bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic requirements ofMycobacterium tuberculosisfor survival under pathogen-specific immunity
Authors: James Kimra S. , Jain Neharika , Witzl Kelly , Cicchetti Nico , Fortune Sarah M. , Ioerger Thomas R. , Martinot Amanda J. , Carey Allison F. 
Published: September 2024

ABSTRACTMycobacterium tuberculosis(Mtb), the etiologic agent of tuberculosis (TB), remains a persistent global health challenge due to the lack of an effective vaccine. The only licensed TB vaccine, Bacille Calmette-Guerin (BCG), is a live attenuated strain ofMycobacterium bovis, that protects young children from severe disease but fails to provide protection through adulthood. It is unclear why BCG-induced immunity provides incomplete protection despite inducing a robust CD4+ T cell response, a known critical correlate of protection against Mtb. We set out to interrogate mycobacterial determinants of vaccine escape using a functional genomics approach, TnSeq, to define mycobacterial genes required for survival in mice vaccinated with BCG, the live attenuated Mtb vaccine, ΔLprG, and in mice with Mtb immunity conferred by prior infection. We find that critical virulence genes associated with acute infection and exponential growth are less essential in hosts with adaptive immunity, including genes encoding the Esx-1 and Mce1 systems. Genetic requirements for Mtb growth in vaccinated and previously Mtb-infected hosts mirror the genetic requirements reported for bacteria grown underin vitroconditions that reflect aspects of the adaptive immune response as well as in mouse genetic backgrounds where bacterial growth is restricted. Across distinct immunization conditions, differences in genetic requirements between live attenuated vaccines and vaccination routes are observed, suggesting that different immunization strategies impose distinct bacterial stressors. Collectively, these data support the idea that Mtb requires genes that enable stress adaptation and growth arrest upon encountering the restrictive host environment induced by the adaptive immune response. We demonstrate that TnSeq can be used to understand the bacterial genetic requirements for survival in vaccinated hosts across pre-clinical live attenuated vaccines and therefore may be applied to other vaccine modalities. Understanding how Mtb survives in the setting of vaccine-induced immunity could uncover bacterial vulnerabilities to inform the development and prioritization of new vaccines or adjuvant therapies.
Cannabis smoke and oral Δ9THC enhance working memory in aged but not young adult subjects
Authors: Zequeira Sabrina , Gazarov Emely A , Guvenli Alara A , Berthold Erin C , Senetra Alexandria S , Febo Marcelo , Hiranita Takato , McMahon Lance R , Sharma Abhisheak , McCurdy Christopher R , Setlow Barry , Bizon Jennifer L 
Published: September 2024

ABSTRACTWith increased legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis use can impair cognition in young adults, it is critically important to understand how consumption interacts with the cognitive profile of aged individuals, who are already at increased risk of decline. The current study was designed to determine how cannabis influences multiple forms of cognition in young adult and aged rats of both sexes when delivered via two translationally-relevant routes of administration. Acute exposure to cannabis smoke enhanced prefrontal cortex-dependent working memory accuracy in aged males, but impaired accuracy in aged females, while having no effects in young adults of either sex. In contrast, the same cannabis smoke exposure regimen had minimal effects on a hippocampus-dependent trial-unique non-matching to location mnemonic task, irrespective of age or sex. In a second set of experiments, chronic oral consumption of Δ9-tetrahydrocannabinol (Δ9THC) enhanced working memory in aged rats of both sexes, while having no effects in young adults. In contrast, the same oral Δ9THC regimen did not affect spatial learning and memory in either age group. Minimal age differences were observed in Δ9THC pharmacokinetics with either route of administration. Together, these results show that cannabis and Δ9THC can attenuate working memory impairments that emerge in aging. While these enhancing effects do not extend to hippocampus-dependent cognition, cannabis does not appear to exacerbate age-associated impairments in this cognitive domain.
Reproducible Sex Differences in Personalized Functional Network Topography in Youth
Authors: Keller Arielle S. , Sun Kevin Y. , Francisco Ashley , Robinson Heather , Beydler Emily , Bassett Dani S. , Cieslak Matthew , Cui Zaixu , Davatzikos Christos , Fan Yong , Gardner Margaret , Kishton Rachel , Kornfield Sara L. , Larsen Bart , Li Hongming , Linder Isabella , Pines Adam , Pritschet Laura , Raznahan Armin , Roalf David R. , Seidlitz Jakob , Shafiei Golia , Shinohara Russell T. , Wolf Daniel H. , Alexander-Bloch Aaron , Satterthwaite Theodore D. , Shanmugan Sheila 
Published: September 2024

