bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline mutation rate predicts cancer mortality across 37 vertebrate species
Authors: Kapsetaki Stefania E. , Compton Zachary T. , Mellon Walker , Vincze Orsolya , Giraudeau Mathieu , Harrison Tara M. , Abegglen Lisa M. , Boddy Amy M. , Maley Carlo C. , Schiffman Joshua D. 
Published: August 2023

AbstractThe explanation for why some species are more susceptible to cancer than others remains an area of intense investigation. Cancer evolves in part through the accumulation of mutations and, therefore, we hypothesized that germline mutation rates would be associated with cancer prevalence and mortality across species. We collected previously published data on germline mutation rate and cancer mortality data for 37 vertebrate species. Germline mutation rate was positively correlated with cancer mortality (P= 0.008). Why animals with increased germline mutation rates die more from cancer remains an open question, however they may benefit from close monitoring for tumors due to hereditary cancer predisposition syndromes. Early diagnoses of cancer in these species may increase their chances of treatment and overall survival.
The interplay between focus of attention, respiratory phases, and the Heartbeat Evoked Potential
Authors: Zaccaro Andrea , della Penna Francesca , Mussini Elena , Parrotta Eleonora , Perrucci Mauro Gianni , Costantini Marcello , Ferri Francesca 
Published: August 2023

AbstractThe Heartbeat Evoked Potential (HEP) is an EEG fluctuation that reflects the cortical processing of cardiac signals. HEP amplitude increases during various tasks involving cardiac interoception. Recent research has also indicated that HEP amplitude and cardiac interoceptive accuracy are higher during exhalation compared to inhalation. This difference may be due to the suppression of heartbeat-related sensations during inhalation and the amplification of sensations during exhalation through attentional mechanisms. Despite significant advancements in HEP research, the interactions between the HEP, interoceptive attention, and respiration are still unclear. In this study, we developed a novel experimental paradigm to investigate the relationship between HEP amplitude and respiratory phases during tasks that involve attention to cardiac interoception, non-cardiac interoception (specifically, respiration), and exteroceptive stimuli. The tasks included the Heartbeat Counting Task and the Breath Counting Task as interoceptive tasks, as well as the Cardiac-Tone Counting Task and the Breath-Tone Counting Task as exteroceptive tasks. Results demonstrated significant increases in HEP amplitude during the Heartbeat Counting Task compared to the Cardiac-Tone Counting Task and the Breath Counting Task, mostly observed over fronto-central electrodes in a late time-window. Notably, the amplitude increases during the Heartbeat Counting Task were primarily driven by HEPs recorded during exhalation, while inhalation had minimal impact. These findings align with the predictive coding model of interoceptive perception, suggesting that HEP amplitude reflects a precision-weighting process of prediction errors related to cardiac sensations that is specifically influenced by attention directed toward the heart. Furthermore, our findings emphasize the crucial role of exhalation in this precision-weighting process. These results may have considerable implications for the development of respiratory interventions to fine-tune cardiac interoception.
Action space restructures visual working memory in prefrontal cortex
Authors: Jonikaitis Donatas , Zhu Shude 
Published: August 2023

AbstractVisual working memory enables flexible behavior by decoupling sensory stimuli from behavioral actions. While previous studies have predominantly focused on the storage component of working memory, the role of future actions in shaping working memory remains unknown. To answer this question, we used two working memory tasks that allowed the dissociation of sensory and action components of working memory. We measured behavioral performance and neuronal activity in the macaque prefrontal cortex area, frontal eye fields. We show that the action space reshapes working memory, as evidenced by distinct patterns of memory tuning and attentional orienting between the two tasks. Notably, neuronal activity during the working memory period predicted future behavior and exhibited mixed selectivity in relation to the sensory space but linear selectivity relative to the action space. This linear selectivity was achieved through the rapid transformation from sensory to action space and was subsequently maintained as a stable cross-temporal population activity pattern. Combined, we provide direct physiological evidence of the action-oriented nature of frontal eye field neurons during memory tasks and demonstrate that the anticipation of behavioral outcomes plays a significant role in transforming and maintaining the contents of visual working memory.
Secretory protein Rv1987, a ‘probable chitinase’ fromMycobacterium tuberculosisis a novel chitin and cellulose binding protein lacking enzymatic function
Authors: Prakash Chiranth M. , Janakiraman Vani 
Published: August 2023

