bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inferring drift, genetic differentiation, and admixture graphs from low-depth sequencing data
Authors: Rasmussen Malthe Sebro , Wiuf Carsten , Albrechtsen Anders 
Published: January 2024

AbstractA number of popular methods for inferring the evolutionary relationship between populations require essentially two components: First, they require estimates off2-statistics, or some quantity that is a linear combination of these. Second, they require estimates of the variability of the statistic in question. Examples of methods in this class include qpGraph and TreeMix.It is known, however, that these statistics are biased when based on genotype calls at low depth. Moreover, as we show, this leads to downstream inference of significantly distorted trees. To solve this problem, we demonstrate how to accurately and efficiently compute a broad class of statistics from low-depth whole-genome sequencing data, including estimates of their standard errors, by using the site frequency spectrum. In particular, we focus onf2and the sample covariance of allele frequencies to show how this method leads to accurate estimate of drift when fitting trees using qpGraph and TreeMix with low-depth data. However, the same considerations lead to uncertainty estimates for a variety of other statistics, including heterozygosity, kinship estimates (e.g. King), and quantities relating to genetic differentiation such asFstandDxy.
An analysis of natural variation inPinus pinasterthrough the lens of systems biology
Authors: Pascual Jesús , López-Hidalgo Cristina , Feito Isabel , Majada Juan , Meijón Mónica 
Published: January 2024

AbstractPinus pinasteris a main species in Mediterranean forests, being naturally distributed through the Mediterranean basin, covering regions with a variety of geoclimatic conditions. This distribution in different environments leads, by natural selection, to a natural variation within the species that manifests at phenotypic level in populations with different growth features and overall tree architectures. StudyingP. pinasternatural variation is necessary to understand the genetic heritage of the species and can provide valuable information for information-based decision-making regarding forest management and breeding programmes. In this paper, we analyzed the natural variation in needles and buds from three provenances from contrasting geoclimatic locations using a common garden approach and proteomics. The integration of the proteomics data with tree growth-related parameters, geoclimatic features at provenances original locations, and sample-matched metabolomics data previously generated provided novel knowledge on metabolism rearrangements related to secondary metabolism and associated to growth features and the adaptation to light and UV-B radiation intensities.
The transcription factor IRF-5 is essential for the metabolic rewiring of CD8 T cells during chronic infection
Authors: Mai Linh Thuy , Swaminathan Sharada , Nguyen Trieu Hai , Charpentier Tania , Loucif Hamza , Carmona-Pérez Liseth , Lamarre Alain , Heinonen Krista M. , Fritz Jörg H. , Stäger Simona 
Published: January 2024

AbstractNumerous transcription factors are involved in promoting an intricate gene expression program that leads to CD8 T cell exhaustion. Here, we found that the transcription factor IRF-5 is involved in limiting functional exhaustion of CD8 T cells by regulating the cell cycle and contributing to sustaining the mitochondrial functions and oxidative phosphorylation during the chronic stage of LCMV Cl13 infection. CD8 T cells lacking IRF-5 display reduced survival capacity and show increased signs of functional exhaustion during the chronic stage of infection. IRF-5-deficiency also resulted in a severely defective lipid metabolism, in a faulty mitochondrial envelope, and in the reduced capacity to produce ATP. Additionally, we observed increased lipid peroxidation in CD8 T cells lacking IRF-5, when compared with WT cells. These findings identify IRF-5 as a pivotal regulator of the metabolic rewiring that occurs in CD8 T cells during the chronic stages of infection and highlight its role in protecting cells from cell death, possibly by lipid peroxidation.SummaryIRF-5 is critical for regulating mitochondrial functions and oxidative phosphorylation in CD8 T cells during chronic stages of LCMV Cl13 infection.
Revealing brain network dynamics during the emotional state of suspense using topological data analysis
Authors: Olave Astrid A. , Perea Jose A. , Gómez Francisco 
Published: January 2024

