bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-testing knowledge and beliefs on HIV self-testing use in central Uganda
Authors: Nsereko Gerald Mukisa , Kobusingye Loyce Kiiza , Musanje Khamisi , Nangendo Joanita , Nantamu Simon , Baluku Martin Mabunda 
Published: January 2024

AbstractThe government of Uganda and its implementing partners have made significant investments in HIV self-testing (HST) services to reduce clinic-related barriers to HIV testing. However, although HSTs have been around for a reasonable time, their uptake, especially among unskilled working individuals, has remained suboptimal, which threatens the efforts to achieve the 95-95-95 UNAIDS goals to end HIV by 2030.This study set out to examine whether knowledge and individual beliefs about self-testing influence the use of HIV self-tests among causal workers in Kampala. This cross-sectional study was conducted among 453 participants selected via systematic random sampling from Darling Uganda Ltd. in Wakiso district between July and August 2023. Standardized questionnaires were used, and the analysis was performed using Pearson Correlations and Linear Regression in SPSS.The findings indicate that HIV self-testing (HST) knowledge was positively related to HST use (r=.387, p≤.01), perceived susceptibility (r=.212, p≤.01), perceived benefits (r=.152, p≤.01), and perceived barriers (r=.101, p≤.05). Individual beliefs, that is, perceived susceptibility (r=.355, p≤.01), perceived benefits (r=.487, p≤.01), and perceived barriers (r=.148, p≤.01), were significantly related to HST use. Perceived benefits were the best predictor of HST use among this population (β=.442,p=.000). Therefore, (44.2%) of HST use was attributed to the benefits attached to the service.Therefore, increasing awareness regarding the benefits of HST among such populations increases the chances of HIV testing, particularly among men. This can pave the way for the 95-95-95 goal by 2030 of UNAIDS.
Experimental evaluation of a direct fitness effect of thede novoevolved mouse genePldi
Authors: Linnenbrink Miriam , Breton Gwenna , Misra Pallavi , Pfeifle Christine , Dutheil Julien Y. , Tautz Diethard 
Published: January 2024

AbstractDe novoevolved genes emerge from random non-coding sequences and have, therefore, no homologs from which a function could be inferred. While expression analysis and knockout experiments can provide insights into the function, they do not directly test whether the gene is beneficial for its carrier. Here, we have used a seminatural environment experiment to test the fitness of the previously identified denovoevolved mouse genePldi, which is thought to be involved in sperm differentiation. We used a knockout mouse strain for this gene and competed it against its parental wildtype strain for several generations of free reproduction. We found that the knockout (ko) allele frequency decreased consistently across three replicates of the experiment. Using an approximate Bayesian computation framework that simulated the data under a demographic scenario mimicking the experiment’s demography, we could estimate a fitness coefficient ranging between 0.15 to 0.67 for the wildtype allele compared to the ko allele in males. We conclude that a gene that has evolvedde novofrom a random intergenic sequence can have a measurable fitness benefit.
Value construction through sequential sampling explains serial dependencies in decision making
Authors: Zylberberg Ariel , Bakkour Akram , Shohamy Daphna , Shadlen Michael N 
Published: January 2024