AbstractBacterial chitinases serve to hydrolyse chitin as food source or as defence mechanism. Given that chitin is not produced by mammals, it is intriguing thatMycobacterium tuberculosis, an exclusively human pathogen harbours Rv1987, a probable chitinase and secretes it. Interestingly genes annotated as chitinases are widely distributed amongMycobacterium tuberculosiscomplex species, clinical isolates and other human pathogensM. abscessusandM. ulcerans. However, Mycobacterial chitinases are not characterized and hence the functions remain unknown. In the present study, we show that Rv1987 is a chitin and cellulose binding protein lacking enzymatic activity in contrary to its current annotation. Further, we show Rv1987 has moon lighting functions inM. tuberculosispathobiology signifying roles of bacterial cellulose binding clusters in infections.
Mechanical force regulates ligand binding and function of PD-1
Authors: Li Kaitao , Cardenas-Lizana Paul , Kellner Anna V. , Yuan Zhou , Ahn Eunseon , Lyu Jintian , Li Zhenhai , Salaita Khalid , Ahmed Rafi , Zhu Cheng 
Published: August 2023

AbstractImmune checkpoint blockade targeting PD-1 shows great success in cancer therapy. However, the mechanism of how ligand binding initiates PD-1 signaling remains unclear. As prognosis markers of multiple cancers, soluble PD-L1 is found in patient sera and can bind PD-1, but fails to suppress T cell function. This and our previous observations that T cells exert endogenous forces on PD-1– PD-L2 bonds prompt the hypothesis that mechanical force might be critical to PD-1 triggering, which is missing in the soluble ligand case due to the lack of mechanical support afforded by surface-anchored ligand. Here we show that PD-1 function is eliminated or reduced when mechanical support on ligand is removed or dampened, respectively. Force spectroscopic analysis reveals that PD-1 forms catch bonds with both PD-Ligands <7 pN where force prolongs bond lifetime, but slip bonds >8 pN where force accelerates dissociation. Steered molecular dynamics finds PD-1–PD-L2 complex very sensitive to force due to the two molecules’ “side-to-side” binding via β sheets. Pulling causes relative rotation and translation between the two molecules by stretching and aligning the complex along the force direction, yielding new atomic contacts not observed in the crystal structure. Compared to wild-type, PD-1 mutants targeting the force-induced new interactions maintain the same binding affinity but display lower rupture force, shorter bond lifetime, reduced tension, and most importantly, impaired capacity to suppress T cell activation. Our results uncover a mechanism for cells to probe the mechanical support of PD-1–PD-Ligand bonds using endogenous forces to regulate PD-1 triggering.
The Selenoproteome as a dynamic response mechanism to oxidative stress in methanogenic communities
Authors: Kleikamp Hugo , Palacios Paola A. , Papaharalabos George , Bentien Anders , Kofoed Michael V. W. , Nielsen Jeppe L. 
Published: August 2023

AbstractMethanogenesis is a critical process in the carbon cycle that is applied industrially in anaerobic digestion and biogas production. While naturally occurring in diverse environments, methanogenesis requires anaerobic and reduced conditions though varying degrees of oxygen tolerance have been described. Micro-aeration is touted as the next step to increase methane production and improve hydrolysis in digestion processes; therefore, a deeper understanding of the methanogenic response to oxygen stress is needed. In order to explore the drivers of oxygen tolerance in methanogenesis, two parallel enrichments were performed in an environment without reducing agents and in a redox-controlled environment by adding redox mediator AQDS. The cellular response to oxidative conditions is mapped using proteomic analysis. The resulting community showed remarkable tolerance to high-redox environments and was unperturbed in its methane production. Next to expressing pathways to mitigate reactive oxygen species, the higher redox potential environment showed an increased presence of selenocysteine and selenium-associated pathways. By including sulfur-to-selenium mass shifts in a proteomic database search, we provide the first evidence of dynamic and large-scale incorporation of selenocysteine as a response to oxidative stress by methanogenic organisms and the presence of a dynamic selenoproteome.
Does urbanization lead to parallel demographic shifts across the world in a cosmopolitan plant?
Authors: Caizergues Aude E. , Santangelo James S. , Ness Rob W. , Angeoletto Fabio , Anstett Daniel , Anstett Julia , Baena-Diaz Fernanda , Carlen Elizabeth J. , Chaves Jaime A. , Comerford Mattheau S. , Dyson Karen , Falahati-Anbaran Mohsen , Fellowes Mark D.E. , Hodgins Kathryn A. , Hood Glen R. , Iñiguez-Armijos Carlos , Kooyers Nicholas J. , Lázaro-Lobo Adrián , Moles Angela T. , Munshi-South Jason , Paule Juraj , Porth Ilga M. , Santiago-Rosario Luis Y. , Whitney Kaitlin Stack , Tack Ayko J.M. , Johnson Marc T.J. 
Published: August 2023

