bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urban living can rescue Darwin’s finches from the lethal effects of invasive vampire flies
Authors: Knutie Sarah A. , Webster Cynthia N. , Vaziri Grace J. , Albert Lauren , Harvey Johanna A. , LaRue Michelle , Verrett Taylor B. , Soldo Alexandria , Koop Jennifer A.H. , Chaves Jaime A. , Wegrzyn Jill L. 
Published: March 2023

AbstractHuman activity changes multiple factors in the environment, which can have additive or neutralizing effects on organisms. However, few studies have explored the causal effects of multiple anthropogenic factors, such as urbanization and invasive species, on animals, and the mechanisms that mediate these interactions. This study examines the influence of urbanization on the detrimental effect of invasive avian vampire flies (Philornis downsi) on endemic Darwin’s finches in the Galápagos Islands. We experimentally manipulated nest fly abundance in an urban and non-urban area and then characterized nestling health, survival, diet, and gene expression patterns related to host defense. Survival of fumigated nestlings from urban and non-urban nests did not differ significantly. However, sham-fumigated, non-urban nestlings lost more blood and few nestlings survived compared to urban nestlings. Stable isotopic values (δ15N) from urban nestling feces were higher than non-urban nestlings, suggesting that urban nestlings are consuming more protein. δ15N values correlated negatively with parasite abundance, which suggests that diet might influence host defenses (e.g., tolerance and resistance). Parasitized urban nestlings differentially expressed genes within pathways associated with red blood cell production (tolerance) and pro-inflammatory response (innate immunological resistance), compared to sham-fumigated non-urban nestlings. In contrast, sham-fumigated non-urban nestlings differentially expressed genes within pathways associated with immunoglobulin production (adaptive immunological resistance). Our results suggest that urban nestlings are investing more in pro-inflammatory responses to resist parasites, but also recovering more blood cells to tolerate blood loss. Although non-urban nestlings are mounting an adaptive immune response, it is likely a last effort by the immune system rather than an effective defense against avian vampire flies since few nestlings survived.
Cytotoxic CD4+T cells eliminate senescent cells by targeting cytomegalovirus antigen
Authors: Hasegawa Tatsuya , Oka Tomonori , Son Heehwa G. , Oliver-García Valeria S. , Azin Marjan , Eisenhaure Thomas M. , Lieb David J. , Hacohen Nir , Demehri Shadmehr 
Published: March 2023

ABSTRACTSenescent cell accumulation has been implicated in the pathogenesis of aging-associated diseases including cancer. The mechanism that prevents the accumulation of senescent cells in aging human organs is unclear. Here, we demonstrate that a virus-immune axis controls the senescent fibroblast accumulation in the human skin. Senescent fibroblasts increased in old compared with young skin. However, they did not increase with advancing age in the elderly. Increased CXCL9 and cytotoxic CD4+T cell (CD4 CTL) recruitment were significantly associated with reduced senescent fibroblasts in the old skin. Senescent fibroblasts expressed human leukocyte antigen class II (HLA-II) and human cytomegalovirus glycoprotein B (HCMV-gB), becoming direct CD4 CTL targets. Skin-resident CD4 CTL eliminated HCMV-gB+senescent fibroblasts in an HLA-II-dependent manner, and HCMV-gB activated CD4 CTL from the human skin. Collectively, our findings demonstrate HCMV reactivation in senescent cells, which can be directly eliminated by CD4 CTL through the recognition of the HCMV-gB antigen.
Modulation of locus coeruleus neurons and strong release of noradrenaline during acute hippocampal seizures in rats
Authors: Larsen Lars Emil , Caestecker Sielke , Stevens Latoya , van Mierlo Pieter , Carrette Evelien , Boon Paul , Vonck Kristl , Raedt Robrecht 
Published: March 2023

AbstractThe locus coeruleus (LC), a brainstem nucleus, is the sole source of noradrenaline in the neocortex, hippocampus and cerebellum. Noradrenaline is a powerful neuromodulator involved in the regulation of excitability and plasticity of large-scale brain networks. In this study, we assessed the activity of locus coeruleus neurons and changes in noradrenergic transmission during acute hippocampal seizures evoked with perforant path stimulation. LC neurons were recorded in anesthetized rats using a multichannel electrophysiology probe and were identified based on electrophysiological characteristics or optogenetic tagging. The majority of LC neurons (55%) were inhibited during seizures, while only a subset of LC neurons (28%) was excited during seizures. Topographic analysis of multi-unit activity showed anatomical separation of neurons that were excited and inhibited during seizures. Changes in hippocampal noradrenaline transmission during seizures were assessed using a fluorescent biosensor for noradrenaline, GRABNE2m, in combination with fiber photometry in both anesthetized and awake rats. Our results indicate that acute electrically evoked hippocampal seizures are associated with strong changes in LC unit activity and strong and consistent time-locked release of noradrenaline. Understanding the role of mass release of noradrenaline during hippocampal seizures is likely to be important to understand seizure pathophysiology.
Challenging popular belief, mosquito larvae breathe underwater
Authors: Alvarez-Costa Agustin , Leonardi Maria Soledad , Giraud Silvère , Schilman Pablo E. , Lazzari Claudio R. 
Published: March 2023