AbstractMany decisions are expressed as a preference for one item over another. When these items are familiar, it is often assumed that the decision maker assigns a value to each of the items and chooses the item with the highest value. These values may be imperfectly recalled, but are assumed to be stable over the course of an interview or psychological experiment. Choices that are inconsistent with a stated valuation are thought to occur because of unspecified noise that corrupts the neural representation of value. Assuming that the noise is uncorrelated over time, the pattern of choices and response times in value-based decisions are modeled within the framework of Bounded Evidence Accumulation (BEA), similar to that used in perceptual decision-making. In BEA, noisy evidence samples accumulate over time until the accumulated evidence for one of the options reaches a threshold. Here, we argue that the assumption of temporally uncorrelated noise, while reasonable for perceptual decisions, is not reasonable for value-based decisions. Subjective values depend on the internal state of the decision maker, including their desires, needs, priorities, attentional state, and goals. These internal states may change over time, or undergo revaluation, as will the subjective values. We reasoned that these hypothetical value changes should be detectable in the pattern of choices made over a sequence of decisions. We reanalyzed data from a well-studied task in which participants were presented with pairs of snacks and asked to choose the one they preferred. Using a novel algorithm (Reval), we show that the subjective value of the items changes significantly during a short experimental session (about 1 hour). Values derived withRevalexplain choice and response time better than explicitly stated values. They also better explain the BOLD signal in the ventromedial prefrontal cortex, known to represent the value of decision alternatives. Revaluation is also observed in a BEA model in which successive evidence samples are not assumed to be independent. We argue that revaluation is a consequence of the process by which values are constructed during deliberation to resolve preference choices.
CD4 T Cells Acquire Cytotoxic Properties to Modulate Cellular Senescence and Aging
Authors: Elyahu Yehezqel , Feygin Ilana , Pinkas Noa , Zemer Alon , Shicht Amit , Berner Omer , Eremenko Ekaterina , Nemirovsky Anna , Reshef Keren , Roitman Lior , Krizhanovsky Valery , Monsonego Alon 
Published: January 2024

AbstractAging is characterized by the progressive deterioration of tissue structure and function, leading to increased vulnerability to diseases and, eventually, death. One prominent process in aging is the accumulation of senescent cells. Although the immune system has been recognized as crucial for the elimination of senescent cells, the associated mechanisms remain incompletely understood. Here we show that CD4 T cells differentiate into cytotoxic T lymphocytes (CTLs) in a senescent cell-rich environment and that a reduction in the senescent cell load, achieved using chemical senolytic drugs, was sufficient to halt this differentiation. We further demonstrate that eliminating CD4 CTLs in the context of late aging by selectively deleting the Eomes transcription factor in CD4 T cells resulted in the increased accumulation of senescent cells, profound physical deterioration, and a decreased life span. In liver cirrhosis, a model of localized chronic inflammation, CD4 CTL elimination increased the senescent load and worsened the disease. Collectively, our findings demonstrate the fundamental role of CD4 CTLs in modulating tissue senescence and unveil a new aspect of age-related T-cell biology implicated in disease susceptibility and longevity.
Intricate response dynamics enhances stimulus discrimination in the resource-limitedC. eleganschemosensory system
Authors: Bokman Eduard , Pritz Christian O. , Ruach Rotem , Itskovits Eyal , Sharvit Hadar , Zaslaver Alon 
Published: January 2024

SummarySensory systems evolved intricate designs to accurately encode perplexing environments. However, this encoding task may become particularly challenging for animals harboring a small number of sensory neurons. Here, we studied how the compact resource-limited chemosensory system ofC. elegansuniquely encodes a range of chemical stimuli. We find that each stimulus is encoded using a small and unique subset of neurons, where only a portion of the encoding neurons sense the stimulus directly, and the rest are recruited via inter-neuronal communication. Furthermore, while most neurons show stereotypical response dynamics, some neurons exhibit versatile dynamics that are either stimulus specific or network-activity dependent. Notably, it is the collective dynamics of all responding neurons which provides valuable information that ultimately enhances stimulus identification, particularly when required to discriminate between closely-related stimuli. Together, these findings demonstrate how a compact and resource-limited chemosensory system can efficiently encode and discriminate a diverse range of chemical stimuli.
Functional diversity in the Hsp60 ofSulfolobus acidocaldarius: mosaic of Group I and Group II chaperonin
Authors: Bhakta Koustav , Roy Mousam , Samanta Shirsha , Ghosh Abhrajyoti 
Published: January 2024