ABSTRACTUrbanization is occurring globally, leading to dramatic environmental changes that are altering the ecology and evolution of species. In particular, the expansion of human infrastructure and the loss and fragmentation of natural habitats in cities is predicted to increase genetic drift and reduce gene flow by reducing the size and connectivity of populations. Alternatively, the “urban facilitation model” suggests that some species will have greater gene flow into and within cities leading to higher diversity and lower differentiation in urban populations. These alternative hypotheses have not been contrasted across multiple cities. Here, we used the genomic data from the Global Urban Evolution project (GLUE), to study the effects of urbanization on non-adaptive evolutionary processes of white clover (Trifolium repens) at a global scale. We found that white clover populations presented high genetic diversity and no evidence of a reduction inNelinked to urbanization. On the contrary, we found that urban populations were less likely to experience a recent decrease in effective population size than rural ones. In addition, we found little genetic structure among populations both globally and between urban and rural populations, which showed extensive gene flow between habitats. Interestingly, white clover displayed overall higher gene flow within urban areas than within rural habitats. Our study provides one of the largest comprehensive tests of demographic effects of urbanization and our results contrast the common perception that heavily altered and fragmented urban environments will reduce the effective population size and genetic diversity of populations and contribute to their isolation.
LrhA promotes CRISPR-Cas immunity by enhancing primed adaptation inEscherichia coli
Authors: Fang Mengdie , Li Na , Gong Mengxin , Fei Mingyue , Lu Yalan , Yu Mingjing , Wu Fabai , Sun Dongchang 
Published: August 2023

ABSTRACTThe CRISPR-based defense system protects prokaryotes against foreign genetic elements. Previous studies indicated that the activity of the CRISPR-Cas system is the outcome of the combined effect of adaptation and interference. However, it remains unclear how coordination of the two processes is regulated to optimize the efficacy of adaptive immunity. Here, we identify the LysR-type transcriptional regulator LrhA as a new CRISPR-Cas activator which plays an important role in coordinating adaptation and interference. Through directly binding to the promoter of thecasoperon, LrhA enhances the CRISPR-Cas adaptive immunity against bacteriophage infection by stimulating the transcription ofcasgenes. Moderate activation ofcasgenes by LrhA efficiently promoted the clearance of horizontally transferred CRISPR-targeted plasmid via increasing the acquisition of new spacers by interference-driven adaptation inEscherichia coli. Our results indicate that intermediate level of transcription ofcasgenes achieved optimal outcomes of the adaptive immunity through triggering positive feedback between adaptation and interference, highlighting the importance of fine-tuning expression of CRISPR-Cas system.
The information theory formalism unifies the detection of the patterns of sexual selection and assortative mating for both discrete and quantitative traits
Authors: Carvajal-Rodríguez A. 
Published: August 2023

