bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-27 maintains cytotoxic Ly6C+γδ T cells that arise from immature precursors
Authors: Wiesheu Robert , Edwards Sarah C. , Hedley Ann , Tosolini Marie , Fares da Silva Marcelo Gregorio Filho , Sumaria Nital , Optaczy Yasmin , Hill David G. , Hayes Alan J. , Hay Jodie , Kilbey Anna , Michie Alison M. , Graham Gerard J. , Manoharan Anand , Halsey Christina , Jones Gareth W. , Blyth Karen , Fournie Jean-Jacques , Pennington Daniel J. , Bekiaris Vasileios , Coffelt Seth B. 
Published: October 2023

ABSTRACTIn mice, γδ T cells that express the co-stimulatory molecule, CD27, are committed to the IFNγ-producing lineage in the thymus, and in the periphery, these cells play a critical role in host defence and anti-tumor immunity. Unlike αβ T cells that rely on MHC-presented peptides to drive their terminal differentiation, it is unclear whether MHC-unrestricted γδ T cells undergo further functional maturation after exiting the thymus. Here, we provide evidence of phenotypic and functional diversity within peripheral IFNγ-producing γδ T cells. We found that immature CD27+Ly6C—cells convert into mature CD27+Ly6C+cells, and these mature cells control cancer progression while the immature cells cannot. The gene signatures of these two subsets were highly analogous to human immature and mature γδ T cells, indicative of conservation across species. We show that IL-27 supports the cytotoxic phenotype and function of mouse CD27+Ly6C+cells and human Vδ2+cells, while IL-27 is dispensable for mouse CD27+Ly6C—cells and human Vδ1+cells. These data reveal increased complexity within IFNγ-producing γδ T cells, comprising of immature and terminally differentiated subsets, that offer new insights into unconventional T cell biology.
Hierarchical Gaussian process models explore the dark meltome of thermal proteome profiling experiments
Authors: Le Sueur Cecile , Rattray Magnus , Savitski Mikhail 
Published: October 2023

AbstractThermal proteome profiling (TPP) is a proteome wide technology that enables unbiased detection of protein drug interactions as well as changes in post-translational state of proteins between different biological conditions. Statistical analysis of temperature range TPP (TPP-TR) datasets relies on comparing protein melting curves, describing the amount of non-denatured proteins as a function of temperature, between different conditions (e.g. presence or absence of a drug). However, state-of-the-art models are restricted to sigmoidal melting behaviours while unconventional melting curves, representing up to 50% of TPP-TR datasets, have recently been shown to carry important biological information.We present a novel statistical framework, based on hierarchical Gaussian process models and named GPMelt, to make TPP-TR datasets analysis unbiased with respect to the melting profiles of proteins. GPMelt scales to multiple conditions, and extension of the model to deeper hierarchies (i.e. with additional sub-levels) allows to deal with complex TPP-TR protocols. Collectively, our statistical framework extends the analysis of TPP-TR datasets for both protein and peptide level melting curves, offering access to thousands of previously excluded melting curves and thus substantially increasing the coverage and the ability of TPP to uncover new biology.Author summaryProteins interactions with other proteins, nucleic acids or metabolites, are key to all biological processes. Being able to detect these interactions is essential to understand biological systems. Thermal proteome profiling is a proteome-wide biological assay able to capture these interactions. It consists in analysing the effect of heat treatment on proteins. Indeed, proteins, under physiological conditions, are folded. This folding gets disrupted as the temperature increases. The way this unfolding happens, called the melting profile of the protein, informs on the interactions of proteins. For example, the interaction of a protein with another protein can increase (thermally stabilise) or decrease (thermally destabilise) the temperature at which this protein starts unfolding. In this work, we present a new statistical method, named GPMelt, to analyse these melting profiles. Notably, GPMelt allows to analyse any melting profiles, independently of their shapes. The proposed improvements over previously published methods allow to investigate more robustly the melting profiles of more proteins, hence increasing the ability of thermal proteome profiling assays to discover new protein interactions. We anticipate that these advancements will aid in unravelling complex biological phenomena.
Identification of potential distribution area for the sweet cherry (Prunus avium) by the MaxEnt model
Authors: Li Hongqun , Peng Xiaolong , Jiang Peng , Xing Ligang 
Published: October 2023