AbstractExternal stress can disrupt protein homeostasis in organisms, necessitating the involvement of heat shock proteins (Hsps) to restore equilibrium and ensure survival. Unlike other organisms, the thermoacidophilic crenarchaeonSulfolobus acidocaldariuslacks Hsp100, Hsp90, and Hsp70, possessing only two small heat shock proteins (Hsp14 and Hsp20) and one group II chaperonin, Hsp60. This raises questions about how protein substrates are protected and transferred to Hsp60 for refolding without other chaperones. Our study focused on ATP-dependent Hsp60 inS. acidocaldarius, revealing its formation of oligomeric structures in the presence of ATP. While ATP hydrolysis is not essential for oligomer formation and lid closure, it is crucial for Hsp60’s chaperone activity, effectively folding stress-denatured substrate proteins by stabilizing their folded conformations. The mechanism involves hydrophobic recognition of unfolded substrates, encapsulating and releasing them in a more folded state. Negatively charged inner surface of the ring seems to be responsible for driving the folding of the substrate. Importantly, Hsp14 was found to transfer substrate proteins to Hsp60αβ, orchestrating their refolding into an active state. Beyond protein folding, Hsp60β protects the membrane under stress, contributing to maintaining membrane rigidity. Hsp60 exhibits nested cooperativity in ATPase activity, adapting to ATP concentration changes and interestingly Hsp60β and Hsp60αβ complex shows a mosaic behaviour during ATP hydrolysis belonging to both group I and group II chaperonin respectively. In conclusion, our study provides insights into the intricate mechanisms employed by Hsp60 inS. acidocaldariusto maintain protein homeostasis. It offers a comprehensive understanding of Hsp60’s role in the heat shock response pathway, shedding light on fundamental cellular processes in extremophilic archaea.
Endogenous glucocorticoids are required for normal macrophage activation and gastricHelicobacter pyloriimmunity
Authors: Khadka Stuti , Dziadowicz Sebastian A. , Xu Xiaojiang , Wang Lei , Hu Gangqing , Busada Jonathan T. 
Published: January 2024

AbstractGlucocorticoids are steroid hormones well-known for their potent anti-inflammatory effects. However, their immunomodulatory properties are multifaceted. Increasing evidence suggests that glucocorticoid signaling promotes effective immunity and that disruption of glucocorticoid signaling impairs immune function. In this study, we conditionally deleted the glucocorticoid receptor (GR) in the myeloid lineage using theLysM-Credriver (myGRKO). We examined the impact on macrophage activation and gastric immune responses toHelicobacter pylori, the best-known risk factor of gastric cancer. Our results indicate that compared to WT, GRKO macrophages exhibited higher expression of proinflammatory genes in steroid-free conditions. However, when challenged in vivo, GRKO macrophages exhibited aberrant chromatin landscapes and impaired proinflammatory gene expression profiles. Moreover, gastric colonization withHelicobacterrevealed impaired gastric immune responses and reduced T cell recruitment in myGRKO mice. As a result, myGRKO mice were protected from atrophic gastritis and pyloric metaplasia development. These results demonstrate a dual role for glucocorticoid signaling in preparing macrophages to respond to bacterial infection but limiting their pathogenic activation. In addition, our results support that macrophages are critical for gastric anti-Helicobacterimmunity.Graphical Abstract
Altering subjective time perception leads to correlated changes in neural activity and delay discounting impulsivity
Authors: Lee Sangil , Kable Joseph W. , Jung Wi Hoon 
Published: January 2024

AbstractSeveral accounts of delay discounting suggest subjective time perception as a contributing factor to individually varying discount rates. That is, one may seem impatient if their subjective perception of delay is longer than others’ perception of it. Here we build upon the behavioral and neural research on time perception, and we investigate the effects of manipulating an individual’s subjective time perception on their discount rates and neural activity. Using a novel time- counting task, we found that participants’ discount rates are affected by our manipulations of time perception and that neural activity also correlates with our manipulations in brain regions, such as the anterior insula and the superior temporal gyri, which have been implicated in time perception. We link these behavioral and neural findings together by showing that the degree of neural activity change in response to our manipulation is predictive of the degree of change in the participants’ discount rates.
Generation and benchmarking of a collection of hiPSC lines from Schizophrenia Patients with Diverse Clinical Profiles
Authors: Vecchi Elena Rita , Olmeda Claudia Vittoria , Bottai Daniele , Finelli Palma , Salavarria Marilyn Marlene Angulo , Gervasini Cristina , Mangiaterra Laura , Lombardi Francesco , Sanguineti Claudio , Onorati Marco , Conti Luciano , D’Agostino Armando 
Published: January 2024