AbstractIt is taken for granted that immature mosquito only breathe atmospheric air through their siphons. However, there is no quantitative study that demonstrated it. We analysed the survival of the last instar larvae ofAedes aegyptifully submerged at different temperatures, and measured oxygen consumption from air and dissolved in water, of larvae and pupae of this species under different conditions. Results revealed that under water, larvae survived much longer than expected, reaching 50% mortality only after 58, 10, and 5 days at 15°, 25° and 35°C, respectively. Interestingly, whereas we registered moults to pupae in larvae with access to air, individuals kept submerged never moulted. When remaining at the water surface, larvae obtained 12.72% of O2from the water, while pupae only 5.32%. When completely submerged, larvae consumed less oxygen than in contact with the surface, but enough for surviving, while pupae did not. At both media, temperature affected larvae respiration rate, with relatively close Q10values. In the related species,Ae. albopictus, a similar pattern of O2consumption were observed. Larvae got 12.14% of their oxygen from the water. Interestingly, no significant differences in total O2consumption were found between water O2consumption, whenAe. albopictuslarvae were submerged, or when they also have access to air (dual O2consumption). Our findings not only challenge the classical idea that mosquito larvae only breathe atmospheric O2, but also force us to reconsider the potential effectiveness of control methods based on asphyxiating larvae by detaching from water surface.Summary statementWe present the first quantitative analysis of mosquito larvae respiration in air and water, unravelling the unknown capacity of larvae of the most cosmopolitan disease vector of breathing underwater.
Cryo-electron tomography sheds light on the elastic nature of theTrypanosoma bruceitripartite attachment complex
Authors: Bregy Irina , Radecke Julika , Noga Akira , van den Hoek Hugo , Kern Mara , Haenni Beat , Engel Benjamin D. , Siebert C. Alistair , Ishikawa Takashi , Zuber Benoît , Ochsenreiter Torsten 
Published: March 2023

AbstractIn contrast to many eukaryotic organisms, trypanosomes only contain a single mitochondrion per cell. Within that singular mitochondrion, the protist carries a single mitochondrial genome that consists of a complex DNA network, the kinetoplast DNA (kDNA). Segregation of the replicated kDNA is coordinated by the basal body of the cell’s single flagellum. The tripartite attachment complex (TAC) forms a physical connection between the proximal end of the basal body and the kDNA. This allows anchoring of the kDNA throughout the cell cycle and couples kDNA segregation with the separation of the basal bodies prior to cell division. Over the past years, several components of the TAC have been identified. To shed light on the structure of the cytoplasmic part of the TAC (known as the exclusion zone), we performed cryo-electron tomography on whole cells. This allowed us to acquire three-dimensional high-resolution images of the exclusion zonein situ. We observed that the exclusion zone filaments offer great mechanical flexibility for basal body movement. We measured the dimensions of the individual structural elements of the area, as well as the overall orientation and positioning of the basal bodies towards the mitochondrial kDNA pocket. Using a combination of experimental data and modelling, we generated a structural model of the exclusion zone protein p197. Our findings suggest that the majority of p197 consists of a string of spectrin-like repeats. We propose that these structural units provide the architecture of a molecular spring and that they are required in the TAC to withstand the mechanical forces generated through basal body repositioning events during kDNA segregation and motility of the organism.
Variation in female-biased sexual size dimorphism of Northern Pike (Esox lucius) associated with environment and life history
Authors: Kennedy P.J. , Rennie M.D. 
Published: March 2023

ABSTRACTBackgroundSexual size dimorphism (SSD) is a widespread phenomenon in the animal world resulting from differential selection on the sexes. The Northern Pike (Esox lucius) is a freshwater apex predatory fish species that exhibits female-biased SSD, but the degree to which SSD varies among populations and what variables might dictate variation in SSD in this species remain poorly understood.AimWe sought to quantify the degree of variation in SSD among Northern Pike populations across a large portion of their North American range, as well as evaluate associations between the magnitude of SSD in Northern Pike populations with environmental variables and life history traits of populations.MethodsWe quantified SSD in 102 populations of Northern Pike across the province of Ontario, Canada, using a standardized gillnetting database. We further investigated the degree to which both environmental variables (Cisco abundance as catch-per-unit-effort, lake surface area, and latitude) and Northern Pike life-history traits (early growth and mortality rates) explained variation in female-biased SSD using linear models.ResultsFemale-biased SSD in mean weight of Northern Pike increased with increasing Cisco (Coregonus artedi) abundance, and the difference in female and male mean age increased with increasing latitude. Furthermore, SSD was greater in populations with lower female mortality and early growth rates.ConclusionThis study indicates that slow-growing, long-lived populations of Northern Pike should exhibit greater female-biased SSD, and that these conditions may be facilitated by the availability of large, energy-dense prey and cooler temperatures at northern latitudes.
Antigenic strain diversity predicts different biogeographic patterns of maintenance and decline of anti-malarial drug resistance
Authors: He Qixin , Chaillet John K. , Labbé Frédéric 
Published: March 2023