AbstractSuspense is an affective state ubiquitous in human life, from art to quotidian events. However, little is known about the behavior of large-scale brain networks during suspenseful experiences. To address this question, we examined the continuous brain responses of participants watching a suspenseful movie, along with reported levels of suspense from an independent set of viewers. We employ sliding window analysis and Pearson correlation to measure functional connectivity states over time. Then, we use Mapper, a topological data analysis tool, to obtain a graphical representation that captures the dynamical transitions of the brain across states; this representation enables the anchoring of the topological characteristics of the combinatorial object with the measured suspense. Our analysis revealed changes in functional connectivity within and between the salience, fronto-parietal, and default networks associated with suspense. In particular, the functional connectivity between the salience and fronto-parietal networks increased with the level of suspense. In contrast, the connections of both networks with the default network decreased. Together, our findings reveal specific dynamical changes in functional connectivity at the network level associated with variation in suspense, and suggest topological data analysis as a potentially powerful tool for studying dynamic brain networks.
The actomyosin system is essential for the integrity of the endosomal system in bloodstream formTrypanosoma brucei
Authors: Link Fabian , Jung Sisco , Malzer Xenia , Zierhut Felix , Konle Antonia , Borges Alyssa , Batters Christopher , Weiland Monika , Pöllmann Mara , Nguyen An Binh , Kullmann Johannes , Veigel Claudia , Engstler Markus , Morriswood Brooke 
Published: January 2024

AbstractThe actin cytoskeleton is a ubiquitous feature of eukaryotic cells, yet its complexity varies across different taxa. In the parasitic protistTrypanosoma brucei, a rudimentary actomyosin system consisting of one actin gene and two myosin genes has been retained despite significant investment in the microtubule cytoskeleton. The functions of this highly simplified actomyosin system remain unclear, but appear to centre on the endomembrane system. Here, advanced light and electron microscopy imaging techniques together with biochemical and biophysical assays were used to explore the relationship between the actomyosin and endomembrane systems. The class I myosin (TbMyo1) had a large cytosolic pool and its ability to translocate actin filamentsin vitrowas shown here for the first time. TbMyo1 exhibited strong association with the endosomal system and was additionally found on glycosomes. At the endosomal membranes, TbMyo1 colocalised with markers for early and late endosomes (TbRab5A and TbRab7, respectively), but not with the marker associated with recycling endosomes (TbRab11). Actin and myosin were simultaneously visualised for the first time in trypanosomes using an anti-actin chromobody. Disruption of the actomyosin system using the actin-depolymerising drug latrunculin A resulted in a delocalisation of both the actin chromobody signal and an endosomal marker, and was accompanied by a specific loss of endosomal structure. This suggests that the actomyosin system is required for maintaining endosomal integrity inT. brucei.
Coordinate regulation of Activin and Bone Morphogenetic Protein signaling by a lysosomal trafficking switch
Authors: Hom Warren W. , Aykul Senem , Panagis Lampros , Patel Krunal , Brydges Susannah , Goebel Erich J. , Lydon Kaitlin N. , Lees-Shepard John B. , Hatsell Sarah J. , Idone Vincent , Economides Aris N. 
Published: January 2024