AbstractThe potential distribution of species offers important information for species management, especially for fruit trees with economic value. The sweet cherry is a tree species with higher economic value among deciduous fruit trees in north China. Herein, its potential distributions were modeled under current conditions. The performances of this model were excellent with AUCs of >0.9 for model training and testing. The key factors identified were the thermal factors (min temperature of coldest month (bio06) from -14.5 to 4.5°C, the mean temperature of warmest quarter (bio10) from 21.0 to 28.0°C), followed by water factor (the annual precipitation (bio12) from 500 to 1200 mm). Its suitable region in China mainly is located on 6 geographical regions including southwest China (eastern Sichuan, northeast and main urban areas of Chongqing, mid-western Guizhou and mid-northern Yunnan), northwest China (mid-southern Shaanxi, southern Ningxia mid-southern and eastern Gansu), northeast China (Coastal region of Liaoning), central China (most of Henan, mid-northern Hubei and central Hunan), north China (Beijing, Tianjing, mid-southern Shanxi), east China (Shanghai, Jiangsu, Shandong, central Zhejiang, central and northern Anhui and eastern Jiangxi) and south China (western Guangxi). Relative to their actual distributions, Hubei, Hunan and Anhui etc have been identified to have some potentially suitable areas for these sweet cherries. Among them, these 9 provinces or cities (Shaanxi, Beijing, Tianjing, Shanxi, Hebei, Henan, Shanghai, Jiangsu and Shandong) are main regions for its current development and utilization, followed by Sichuan, Guizhou,Yunnan, Gansu, Liaoning, Hubei, Zhejiang and Guangxi etc. The results can be adopted to identify the suitable areas for its introduction and cultivation to avoid the losses of human labor, material and financial resources due to improper decision, and to provide a scientific basis for its current introduction, cultivation and management.
Parkin R274W mutation affects muscle physiology via the PARIS-PGC-1α pathway
Authors: Sevegnani Martina , Lama Adriano , Girardi Francesco , Hess Michael W. , Castelo Maria Paulina , Pichler Irene , Biressi Stefano , Piccoli Giovanni 
Published: October 2023

AbstractRecessive mutations in the Parkin gene (PRKN) are the most common cause of young-onset inherited parkinsonism. Parkin is a multifunctional E3 ubiquitin ligase that plays a variety of roles in the cell including the degradation of proteins and the maintenance of mitochondrial homeostasis, integrity, and biogenesis via the PARIS-PGC-1α pathway. In 2001 the R275W mutation in thePRKNgene was identified in two unrelated families with a multigenerational history of postural tremor, dystonia and parkinsonism. Drosophila models of Parkin R275W showed selective and progressive degeneration of dopaminergic neuronal clusters, mitochondrial abnormalities, and prominent climbing defects. In the Prkn mouse orthologue, the amino acid R274 corresponds to human R275. Here we described a muscle phenotype in R274W +/+ mice and discovered that a defective Parkin-PARIS-PGC-1α pathway may impact mitochondrial biogenesis and, eventually, myoblast proliferation and differentiation.
Enrichment of Rare and Uncommon Neanderthal Polymorphisms in Autistic Probands and Siblings
Authors: Pauly Rini , Johnson Layla , Feltus F. Alex , Casanova Emily L. 
Published: October 2023