ABSTRACTLimited therapeutic advancements in Schizophrenia (SCZ) depend on the heterogeneous nature of the disorder, impacting drug development and clinical trials that assume uniform therapy response, neglecting individual genetic and epigenomic variability. Disease modeling using human induced pluripotent stem cells (hiPSCs) is ideally suited for precision medicine, enabling individualized treatment approaches. Here, we describe the generation of patient-specific lines from somatic cells of SCZ individuals with well-defined diverse clinical trajectories using a Sendai virus-based reprogramming system. Karyotypically and CGH-array validated, the generated hiPSCs expressed diagnostic markers and demonstrated functional pluripotency. Converting these hiPSCs into neural progenitor cells enables the identification of aberrant cellular phenotypes associated with specific pathologically relevant neural phenotypes. This collection of hiPSC lines serves as a platform for developing therapeutic compounds targeting neural populations, potentially addressing early-stage disease alterations.
Live-cell fluorescence imaging and optogenetic control of PKA kinase activity in fission yeastSchizosaccharomyces pombe
Authors: Sakai Keiichiro , Aoki Kazuhiro , Goto Yuhei 
Published: January 2024

AbstractThe cAMP-PKA signaling pathway plays a crucial role in sensing and responding to nutrient availability in the fission yeastSchizosaccharomyces pombe.This pathway monitors external glucose levels to control cell growth and sexual differentiation. However, the temporal dynamics of the cAMP-PKA pathway in response to external stimuli remains unclear mainly due to the lack of tools to quantitatively visualize the activity of the pathway. Here, we report the development of the kinase translocation reporter (KTR)-based biosensor spPKA-KTR1.0, which allows us to measure the dynamics of PKA activity in fission yeast cells. The spPKA-KTR1.0 is derived from the transcription factor Rst2, which translocates from the nucleus to the cytoplasm upon PKA activation. We found that spPKA-KTR1.0 translocates between the nucleus and cytoplasm in a cAMP-PKA pathway-dependent manner, indicating that the spPKA-KTR1.0 is a reliable indicator of the PKA activity in fission yeast cells. In addition, we implemented a system that simultaneously visualizes and manipulates the cAMP-PKA signaling dynamics by introducing bPAC, a photoactivatable adenylate cyclase, in combination with spPKA-KTR1.0. This system offers an opportunity for investigating the role of the signaling dynamics of the cAMP-PKA pathway in fission yeast cells with higher temporal resolution.Take AwayspPKA-KTR1.0 allows visualization of PKA activity at the single-cell levelLive-cell imaging reveals the transient decrease in PKA activity after M-phaseOptogenetics allows simultaneous visualization and manipulation of PKA activity
A novel hypothesis-generating approach for detecting phenotypic associations using epigenetic data
Authors: Martin Florence Z. , Easey Kayleigh E. , Howe Laura D. , Fraser Abigail , Lawlor Deborah A. , Relton Caroline L. , Sharp Gemma C. 
Published: January 2024