AbstractBMP/TGFß family ligands act mainly as factors that differentially initiate Smad1/5/8 or Smad2/3 signaling via heterotetrameric complexes comprised of two type I and two type II receptors (IIR). ActA (ActA) stands out as it activates Smad2/3 signaling through type I receptor ACVR1B, whereas it generates non-signaling complexes (NSCs) with ACVR1. In fibrodysplasia ossificans progressiva (FOP), a genetic disorder caused by missense mutations in ACVR1 (ACVR1.FOP), ACVR1.FOP•ActA•IIR complexes activate Smad1/5 signaling, mimicking those formed with BMPs. As the NSCs that ActA forms with ACVR1 are stoichiometrically identical with signaling complexes formed with ACVR1.FOP, we explored how NSCs differ from their signaling counterparts. We show that ACVR1•ActA•IIR complexes rapidly traffic to lysosomes, where their constituent components are degraded, reducing the cell’s responsiveness to BMPs along with ActA’s availability. This property is specific to ActA as Activin B, AB, and AC do not form lysosomal trafficking complexes with ACVR1, but rather remain on the surface as NSCs. Lysosomal trafficking and degradation of ACVR1•ActA•IIR complexes is a novel regulatory mechanism of BMP/TGFß signaling whose physiological roles remain largely unexplored.
Putrescine acts as a signaling metabolite in the transition from nodulation to nitrogen fixation inRhizobium phaseoli
Authors: Hernandez-Benitez Ericka M. , Martínez-Romero Esperanza , Aguirre-Noyola José Luis , Ledezma-Tejeida Daniela 
Published: January 2024

AbstractGrowth of the common bean plantPhaseolus vulgarisis tightly linked to its symbiotic relationship with diverse rhizobial species, particularlyRhizobium phaseoli, an alphaproteobacteria that forms root nodules and provides high levels of nitrogen to the plant. Molecular cross-talk is known to happen via plant-derived metabolites, but only flavonoids have been identified as signals. Flavonoids are transported inside the bacteria, where they signal the NodD regulator to elicit nodulation. Although seven other regulators are known to be involved, our knowledge of the regulatory mechanisms underlying the nodulation, and nitrogen fixation processes is limited, and the signals recognized by regulators are mostly unknown. Here, we identified 75 transcription factors inR. phaseoligenome through sequence conservation fromEscherichia coli, and assembled a transcriptional regulatory network comprising 24 regulators, and 652 target genes. We identified the interactions relevant to nodulation via gene expression, and signaled out putrescine as a signaling metabolite. We propose a model where putrescine acts as a switch on the transition from nodulation to nitrogen fixation via the dual transcription factor PuuR, and its regulation of thenodIandnifU2genes.ImportanceThis study provides new insights into the molecular cross-talk betweenPhaseolus vulgarisandRhizobium phaseoli, which is crucial for the development of alternative cropping strategies, including biopesticides and biofertilizers. In addition, we present the first transcriptional regulatory network systematically assembled forRhizobium phaseoli, which opens new avenues of research in the relationship between the transcriptional regulation and metabolism of these organisms.
A transcriptomic study of PF06830 root cap proteins
Authors: Raymond James A. 
Published: January 2024

AbstractPF06830 is a family of about 2000 root cap proteins (RCPs) that are almost certainly involved in the major functions of the root cap, which include root growth and development, obtaining nutrients and sensing environmental variables. They appear to be expressed in the outer cell layers of the root tip where they are in intimate contact with the soil. Surprisingly, almost nothing is known about their individual functions, and they have received virtually no attention since their first description a quarter century ago. RCPs have easily identifiable characteristics and can be found in almost all plant species. The enormous expansion of plant transcriptomes in recent years provides an opportunity to better understand their functions, i.e., to see what biotic and abiotic variables affect their expressions. Here, the expressions of RCP genes in 49 root transcriptome studies (representing 14 species) obtained under different environmental conditions and at different development stages were investigated. (deleted sentence) In 19 of these studies, RCP expressions were found to be positively affected by environmental or developmental factors in specific cultivars of Arabidopsis, barley, rye, wheat, rice and cucumber. However, several negative effects were also found, often in different cultivars of the same species. These studies represent a first step in understanding the functions of RCPs that should help in the design of further studies. RCPs share some structural properties with, and may have overlapping functions with, other plant protein families, including small heat shock proteins, late embryogenesis abundant proteins and lectins. Their origins appear to predate the development of roots.
New antiviral defences are genetically embedded within prokaryotic immune systems
Authors: Payne Leighton J. , Hughes Tom C. D. , Fineran Peter C. , Jackson Simon A. 
Published: January 2024