AbstractBackgroundA key step towards understanding psychiatric disorders that disproportionately impact female mental health is delineating the emergence of sex-specific patterns of brain organization at the critical transition from childhood to adolescence. Prior work suggests that individual differences in the spatial organization of functional brain networks across the cortex are associated with psychopathology and differ systematically by sex.AimsWe aimed to evaluate the impact of sex on the spatial organization of person-specific functional brain networks.MethodWe leveraged person-specific atlases of functional brain networks defined using non-negative matrix factorization in a sample ofn= 6437 youths from the Adolescent Brain Cognitive Development Study. Across independent discovery and replication samples, we used generalized additive models to uncover associations between sex and the spatial layout (“topography”) of personalized functional networks (PFNs). Next, we trained support vector machines to classify participants’ sex from multivariate patterns of PFN topography. Finally, we leveraged transcriptomic data from the Allen Human Brain Atlas to evaluate spatial correlations between sex differences in PFN topography and gene expression.ResultsSex differences in PFN topography were greatest in association networks including the fronto-parietal, ventral attention, and default mode networks. Machine learning models trained on participants’ PFNs were able to classify participant sex with high accuracy. Brain regions with the greatest sex differences in PFN topography were enriched in expression of X-linked genes as well as genes expressed in astrocytes and excitatory neurons.ConclusionsSex differences in PFN topography are robust, replicate across large-scale samples of youth, and are associated with expression patterns of X-linked genes. These results suggest a potential contributor to the female-biased risk in depressive and anxiety disorders that emerge at the transition from childhood to adolescence.
Metabolic reprogramming of immune cells in HIV infection and treatment
Authors: Xu Phoebe , Wu Di 
Published: September 2024

AbstractBACKGROUNDImmune cells undergo metabolic reprogramming, altering their energy production in response to HIV infection. During acute HIV infection, CD4+ T cells increase glycolysis to fuel viral replication and defense, but prolonged activation leads to immune exhaustion, with reduced T cell function and impaired pathogen elimination, contributing to AIDS progression. However, the details Metabolic dynamics of Immune Cells during HIV Infection (UT) and after receiving antiretroviral therapy (ART) remains unknown. Communication between Immune cells will be modified to response HIV infection, which can be mediated by metabolites. In this study, we deciphered Metabolic pathway dynamics of all Immune Cells by comparing UT and ART with seronegative controls (SN). Additionally, we investigate alteration of metabolite-mediated cell-cell communications in HIV Infection.METHODSSingle cell RNA sequencing (scRNA-seq) data of PBMC from SN, UT and ART were analyzed with KEGG Metabolic pathways by irGSEA and algorithm MEBOCOST to study cell-cell communications mediated by metabolites from sender cells and sensor proteins on receiver cells.RESULTSlots of differentially expressed Metabolic Pathways were identified for immune cells, including Energy Production and Utilization, Lipid Metabolism, Amino Acid Metabolism, Glycosylation and Glycan Biosynthesis and Oxidative Stress and Antioxidant Defense.CONCLUSIONSThe analysis highlights the intricate metabolic interplay between monocytes and other immune cells, reflecting their central role in orchestrating immune responses through metabolite exchange. These insights may open avenues for therapeutic interventions, targeting metabolic pathways to enhance immune function or inhibit pathogen survival.
Characterization of alternative mRNA splicing associated with tumor thrombus in clear-cell renal cell carcinoma
Authors: Cohen Zeev , Reinus Harel , Ben-Dov Iddo , Kalisky Tomer 
Published: September 2024

ABSTRACTApproximately 10% of Renal Cell Carcinoma (RCC) tumors form a thrombus that invades into nearby vasculature and is associated with lower survivability. However, the mechanisms driving tumor thrombus formation and progression are poorly understood. We therefore examined a publicly available RNAseq dataset of samples from RCC patients containing tumors with and without thrombi, as well as associated normal kidney tissues, and compared them. Using cell deconvolution, we found indications that kidney tumors and thrombi are associated with loss of mature kidney-specific cell types and gain of proliferative characteristics. Moreover, we identified a set of transcripts that are alternatively spliced between tumors with and without thrombi. Using motif enrichment analysis for known RNA binding proteins we found putative splicing regulators that are presumably associated with thrombus formation. We believe that this study will assist in unraveling cellular and molecular mechanisms of tumor progression and thrombus formation in RCC.
Functional traits predict outcomes of current and novel competition under warmer climate
Authors: Lyu Shengman , Alexander Jake M. 
Published: September 2024