AbstractThe establishment and spread of anti-malarial drug resistance vary drastically across different biogeographic regions. Though most infections occur in Sub-Saharan Africa, resistant strains often emerge in low-transmission regions. Existing models on resistance evolution lack consensus on the relationship between transmission intensity and drug resistance, possibly due to overlooking the feedback between antigenic diversity, host immunity, and selection for resistance. To address this, we developed a novel compartmental model that tracks sensitive and resistant parasite strains, as well as the host dynamics of generalized and antigen-specific immunity. Our results show a negative correlation between parasite prevalence and resistance frequency, regardless of resistance cost or efficacy. Validation using chloroquine-resistant marker data supports this trend. Post discontinuation of drugs, resistance remains high in low-diversity, low-transmission regions, while it steadily decreases in high-diversity, high-transmission regions. Our study underscores the critical role of malaria strain diversity in the biogeographic patterns of resistance evolution.
A molecularly defined and spatially resolved cell atlas of the whole mouse brain
Authors: Zhang Meng , Pan Xingjie , Jung Won , Halpern Aaron , Eichhorn Stephen W. , Lei Zhiyun , Cohen Limor , Smith Kimberly A. , Tasic Bosiljka , Yao Zizhen , Zeng Hongkui , Zhuang Xiaowei 
Published: March 2023

AbstractIn mammalian brains, tens of millions to billions of cells form complex interaction networks to enable a wide range of functions. The enormous diversity and intricate organization of cells in the brain have so far hindered our understanding of the molecular and cellular basis of its functions. Recent advances in spatially resolved single-cell transcriptomics have allowed systematic mapping of the spatial organization of molecularly defined cell types in complex tissues1–3. However, these approaches have only been applied to a few brain regions1–11and a comprehensive cell atlas of the whole brain is still missing. Here, we imaged a panel of >1,100 genes in ∼8 million cells across the entire adult mouse brain using multiplexed error-robust fluorescence in situ hybridization (MERFISH)12and performed spatially resolved, single-cell expression profiling at the whole-transcriptome scale by integrating MERFISH and single-cell RNA-sequencing (scRNA-seq) data. Using this approach, we generated a comprehensive cell atlas of >5,000 transcriptionally distinct cell clusters, belonging to ∼300 major cell types, in the whole mouse brain with high molecular and spatial resolution. Registration of the MERFISH images to the common coordinate framework (CCF) of the mouse brain further allowed systematic quantifications of the cell composition and organization in individual brain regions defined in the CCF. We further identified spatial modules characterized by distinct cell-type compositions and spatial gradients featuring gradual changes in the gene-expression profiles of cells. Finally, this high-resolution spatial map of cells, with a transcriptome-wide expression profile associated with each cell, allowed us to infer cell-type-specific interactions between several hundred pairs of molecularly defined cell types and predict potential molecular (ligand-receptor) basis and functional implications of these cell-cell interactions. These results provide rich insights into the molecular and cellular architecture of the brain and a valuable resource for future functional investigations of neural circuits and their dysfunction in diseases.
Integration of Avidity and Differentiation is enabled by CD8+T-cell sensing of IFN-γ
Authors: Uhl Lion F.K. , Cai Han , Mahale Jagdish N. , MacLean Andrew J. , Mazet Julie M. , He Alexander J. , Lau Doreen , Elliott Tim , Gerard Audrey 
Published: March 2023