ABSTRACTBacteria and archaea typically have multiple defence systems that protect them against viral predation. Recently, many new defence systems have been discovered, yet the full scope of the prokaryotic pan-immune system remains to be determined. In this study, we observed that many multi-gene defence systems have additional genes nested or ‘embedded’ within them. Based on this observation, we present a new approach to predict new defence systems, where defence function of uncharacterised genes is inferred based on their genetic embedding in known defence systems. Applying this ‘guilt-by-embedding’ method, we identified and confirmed anti-phage function for seven defence systems and predicted 145 additional candidates. Our findings expand the known immune repertoire of prokaryotes, provide a wealth of new systems for future functional studies, and demonstrate a simple, efficient approach to identify new antiviral defences.
Spatiotemporal orchestration of Ca2+-cAMP oscillations on AKAP/AC nanodomains is governed by an incoherent feedforward loop
Authors: Qiao Lingxia , Getz Michael , Gross Ben , Tenner Brian , Zhang Jin , Rangamani Padmini 
Published: January 2024

AbstractThe nanoscale organization of enzymes associated with the dynamics of second messengers is critical for ensuring compartmentation and localization of signaling molecules in cells. Specifically, the spatiotemporal orchestration of cAMP and Ca2+oscillations is critical for many cellular functions. Previous experimental studies have shown that the formation of nanodomains of A-kinase anchoring protein 79/150 (AKAP150) and adenylyl cyclase 8 (AC8) on the surface of pancreatic MIN6 β cells modulates the phase of Ca2+-cAMP oscillations from out-of-phase to in-phase. In this work, we develop computational models of the Ca2+/cAMP pathway and AKAP/AC nanodomain formation that give rise to the two important predictions: instead of an arbitrary phase difference, the out-of-phase Ca2+/cAMP oscillation reaches Ca2+trough and cAMP peak simultaneously, which is defined as inversely out-of-phase; the in-phase and inversely out-of-phase oscillations associated with Ca2+-cAMP dynamics on and away from the nanodomains can be explained by an incoherent feedforward loop. Factors such as cellular surface-to-volume ratio, compartment size, and distance between nan-odomains do not affect the existence of in-phase or inversely out-of-phase Ca2+/cAMP oscillation, but cellular surface-to-volume ratio and compartment size can affect the time delay for the inversely out-of-phase Ca2+/cAMP oscillation while the distance between two nanodomains does not. Finally, we predict that both the Turing pattern-generated nanodomains and experimentally measured nan-odomains demonstrate the existence of in-phase and inversely out-of-phase Ca2+/cAMP oscillation when the AC8 is at a low level, consistent with the behavior of an incoherent feedforward loop. These findings unveil the key circuit motif that governs cAMP and Ca2+oscillations and advance our understanding of how nanodomains can lead to spatial compartmentation of second messengers.
Machine Learning-Based Identification of B4GALNT1 as a Key Player in Hepatocellular Carcinoma: A Comprehensive Bioinformatics and Structural Analysis
Authors: Verma Rohit Kumar , Lokhande Kiran Bharat , Srivastava Prashant Kumar , Singh Ashutosh 
Published: January 2024