AbstractSexual selection plays a crucial role in modern evolutionary theory, offering valuable insight into evolutionary patterns and species diversity. Recently, a comprehensive definition of sexual selection has been proposed, defining it as any selection that arises from fitness differences associated with nonrandom success in the competition for access to gametes for fertilization. Previous research on discrete traits demonstrated that non-random mating can be effectively quantified using Jeffreys (or symmetrized Kullback-Leibler) divergence, capturing information acquired through mating influenced by mutual mating propensities instead of random occurrences. This novel theoretical framework allows for detecting and assessing the strength of sexual selection and assortative mating.In this study, we aim to achieve two primary objectives. Firstly, we demonstrate the seamless alignment of the previous theoretical development, rooted in information theory and mutual mating propensity, with the aforementioned definition of sexual selection. Secondly, we extend the theory to encompass quantitative traits. Our findings reveal that sexual selection and assortative mating can be quantified effectively for quantitative traits by measuring the information gain relative to the random mating pattern. The connection of the information indices of sexual selection with the classical measures of sexual selection is established.Additionally, if mating traits are normally distributed, the measure capturing the underlying information of assortative mating is a function of the square of the correlation coefficient, taking values within the non-negative real number set [0, +∞).It is worth noting that the same divergence measure captures information acquired through mating for both discrete and quantitative traits. This is interesting as it provides a common context and can help simplify the study of sexual selection patterns.
Structural and functional analysis of the minimal orthomyxovirus-like polymerase of Tilapia Lake Virus from the highly divergedAmnoonviridaefamily
Authors: Arragain Benoit , Pelosse Martin , Thompson Albert , Cusack Stephen 
Published: August 2023

AbstractTilapia Lake Virus (TiLV), a recently discovered pathogen of tilapia fish, belongs to theAmnoonviridaefamily from theArticulaviralesorder. Its ten genome segments have characteristic conserved ends and encode proteins with no known homologues, apart from the segment 1, which encodes an orthomyxo-like RNA-dependent-RNA polymerase core subunit. Here we show that segments 1-3 encode respectively the PB1, PB2 and PA-like subunits of an active heterotrimeric polymerase that maintains all domains found in the distantly related influenza polymerase, despite an unprecedented overall size reduction of 40%. Multiple high-resolution cryo-EM structures of TiLV polymerase in pre-initiation, initiation and active elongation states, show how it binds the vRNA and cRNA promoters and performs RNA synthesis, with both transcriptase and replicase configurations being characterised. However, the highly truncated endonuclease-like domain appears inactive and the putative cap-binding domain is autoinhibited, emphasising that many functional aspects of TiLV polymerase remain to be elucidated.
SuperCellCyto: enabling efficient analysis of large scale cytometry datasets
Authors: Putri Givanna H. , Howitt George , Marsh-Wakefield Felix , Ashhurst Thomas M. , Phipson Belinda 
Published: August 2023

AbstractAdvancements in cytometry technologies have enabled quantification of up to 50 proteins across millions of cells at single cell resolution. Analysis of cytometry data routinely involves tasks such as data integration, clustering, and dimensionality reduction. While numerous tools exist, many require extensive run times when processing large cytometry data containing millions of cells. Existing solutions, such as random subsampling, are inadequate as they risk excluding rare cell subsets. To address this, we propose SuperCellCyto, an R package that builds on the SuperCell tool which groups highly similar cells into supercells. SuperCellCyto is available on GitHub (https://github.com/phipsonlab/SuperCellCyto).
Detecting adaptive changes in gene copy number distribution accompanying the human out-of-Africa expansion
Authors: Otto Moritz , Zheng Yichen , Grablowitz Paul , Wiehe Thomas 
Published: August 2023

AbstractGenes with multiple copies are likely to be maintained by stabilizing selection that puts a bound to unlimited expansion of copy number. We designed a model where copy number variation is generated by unequal recombination, which fits well to a number of genes, surveyed in three human populations. Based on this theoretical model and on computer simulations, we were interested in answering the question whether gene copy number distribution in the derived European and Asian populations can be explained by a purely demographic scenario or whether shifts in the distribution are signatures of adaptation. Although copy number distribution in most of the analyzed gene clusters can be explained by a bottleneck as in the out of Africa expansion of homo sapiens 60-10kyrs ago, we identified several candidate genes, for instanceAMY1AandPGA3, whose copy numbers are likely to be selected differently among African, Asian and European populations.
SAMD1 suppresses epithelial-mesenchymal transition (EMT) pathways in pancreatic ductal adenocarcinoma
Authors: Simon Clara , Brunke Inka D. , Stielow Bastian , Forné Ignasi , Steitz Anna Mary , Geller Merle , Rohner Iris , Weber Lisa M. , Fischer Sabrina , Jeude Lea Marie , Nist Andrea , Stiewe Thorsten , Huber Magdalena , Buchholz Malte , Liefke Robert 
Published: August 2023