AbstractBackgroundHypotheses about what phenotypes to include in causal analyses (that in turn can have clinical and policy implications) can be guided by hypothesis-free approaches, leveraging the epigenome for example. Materials & methods: Minimally adjusted epigenome-wide association studies (EWAS) using ALSPAC data were performed for example conditions, dysmenorrhea and heavy menstrual bleeding (HMB). Differentially methylated CpGs were searched in the EWAS Catalog and associated traits identified. Traits were compared between those with and without the example conditions in ALSPAC. Results: Seven CpG sites were associated with dysmenorrhea and two with HMB. Smoking and adverse childhood experience score were associated with both conditions in the hypothesis-testing phase. Conclusion: Hypothesis-generating EWAS can help identify associations for future analyses.Plain language summaryTo make a positive impact on policy and clinical practice, it is important that epidemiologists, those who study population health, can identify characteristics that might increase the risk of medical conditions. However, it can be difficult to know which associations should be investigated and decisions can often be biased by pre-formed opinions about what is relevant. In this study, we wanted to look for potential risk factors for dysmenorrhea (painful periods) and heavy menstrual bleeding (HMB) using a hypothesis-free approach (in other words, minimal adjustment for potential confounders), leveraging epigenetic data from a sub-sample of the Avon Longitudinal Study of Parents and Children (ALSPAC) and generating hypotheses about associations, then testing these hypotheses in the wider ALSPAC cohort. This meant looking for differentially methylated CpGs between those with and without the conditions of interest using an epigenome-wide association study (EWAS), seeing which phenotypes were associated with the CpGs in the EWAS Catalog, and testing these hypotheses in the ALSPAC cohort using measurements of each phenotype. For dysmenorrhea, we found seven differentially methylated CpGs and for HMB, we found two. These CpGs were associated with several phenotypes, which we could proxy in the wider ALSPAC cohort, creating hypotheses we tested using regression analyses. In the hypothesis-testing phase, we found that smoking and adverse childhood experience score were associated with dysmenorrhea and HMB. With this under-utilised approach, we can identify phenotypes that may be risk factors for under-studied conditions, that can be explored in other cohorts using analyses that can assess causality.Tweetable abstractLeveraging EWAS data can help identify novel potential risk factors for understudied conditions such as dysmenorrhea and heavy menstrual bleeding for future examination in causally motivated analyses: a proof-of-concept study in the Children of the 90’s cohort (ALSPAC)
Genomic adaptations to semi-aquatic and aquatic life in spiders
Authors: Fan Zheng , Wang Lu-Yu , Luo Bin , Ren Tian-Yu , Gao Jia-Xin , Liu Piao , Cheng Ling-Xin , Cai Yu-Jun , Tan Bing , Huang Qian , Deng Ming-Qin , Zuo Qing , Zhang Xiang-Yun , Lu Jin-Zhen , Sun Li-Na , Irfan Muhammad , Liu Ning , Tong Chao , Bai Ming , Zhang Zhi-Sheng 
Published: January 2024

AbstractSpiders have primarily adapted to terrestrial life, yet a number of species have made evolutionary transitions to marine and freshwater environments. While its physiological and behavioral adaptations have been characterized, the genetic basis of semi-aquatic and aquatic adaptation in spiders remains poorly understood. Here, we provide a high-quality, chromosome-level genome assembly for the aquatic spiderArgyroneta aquatica, alongside a reference transcriptome for the semi-aquatic spiderDesis martensi. We performed comparative genomes analyses of 22 spider species, including a unique aquatic spider, two semi-aquatic spiders and 19 terrestrial spider species, with a focus on those in the marronoid clade. By integrating morphological, phylogenomic, comparative genomic, transcriptomic, and metabolomic analyses, we explored the genomic adaptations of aquatic and semi-aquatic spiders. Phylogenomic analysis suggests that aquatic and semi-aquatic spiders have independently evolved from their terrestrial ancestors and represent divergent evolutionary routes We found hundreds of genes tend to experience relaxed selection, positive selection, and evidence of horizontal gene transfer (HGT) associated with the transition to aquatic and semi-aquatic life in spiders. These genes are associated with respiratory, osmoregulatory, fat metabolism and digestion, hypoxia, and thermal functions, putatively facilitate the adaptations to diverse underwater life. Altogether, our findings highlight the divergent evolutionary mechanisms enabling spiders to thrive in diverse aquatic environments, providing insights into the genomic basis of adaptations to semi-aquatic and aquatic habitats.
KaMRaT: a C++ toolkit fork-mer count matrix dimension reduction
Authors: Xue Haoliang , Gallopin Mélina , Marchet Camille , Nguyen Ha N. , Wang Yunfeng , Lainé Antoine , Bessiere Chloé , Gautheret Daniel 
Published: January 2024

AbstractSummaryKaMRaTis a program for processing largek-mer count tables extracted from high throughput sequencing data. Major functions include scoringk-mers based on count statistics, merging overlappingk-mers into longer contigs and selectingk-mers based on their presence in certain samples.KaMRaT‘s main application is the reference-free analysis of multi-sample and multi-condition datasets from RNA-seq, as well as ChiP-seq or ribo-seq experiments.KaMRaTenables the identification of condition-specific or differential sequences, irrespective of any gene or transcript annotation.Implementation and availabilityKaMRaTis implemented in C++. Source code and documentation are available viahttps://github.com/Transipedia/KaMRaT. Container images are available viahttps://hub.docker.com/r/xuehl/kamrat.