AbstractLiver hepatocellular carcinoma (LIHC) is one of the most frequent types of malignant cancer in the globe. The identification of new biomarkers for the LIHC is critical. We used TCGA-LIHC gene expression datasets for this study. Several feature selection methods were used to find the top gene signatures that distinguish LIHC cancer from normal samples. Eleven machine learning algorithms were used on these selected characteristics, and model performance evaluation revealed that Naive Bayes Classifiers (AUC = 0.965) performs the best for a selection of 55 protein coding genes. Among 55 protein coding genes we found B4GALNT1 (Beta-1,4-N-acetyl-galactosaminyltransferase 1) which is differentially regulated in LIHC. With several evidence B4GALNT1 plays crucial role in tumorigenesis in many cancers, therefore we conducted systematic bioinformatics approach with mutational and structural analysis of B4GALNT1 in LIHC. Moreover, survival analysis, immune cell infiltration, most significant associated methylated CpG probe and access the accuracy of B4GALNT1 conducted to find the potential role of B4GALNT1. The results suggested that B4GALNT1 was significantly expressed in most cancers including LIHC. Finally, 16 missense mutations identified through cBioportal, Cosmic Database, and Human Variant Database, among which 6 mutations (P64Q, S131F, A311S, R340Q, D478H, and P507Q) found to be deleterious when analysed byin-silicoprediction algorithms such as SIFT, PolyPhen2, I Mutent2 and CADD in LIHC. Molecular Dynamics simulation analysis was performed to understand the atomic details of the structure and functional changes. Results from this study suggest the impact of these missense variants on the structure of the B4GALNT1 protein and its pathogenic relevance. Our study demonstrated that B4GALNT1 may be evaluated as a novel target for liver cancer therapy because it has been found to be overexpressed in Liver and correlates with a poor prognosis.
Low pre-infection levels of neutralizing antibody in breakthrough infections after bivalent BA.4-5 vaccine and practical application of dried blood spots
Authors: Kawasuji Hitoshi , Morinaga Yoshitomo , Tani Hideki , Yamada Hiroshi , Yoshida Yoshihiro , Ezaki Masayoshi , Koshiyama Yuki , Takegoshi Yusuke , Kaneda Makito , Murai Yushi , Kimoto Kou , Nagaoka Kentaro , Niimi Hideki , Yamamoto Yoshihiro 
Published: January 2024

ABSTRACTThe level of neutralizing antibodies required to confer protection against COVID-19 breakthrough infections (BIs) is unclear, and the ability to know the immune status of individuals against the rapidly changing endemic variants is limited. We assessed longitudinal serum anti-RBD antibody levels and neutralizing activities (NTs) against Omicron BA.5 and XBB.1.5 in healthcare workers following the fourth monovalent and fifth bivalent BA.4-5 vaccines. The occurrence of BIs was also followed, and pre-infection antibody levels were compared between patients who developed BI and those who did not. In addition, we collected whole blood samples on the same day as the sera and stored them on filter papers (nos. 545, 590, and 424) for up to two months, then measured their NTs using dried blood spots (DBS) eluates, and compared them with the NTs in paired sera. Pre-infection levels of NTs were lower in patients who developed BI than those who did not, but the anti-RBD antibody levels were not different between them. The NTs below 50% using 200-fold diluted sera might be one of the indicators of high risk for COVID-19 BI. However, the NTs against XBB.1.5 at 6 months after the fifth dose of bivalent BA.4-5 vaccine were lower than this threshold in almost half of infection-naïve participants. NTs measured using DBS eluates were strongly correlated with those measured using paired sera, but the time and temperature stability varied with the type of filter paper; no. 545 filter paper was found to most suitable for NT evaluation.
Information Bottlenecks in Forecasting COVID-19
Authors: Gamarnik David , Ma Muzhi 
Published: January 2024

Reliable short term and long term forecasting of the number of COVID-19 incidences is a task of clear importance. Numerous attempts for such forecasting have been attempted historically since the onset of the pandemic. While many successful short-term forecasting models have been put forward, predictions for mid-range time intervals (few weeks) and long-range ones (few months to half a year) appeared to be largely inaccurate.In this paper we investigate systematically the question as to what extend such predictions are even possible given the information available at the times when the predictions are made. We demonstrate that predictions on the daily basis is practically impossible beyond the horizon of 20+ days, and predictions on the weekly basis is similarly impossible beyond the horizon of roughly half a year. We arrive at this conclusion by computing information bottlenecks arising in the dynamics of the COVID-19 pandemic. Such bottlenecks stem from the “memoryless” property of the stochastic dynamical systems describing COVID-19 evolution, specifically from the so-called mixing rate of the system. The mixing rate is then used to gage the rate at which the information used at a time when predictions are made no longer impacts the actual outcomes of the pandemic.