AbstractSAMD1 (SAM-domain containing protein 1), a CpG island-binding protein, plays a pivotal role in the repression of its target genes. Despite its significant correlation with outcomes in various tumor types, the role of SAMD1 in cancer has remained largely unexplored. In this study we focused on pancreatic ductal adenocarcinoma (PDAC) and revealed that SAMD1 acts as a repressor of genes associated with epithelial-mesenchymal transition (EMT). Upon deletion of SAMD1 in PDAC cells, we observed significantly increased migration rates. SAMD1 exerts its effects by binding to specific genomic targets, includingCDH2, encoding N-cadherin, which emerged as a driver of enhanced migration upon SAMD1 knockout. Furthermore, we discovered the FBXO11-containing E3 ubiquitin ligase complex as an interactor of SAMD1. FBXO11 ubiquitinates SAMD1 within its DNA-binding winged helix domain and inhibits SAMD1 chromatin binding genome-wide. HighFBXO11expression in PDAC is associated with poor prognosis and increased expression of EMT-related genes, underlining an antagonistic relationship between SAMD1 and FBXO11. In summary, our findings provide new insights into the regulation of EMT-related genes in PDAC, shedding light on the intricate role of SAMD1 and its interplay with FBXO11 in this cancer type.
Txn1mutation is a monogenic cause of chronic kidney disease associated with mitochondrial dysfunction in rats
Authors: Ohmori Iori , Ouchida Mamoru , Hada Yoshiko , Uchida Haruhito A. , Toyokuni Shinya , Mashimo Tomoji 
Published: August 2023

AbstractOxidative stress plays a significant role in the progression of chronic kidney disease. Thioredoxin 1 (Txn1) is one of the enzymatic antioxidants to regulate redox balance. However, the molecular mechanisms by Txn1 affects renal homeostasis remain unclear. This study aimed at elucidating the pathophysiology ofTxn1mutations in renal function. We used rats with theTxn1-F54L mutation generated by N-ethyl-N-nitrosourea mutagenesis. Laboratory tests and pathological examinations were performed in wild-type (WT) rats and in rats with heterozygous and homozygousTxn1-F54L mutations. We performed RNA-seq analysis of the WT and homozygotes. To confirm phenotypic reproducibility, theTxn1-F54L mutation was generated in rats with different genetic backgrounds using CRISPR/Cas9 genome editing technology.Txn1-F54L mutant rats exhibited progressive albuminuria, hypoalbuminemia, hypercholesterolemia, and hypertension. Renal pathology revealed marked nephrosclerosis, tubular dilatation, interstitial fibrosis, and decreased number of mitochondria, mainly in the paroxysmal tubules. We confirmed a similar phenotype of chronic kidney disease (CKD) in different rat strains. RNA-seq showed the downregulation of mitochondria-related genes and significant upregulation of genes associated with inflammation, pyroptosis, apoptosis, and necroptosis in mutant rats. Our results show that theTxn1mutation is a monogenic cause of CKD termination. The underlying pathology involves several regulated cell-death pathways. Thus, our study provides a new animal model of oxidative stress-induced CKD.Txn1-F54L mutant rats will aid in developing therapeutic strategies for CKD.Translational StatementWe found that the deficiency of thioredoxin (Txn1), which regulates oxidative stress, spontaneously caused chronic kidney disease (CKD) in rats. The Txn1-F54L (Adem) rat is a new model of CKD with complications such as anemia, hypertension, and cardiovascular disease. Renal pathology revealed nephrosclerosis, interstitial fibrosis, and mitochondrial damage. The molecular basis of the underlying pathologies included inflammation, pyroptosis, apoptosis, and necroptosis. These pathological changes are partially linked to renal diseases such as diabetic nephropathy, hypertensive nephrosclerosis, and ischemic reperfusion injury.Ademrats could help understand the common pathological mechanisms of these renal diseases and develop therapeutic strategies.