ABSTRACTHomo sapiensand Neanderthals underwent hybridization during the Middle/Upper Paleolithic age, culminating in retention of small amounts of Neanderthal-derived DNA in the modern human genome. In the current study, we address the potential roles genic Neanderthal single nucleotide polymorphisms (SNP) may be playing in autism susceptibility using data from the Simons Foundation Powering Autism Research (SPARK) and Genotype-Tissue Expression (GTEx) databases. We have discovered that rare and uncommon variants are significantly enriched in both European- and African-American autistic probands and their unaffected siblings compared to race-matched controls. In addition, we have identified 51 SNPs (p51) significantly enriched in European-American cases of autism, 13 of which fall within autism-associated genes, as well as 1 SNP in African-American probands. In addition, SNPs within the p51 network display significant linkage disequilibrium with one another, indicating they may more often be co-inherited in autism. These results strongly suggest Neanderthal-derived DNA is playing a significant role in autism susceptibility across major populations in the United States.
Metabolic interactions of a minimal bacterial consortium drive robust nitritation at acidic pH
Authors: Ni Gaofeng , Su Zicheng , Wang Yu , Wang Zhiyao , Wu Mengxiong , Hua Zhengshuang , Hu Shihu , Yuan Zhiguo , Guo Jianhua , Greening Chris , Zheng Min 
Published: October 2023

AbstractMicrobial communities efficiently mediate aerobic ammonia oxidation even at acidic pH. However, little is known about the adaptations and interactions that allow these communities to withstand challenges such as acidic stress, reactive nitrogen species, and resource deprivation under such conditions. Here we combined metagenomic analysis and biogeochemical measurements to infer the composition, metabolic interactions, and stress adaptation mechanisms of microbial consortia in three acidic nitritation bioreactors, operating at pH 5 to 2. This resulted in the recovery of 70 high-quality and mostly novel metagenome-assembled genomes (MAGs). The dominant ammonia oxidiser across all three bioreactors was a novel proteobacterium, herein named Candidatus (Ca.) Nitrosoglobus kelleri, that we enriched to a relative abundance of 55%. Also present were several heterotrophic bacteria that are predicted to engage in metabolically cross-feeding with theNitrosoglobus. Particularly abundant were mycobacteria, including the novel actinobacteriumCa. Mycobacterium cookii, which are predicted to use organic carbon, hydrogen, carbon monoxide, sulfide and possibly nitrite as energy sources to drive aerobic respiration and denitrification. Remarkably, we observed efficient conversion of ammonia to nitrate even at pH 2, by a minimalistic community comprising theNitrosoglobusandMycobacteriumas its only core members. Genomic analysis suggests these bacteria each use multiple strategies to maintain intracellular pH homeostasis, detoxify reactive nitrogen species, and scavenge nutrients at this pH. Altogether, these findings reveal that minimal communities can drive a key biogeochemical process even at acidic pH, and have implications for understanding nitrogen cycling and enhancing wastewater treatment.
Cilostazol may be a better therapeutic agent for acute ischemic stroke because of its efficacy in preventing post-stroke depression
Authors: Zhang Yuling , Yang Ganggang , Wang Rui , Wang Xin , Tan Xiying , Tang Chaozhi 
Published: October 2023

AbstractPost-stroke depression (PSD) has more than 1/3 complications in ischemic stroke (IS) patients, but there is still no specific drug that can effectively prevent the occurrence of PSD. Cilostazol, commonly used in the treatment of IS, has been found to rescue cognition impairment in recent years, but whether it has the efficacy in preventing PSD remains uncertain. In this study, a total of 431 acute ischemic stroke (AIS) patients treated with and without cilostazol during 2021-2022 were recruited and followed up for 6 months. At the end of follow-up, we found that AIS patients of cilostazol-treated group had significantly lower National Institutes of Health Stroke Scale (NIHSS) and 24-item Hamilton’s Depression Scale (HAMDS) scores than patients of cilostazol-free group (p<0.05), the total incidence of depression was 15.47% in patients of cilostazol-treated group and 36.02% in patients of cilostazol-free group, including 8.84% and 16.67% mild depression (p<0.05), 6.08% and 12.90% moderate depression (p<0.05), 0.55% and 6.45% major depression (p<0.01), respectively. In addition, the plasma levels of high-sensitive C-reactive protein (Hs-CRP), homocysteine (HCY), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and neutrophil/lymphocyte ratio (NLR) in AIS patients of cilostazol-treated group were all lower than those in patients of cilostazol-free group (p<0.05). These results suggest that cilostazol is a better therapeutic agent for AIS because it may prevent PSD by decreasing the levels of inflammation in patients.
The mitochondrial mRNA stabilizing protein, SLIRP, regulates skeletal muscle mitochondrial structure and respiration by exercise-recoverable mechanisms
Authors: Pham Tang Cam Phung , Raun Steffen Henning , Havula Essi , Henriquez-Olguín Carlos , Rubalcava-Gracia Diana , Frank Emma , Fritzen Andreas Mæchel , Jannig Paulo R. , Andersen Nicoline Resen , Kruse Rikke , Ali Mona Sadek , Halling Jens Frey , Ringholm Stine , Needham Elise J. , Hansen Solvejg , Lemminger Anders Krogh , Schjerling Peter , Petersen Maria Houborg , de Almeida Martin Eisemann , Jensen Thomas Elbenhardt , Kiens Bente , Hostrup Morten , Larsen Steen , Ørtenblad Niels , Højlund Kurt , Kjær Michael , Ruas Jorge L. , Trifunovic Aleksandra , Wojtaszewski Jørgen Frank Pind , Nielsen Joachim , Qvortrup Klaus , Pilegaard Henriette , Richter Erik Arne , Sylow Lykke 
Published: October 2023