AbstractFunctional traits offer a potential avenue to generalize and forecast the impacts of changing competition on plant communities, including changing outcomes of competition among species that currently interact (current competition) or that will interact in the future following range shifts (novel competition). However, it remains unclear how well traits explain variation in the outcomes of current and novel competition, as well as the underlying processes determining coexistence or competitive exclusion, under changing climate. Here, we conducted a field experiment in which pairs of high and low-elevation species interacted in three sites across an elevation gradient in the Swiss Alps. For each species pair, we quantified the population-level outcomes of competition (invasion growth rates), relative fitness differences and niche overlap and related these to 15 functional traits that were measured in each site. Most traits were significantly associated with invasion growth rates at the low elevation, where species had greater relative fitness differences, but these associations were much weaker towards higher elevations. This appears to be because traits, particularly those associated with light competition, captured species’ relative fitness differences at lower elevations, but not at the high elevation site. Greater relative fitness differences towards lower elevations suggest that climate warming may increase the likelihood of competitive exclusion of species that are poor competitors for light. In addition, novel competitors tended to show greater niche overlap than current competitors, leading to stronger overall competitive effects. But in general, trait differences predicted competitive outcomes of novel and current competitors similarly well, suggesting that traits can be used to predict interactions between species that do not yet interact. Our study reinforces the importance of considering changing interactions for predicting species responses to climate change and provides experimental evidence supporting the usefulness of functional trait differences in forecasting the impacts of future plant interactions under changing climate.
Viral epidemic potential is not uniformly distributed across the bat phylogeny
Authors: Cummings Caroline A. , Vicente-Santos Amanda , Carlson Colin J. , Becker Daniel J. 
Published: September 2024

AbstractCharacterizing host–virus associations is critical due to the rising frequency of emerging infectious diseases originating from wildlife. Past analyses have evaluated zoonotic risk as binary, but virulence and transmissibility can vary dramatically. Recent work suggests bats harbor more viruses with high virulence in humans than other taxa. However, it remains unknown whether all bats harbor viruses of equal zoonotic potential. We used phylogenetic factorization to flexibly identify clades of mammals (at any taxonomic level) associated with low or high viral epidemic potential, and found virulence and transmissibility only cluster within bat subclades, often among cosmopolitan families. Mapping the geographic distributions of these bat clades with spatial data on anthropogenic footprint suggests high zoonotic risk in coastal South America, Southeast Asia, and equatorial Africa. Our results deepen understanding of the host– virus network and identify clades to prioritize for viral surveillance, risk mitigation, and future studies characterizing mechanisms of viral tolerance.
A Collagen Triple Helix without the Super Helical Twist
Authors: Kreutzberger Mark A. B. , Yu Le Tracy , Hancu Maria C. , Purdy Michael D. , Osinski Tomasz , Kasson Peter , Egelman Edward H. , Hartgerink Jeffrey D. 
Published: September 2024

AbstractCollagens are ubiquitous in biology functioning as the backbone of the extracellular matrix, forming the primary structural components of key immune system complexes, and fulfilling numerous other structural roles in a variety of systems. Despite this, there is limited understanding of how triple helices, the basic collagen structural units, pack into collagenous assemblies. Here we use a peptide self-assembly system to design collagenous assemblies based on the C1q collagen-like region. Using cryo-EM we solve a structure of one assembly to 3.5 Å resolution and build an atomic model. From this, we identify a triple helix conformation with no superhelical twist, starkly in contrast to the canonical right-handed triple helix. This non-twisting region allows for unique hydroxyproline stacking between adjacent triple helices and also results in the formation of an exposed cavity with rings of hydrophobic amino acids packed symmetrically. We find no precedent for such an arrangement of collagen triple helices and have designed mutant assemblies to probe key stabilizing amino acid interactions in the complex. The mutations behave as predicted by our atomic model. Our findings, combined with the extremely limited experimental structural data on triple helix packing in the literature, suggest that collagen and collagen-like assemblies may adopt a far more varied conformational landscape than previously appreciated. We hypothesize that this is particularly likely adjacent to the termini of these helices and at discontinuities to the required Xaa-Yaa-Gly repeating primary sequence; a discontinuity found in the majority of this class of proteins and in many collagen-associated diseases.
Estimating sampling and laboratory capacity for a simulated African swine fever outbreak in the United States
Authors: Galvis Jason A. , Satici Muhammed Y. , Sykes Abagael L. , O’Hara Kathleen C. , Rochette Lisa , Roberts David , Machado Gustavo 
Published: September 2024