AbstractThe most effective responses to intracellular pathogens have a breadth of T-cell clones with different affinities for their cognate peptide, and a diversity of functional phenotypes, from effector to long-lived memory cells. While high- and low-affinity T-cells are inherently skewed towards becoming effector and memory, respectively, overall, both functional subsets exploit a wide range of affinities. How the breadth of affinities and functionalities are coordinated is therefore unclear. In this study, we provide evidence that direct sensing of the cytokine IFN-γ by CD8+T-cells is a factor controlling the integration of T-cell affinity and differentiation during infection. IFN-γ increases the expansion of low-affinity T-cells, allowing them to overcome the selective advantage of high-affinity T-cells. Concomitantly, IFN-γ reinforces high-affinity T-cell entry into the memory pool. As a result, direct IFN-γ sensing by CD8+T-cells increases the avidity of the memory response. This comes at the expense of the primary T-cell response, for which IFN-γ decreases the avidity, leading to sub-optimum immunity to infection. IFN-γ sensing by CD8+T-cells is paracrine, provided by a distinct subset of CD8+T-cells called Virtual Memory T-cells, an antigen inexperienced subset that harbors memory features. Overall, we propose that IFN-γ and Virtual Memory T-cells fulfil a critical immunoregulatory role by enabling the coordination of T-cell avidity and fate.
Accurate modeling of peptide-MHC structures with AlphaFold
Authors: Mikhaylov Victor , Levine Arnold J. 
Published: March 2023

SummaryMajor histocompatibility complex (MHC) proteins present peptides on the cell surface for T-cell surveillance. Reliablein silicoprediction of which peptides would be presented and which T-cell receptors would recognize them is an important problem in structural immunology. Here, we introduce an AlphaFold-based pipeline for predicting the three-dimensional structures of peptide-MHC complexes for class I and class II MHC molecules. Our method demonstrates high accuracy, outperforming existing tools in class I modeling precision and class II peptide register prediction. We explore applications of this method towards improving peptide-MHC binding prediction.
SAKit: an all-in-one analysis pipeline for identifying novel protein caused by variant events at genomic and transcriptic level
Authors: Li Yan , Wang Boran , Wu Zengding , Xu Shi , Cui Fenglei , Fei Caiyi , Sun Qiang 
Published: March 2023

AbstractSummaryGenetic modifications that cause pivotal protein inactivation or abnormal activation may lead to cell signaling pathway change or even dysfunction, resulting in cancer and other diseases. In turn, dysfunction will further produce “novel proteins” that do not exist in the canonical human proteome. Identification of novel proteins is meaningful for identifying promising drug targets and developing new therapies. In recent years, several tools have been developed for identifying DNA or RNA variants with the extensive application of nucleotide sequencing technology. However, these tools mainly focus on point mutation and have limited performance in identifying large-scale variants as well as the integration of mutations. Here we developed a hybridSequencingAnalysis bioinformatic pipeline by integrating all relevant detectionKits(SAKit): this pipeline fully integrates all variants at the genomic and transcriptomic level that may lead to the production of novel proteins defined as proteins with novel sequences compare to all reference sequences by comprehensively analyzing the long and short reads. The analysis results of SAKit demonstrate that large-scale mutations have more contribution to the production of novel proteins than point mutations, and long-read sequencing has more advantages in large-scale mutation detection.Availability and implementationSAKit is freely available on docker image (https://hub.docker.com/repository/docker/therarna/sakit), which is mainly implemented within a Snakemake framework in Python language.
Fear-conditioning to unpredictable threats reveals sex differences in rat fear-potentiated startle (FPS)
Authors: Olivera-Pasilio Valentina , Dabrowska Joanna 
Published: March 2023

AbstractFear-potentiated startle (FPS) has been widely used to study fear processing in humans and rodents. Human studies have shown higher startle amplitudes and exaggerated fear reactivity to unpredictable vs. predictable threats in individuals suffering from post-traumatic stress disorder (PTSD). Although human FPS studies often use both sexes, a surprisingly limited number of rodent FPS studies use females. Here we investigate the effects of signal-threat contingency, signal-threat order and threat predictability on FPS in both sexes. We use a classic fear-conditioning protocol (100% contingency of cue and shock pairings, with forward conditioning such that the cue co-terminates with the shock) and compare it to modified fear-conditioning protocols (70% contingency; backward conditioning; or cue and shock unpaired). Although there are no sex differences in the startle amplitudes when corrected for body weight, females demonstrate higher shock reactivity during fear-conditioning. Both sexes demonstrate comparable levels of cued, non-cued, and contextual fear in the classic FPS but females show reduced fear discrimination vs. males. Fear-conditioning with 70% contingency or backward order (cue co-starts with shock) induces similar levels of cued, non-cued, and contextual fear in both sexes but they differ in contextual fear extinction. Lastly, a prominent sex difference is uncovered following unpredictable fear-conditioning protocol (cue and shock un-paired), with females showing significantly higher startle overall during the FPS recall, regardless of trial type, and higher contextual fear than males. This striking sex difference in processing unpredictable threats in rodent FPS might help to understand the mechanisms underlying higher incidence of PTSD in women.HighlightsMale and female rats have comparable startle amplitudes when corrected for body weightFemale rats show higher foot-shock reactivity than males during fear-conditioningFemale rats show reduced fear discrimination vs. males in the classic FPSReversed signal-threat order increases contextual fear in both sexesExposure to unpredictable threats increases startle in general and contextual fear only in females