Summary and graphical abstractDecline in mitochondrial function associates with decreased muscle mass and strength in multiple conditions, including sarcopenia and type 2 diabetes. Optimal treatment could include improving mitochondrial function, however, there are limited and equivocal data regarding the molecular cues controlling muscle mitochondrial plasticity. Here we uncover the mitochondrial-mRNA-stabilizing protein SLIRP, in complex with LRPPRC, as a PGC-1α target that regulates mitochondrial structure, respiration, and mitochondrially-encoded-mRNA pools in skeletal muscle. Exercise training effectively counteracted mitochondrial defects induced by loss of LRPPRC/SLIRP, despite sustained low mitochondrially-encoded-mRNA pools, via increased mitoribosome translation capacity. In humans, exercise training robustly increased muscle SLIRP and LRPPRC protein content across exercise modalities and sexes, yet this increase was less prominent in subjects with type 2 diabetes. Our work identifies a mechanism of post-transcriptional mitochondrial regulation in skeletal muscle through mitochondrial mRNA stabilization. It emphasizes exercise as an effective approach to alleviate mitochondrial defects by possibly increasing mitoribosome capacity.Abstract Figure
Neural manifolds carry reactivation of phonetic representations during semantic processing
Authors: Orepic Pavo , Truccolo Wilson , Halgren Eric , Cash Sydney S. , Giraud Anne-Lise , Proix Timothée 
Published: October 2023

AbstractTraditional models of speech perception posit that neural activity encodes speech through a hierarchy of cognitive processes, from low-level representations of acoustic and phonetic features to high-level semantic encoding. Yet it remains unknown how neural representations are transformed across levels of the speech hierarchy. Here, we analyzed unique microelectrode array recordings of neuronal spiking activity from the human left anterior superior temporal gyrus, a brain region at the interface between phonetic and semantic speech processing, during a semantic categorization task and natural speech perception. We identified distinct neural manifolds for semantic and phonetic features, with a functional separation of the corresponding low-dimensional trajectories. Moreover, phonetic and semantic representations were encoded concurrently and reflected in power increases in the beta and low-gamma local field potentials, suggesting top-down predictive and bottom-up cumulative processes. Our results are the first to demonstrate mechanisms for hierarchical speech transformations that are specific to neuronal population dynamics.
Root phosphatase activity is coordinated with the root conservation gradient across a phosphorus gradient in a lowland tropical forest
Authors: Guilbeault-Mayers Xavier , Laliberté Etienne 
Published: October 2023