AbstractThe introduction of African swine fever virus (ASFV) into uninfected countries can impact economic and animal welfare. Rapid detection and control of the outbreak contribute to successful eradication and promote business continuity. We developed a model to determine the number of samples, sample collectors, laboratory capacity, and processing times following an ASFV introduction into the U.S. We simulated the spread of ASFV in one densely populated swine region, generating a median of 27 (range = 1-68) outbreaks in 150 days, resulting 616 (range = 1-15,011) sampling events with a total of 3,068 barns (range = 7-69,118) sampled. We calculated the total sample collectors needed, considering daily working hours, sampling and driving time, and laboratory capabilities with and without blood sample pooling. Samples included 31 blood samples and five oral fluid samples per barn, which equal 84,830 (range = 52-2,066,831) and 14,195 (range = 10-345,590) blood and oral fluid samples, respectively. The median number of sample collectors needed to prevent sampling delay varied from 136 to 367 and, in the worst epidemic scenarios, from 833 to 3,115. Notably, excluding downtime–which prevented the sampler from visiting additional farms for 24 or 72 hours–reduced the number of sample collectors needed between 28% and 75%, while switching from blood to oral fluid samples reduced this number between 47% and 75%. At a laboratory processing daily capacity of 1,000 samples, the median days for sample processing without pooling were 92 days, with a maximum of 5.7 years. We demonstrated a need to redistribute 10,062 (range = 2-67,940) unprocessed samples daily to other laboratories to prevent processing delays. Our study addresses the challenge of efficiently organizing resources for managing a potential ASFV outbreak, providing information about the number of sample collectors and laboratory capacity needed for one densely populated swine region in the U.S.
Enzymatic protein fusions with 100% product yield
Authors: Fuchs Adrian C. D. 
Published: September 2024

SummaryThe protein ligase Connectase can be used to fuse proteins to small molecules, solid carriers, or other proteins. Compared to other protein ligases, it offers greater substrate specificity, higher catalytic efficiency, and catalyzes no side reactions. However, its reaction is reversible, resulting in only 50% fusion product from two equally abundant educts. Here, we present a simple method to reliably obtain 100% fusion product in 1:1 conjugation reactions. This method is efficient for protein-protein or protein-peptide fusions at the N-or C-termini. It enables the generation of defined and completely labeled antibody conjugates with one fusion partner on each chain. The reaction requires short incubation times with small amounts of enzyme and is effective even at low substrate concentrations and at low temperatures. With these characteristics, it presents a valuable new tool for bioengineering.
Connectivity in the Dorsal Visual Stream is Enhanced in Action Video Game Players
Authors: Cahill Kyle , Jordan Timothy , Dhamala Mukesh 
Published: September 2024

ABSTRACTAction video games foster competitive environments that demand rapid spatial navigation and decision-making. Action video gamers often exhibit faster response times and slightly improved accuracy in vision-based sensorimotor tasks. However, the underlying functional and structural changes in the two visual streams of the brain that may be contributing to these cognitive improvements have been unclear. Using functional and diffusion MRI data, this study investigated the differences in connectivity between gamers who play action video games and nongamers in the dorsal and ventral visual streams. We found that action video gamers have enhanced functional and structural connectivity, especially in the dorsal visual stream. Specifically, there is heightened functional connectivity—both undirected and directed—between the left Superior Occipital Gyrus and the left Superior Parietal Lobule during a moving-dots discrimination decision-making task. This increased connectivity correlates with response time in gamers. The structural connectivity, as quantified by diffusion fractional anisotropy and quantitative anisotropy measures of the axonal fiber pathways between the same regions was also enhanced for gamers compared to nongamers. These findings provide valuable insights into how action video gaming can induce targeted neuroplastic changes, enhancing structural and functional connectivity between specific brain regions in the visual processing pathways. These connectivity changes in the dorsal visual stream underpin the superior performance of action video gamers compared to non-gamers in tasks requiring rapid and accurate vision-based decision-making.GRAPHICAL ABSTRACTImpact StatementUnderstanding the neural mechanisms underlying how observed cognitive alterations due to video game playing are achieved has potential implications for future cognitive training, rehabilitation, and education. The structural and functional MRI analysis in this study provides a quantitative basis by which the underlying neural connectivity changes due to video game playing in the visual streams may be assessed and linked to observed behavioral differences. These methods are extendible and provide insight into underlying neural network enhancements associated with improved cognitive performance due to video game playing. The findings of this study support enhanced functional and structural connectivity in the dorsal visual stream among gamers due to video game playing in the behavioral paradigm of vision-based sensorimotor decision-making. Functional connectivity measures that were considered were significantly correlated with the participants’ response times.