterns were defined as groups of participants or combinations of food variables (factors) driven by criteria ranging from individual nutrients to overall diet. We associated these patterns with 16S ribosomal RNA-based gut microbiome data for a subset of 744 participants.ResultsCompared to individual features (e.g., fiber and protein), or to factors representing a reduced number of dietary features, 5 a posteriori dietary patterns based on food groups were best associated with gut microbiome beta diversity (P ≤ 0.0002). Two patterns followed Prudent-like diets-Plant-Based and Flexitarian-and exhibited the highest Healthy Eating Index 2010 (HEI-2010) scores. Two other patterns presented Western-like diets with a gradient in HEI-2010 scores. A fifth pattern consisted mostly of participants following an Exclusion diet (e.g., low carbohydrate). Notably, gut microbiome alpha diversity was significantly lower in the most Western pattern compared to the Flexitarian pattern (P ≤ 0.009), and the Exclusion diet pattern was associated with low relative abundance of Bifidobacterium (P ≤ 1.2 × 10-7), which was better explained by diet than health status.ConclusionsWe demonstrated that global-diet a posteriori patterns were more associated with gut microbiome variations than individual dietary features among adults in the United States. These results confirm that evaluating diet as a whole is important when studying the gut microbiome. It will also facilitate the design of more personalized dietary strategies in general populations.