AbstractSoil phosphorus (P) is a growth-limiting nutrient in tropical ecosystems, driving diverse P-acquisition strategies among plants. Particularly, mining for inorganic P through phosphomonoesterase (PME) activity is essential, given the substantial proportion of organic P in soils. Yet the relationship between PME activity and other P-acquisition root traits remains unclear.We measured root PME activity and commonly-measured root traits, including root diameter, specific root length (SRL), root tissue density (RTD), and nitrogen concentration ([N]) in 18 co-occurring trees across soils with varying P availability to better understand trees response to P supply.Root [N] and RTD were inversely related, and that axis was related to soil P supply. Indeed, both traits correlated positively and negatively to PME activity, which responded strongly to P supply. Conversely, root diameter was inversely related to SRL, but this axis was not related to P supply.Suggesting that limiting similarity influenced variation along the diameter-SRL axis, explaining high local trait diversity. Meanwhile, environmental filtering tended to impact trait values along the root [N]-RTD axis. Overall, P availability indicator traits like PME activity and root hairs only tended to be associated with these axes, highlighting limitations of these axes in describing convergent adaptations at local sites.
The Evolution of Heteroresistance via Small Colony Variants inEscherichia coliFollowing Long Term Exposure to Bacteriostatic Antibiotics
Authors: Gil-Gil Teresa , Berryhill Brandon A. , Manuel Joshua A. , Smith Andrew P. , McCall Ingrid C. , Baquero Fernando , Levin Bruce R. 
Published: October 2023

AbstractTraditionally, bacteriostatic antibiotics are agents able to arrest bacterial growth. Despite being traditionally viewed as unable to kill bacterial cells, when they are used clinically the outcome of these drugs is frequently as effective as when a bactericidal drug is used. We explore the dynamics ofEscherichia coliafter exposure to two ribosome-targeting bacteriostatic antibiotics, chloramphenicol and azithromycin, for thirty days. The results of our experiments provide evidence that bacteria exposed to these drugs replicate, evolve, and generate a sub-population of small colony variants (SCVs) which are resistant to multiple drugs. These SCVs contribute to the evolution of heteroresistance and rapidly revert to a susceptible state once the antibiotic is removed. Stated another way, exposure to bacteriostatic drugs selects for the evolution of heteroresistance in populations previously lacking this trait. More generally, our results question the definition of bacteriostasis as populations exposed to bacteriostatic drugs are replicating despite the lack of net growth.
A virally encoded high resolution screen of cytomegalovirus host dependencies
Authors: Finkel Yaara , Nachshon Aharon , Aharon Einav , Arazi Tamar , Simonovsky Elena , Dobesova Martina , Gluck Avi , Fisher Tal , Stanton Richard J. , Schwartz Michal , Stern-Ginossar Noam 
Published: October 2023

AbstractGenetic screens have transformed our ability to interrogate cellular factor requirements in infection, yet current approaches are limited in their sensitivity, biased towards early stages of infection and provide only simplistic phenotypic information which is often based on infected cell survival. Here, by engineering human cytomegalovirus to express sgRNA libraries directly from the viral genome, we developed a sensitive, versatile, viral centric approach that allows profiling of different stages along viral infection in a pooled format. Using this approach, which we termed VECOS (Virus Encoded CRISPR-based direct readOut Screening system), we identified hundreds of novel host dependency and restriction factors and quantified their direct effects on viral genome replication, viral particle secretion and infectiousness of secreted particles, providing a multi-dimensional perspective on viral-host interactions. These high resolution measurements reveal that perturbations that alter late stages in HCMV life cycle mostly regulate HCMV particle quality rather than quantity, defining correct virion assembly as a critical stage that is heavily reliant on viral-host interactions. Overall, VECOS facilitates systematic high resolution dissection of human proteins’ role along the infection cycle, providing a roadmap for in-depth dissection of host–herpesvirus interactions.
Hydroponics: A Novel Approach to CulturingAphanomyces euteiches
Authors: Done Ethan 
Published: October 2023

ABSTRACTAphanomyces euteichesis a soil-borne, economically impactful pathogen that afflicts pulse crops. Isolating it from environmental soil samples is made difficult by other microorganisms naturally present in field soil, particularlyRhizopus, that outcompete it on selective media. However, by isolating and culturingA. euteichesfrom pea plants grown in a hydroponics apparatus inoculated with field soil, this can be ameliorated to allow for enhanced observation and culturing ofA. euteichesin media. This experiment tested and validated a method of hydroponic growth forA. euteiches, and confirmed that it yieldedA. euteichesisolates using universal CPN60 sequencing.