bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can social interactions rescue “lost” behavioural defences in an allopatric cuckoo host?
Authors: Tolman Deryk , Ronkä Katja , Kluen Edward , Campobello Daniela , Thorogood Rose 
Published: January 2024

ABSTRACTSocial information use by cuckoo-hosts provides an excellent example of how social interactions within species can influence selection on another. Neighbours observe each other’s mobbing behaviour towards cuckoos, and then adjust costly defences back at their own nest in response. This may even allow naïve juveniles to ‘learn’ to recognise cuckoos, suggesting that ‘social responsiveness’ must play a key part in determining how hosts respond to changing rates of brood parasitism. However, if the ‘cultural memory’ of cuckoos is lost, can this plasticity in defences be rescued? This is fundamental for cuckoo-host coevolution, as the rates at which host defences are lost, gained, or retained determines evolutionary dynamics. Using populations of reed warblers at the northern- and southernmost extents of their range, we designed a field experiment to test whether populations allopatric to cuckoos (i) still recognise cuckoos as a threat, (ii) respond to social cues to upregulate defences, and (iii) vary in their strength of social responsiveness. We found defences and social responsiveness to be weaker in the south, where there is a much longer history of allopatry. In the north, only birds that retained recognition of cuckoos showed social responsiveness: social information about cuckoos did not increase hosts’ propensity to attack (whereas it doubled in the range core), but it did increase the strength of mobbing in the 30% of birds that recognised the cuckoo at the northern range front. Most importantly, however, experimental cuckoo eggs remained in the nest, whereas in previous experiments elsewhere the same social information increased egg rejection ten-fold. This suggests that social responsiveness is more limited at the range edges, under relaxed selection, and this would incur little immediate cost to cuckoos’ fitness if they (re)invade. Our study provides a rare example of geographic variation in social information use and highlights how current range expansions may influence the outcome of future species interactions.
GVRP: Genome Variant Refinement Pipeline for variant analysis in non-human species using machine learning
Authors: Choi Jeonghoon , Zhou Bo , Song Giltae 
Published: January 2024

AbstractMany investigations of human disease require model systems such as non-human primates and their associated genome analyses. While DeepVariant excels in calling human genetic variations, its reliance on calibrating against known variants from previous population studies poses challenges for non-human species.To address this limitation, we introduce the Genome Variant Refinement Pipeline (GVRP), employing a machine learning-based approach to refine variant calls in non-human species. Rather than training separate variant callers for each species, we employ a machine learning model to accurately identify variations and filter out false positives from DeepVariant.In GVRP, we omit certain DeepVariant preprocessing steps and leverage the ground-truth Genome In A Bottle (GIAB) variant calls to train the machine learning model for non-human species genome variant refinement. We anticipate that GVRP will significantly expedite genome variation studies for non-human species,.
Investigation of the heterogeneity of cancer cells using single cell Ca2+profiling
Authors: Bura Amélie E. , Caussette Camille , Guéguinou Maxime , Bellanger Dorine , Robert Alison , Cancel Mathilde , Lacouette-Rata Margot , Fromont Gaëlle , Vandier Christophe , Mahéo Karine , Brouard Thierry , Crottès David 
Published: January 2024

AbstractCalcium (Ca2+) is an essential and ubiquitous second messenger that controls numerous cellular functions. The regulation of intracellular Ca2+oscillations defines a Ca2+signature that is representative of the cellular identity and the phenotype of a cell. In cancers, aberrant Ca2+fluxes have been associated with characteristics such as migration, proliferation or resistance to chemotherapy. However, it remains unclear whether cancer cells have specific Ca2+signatures that are representative of their oncogenic properties. To reveal the existence of oncogenic Ca2+signatures, we develop a method combining single cell calcium imaging and unsupervised and supervised machine learning approaches. Briefly, we generated a database of 27,439 single-cell agonist-induced Ca2+responses obtained from 16 prostate and colon cancer cell lines. Graph-based unsupervised clustering was used to define and compare Ca2+signatures of cancer cell lines. A supervised neural network model trained on the collection of agonist-induced Ca2+responses successfully identify individual cancer cells and predicted some of their characteristics. We extend these methods to observe Ca2+signatures of docetaxel-resistant cancer cells and in a co-culture model mimicking the interaction of cancer cells with cancer-associated fibroblasts. Our models successfully highlight subtle changes in those Ca2+signatures and are able to distinguish individual cancer cells from fibroblasts and predict their sensitivity to Docetaxel. Taken together, this study provides a proof of concept that cancer cells can be defined by their Ca2+signature and conversely that Ca2+signaling can serve as a predictor of cancer cell characteristics.
Genome scale CRISPR screens identify actin capping proteins as key modulators of therapeutic responses to radiation and immunotherapy
Authors: Verma Nipun , Renauer Paul A. , Dong Chuanpeng , Xin Shan , Lin Qianqian , Zhang Feifei , Glazer Peter M. , Chen Sidi 
Published: January 2024

AbstractRadiotherapy (RT), is a fundamental treatment for malignant tumors and is used in over half of cancer patients. As radiation can promote anti-tumor immune effects, a promising therapeutic strategy is to combine radiation with immune checkpoint inhibitors (ICIs). However, the genetic determinants that impact therapeutic response in the context of combination therapy with radiation and ICI have not been systematically investigated. To unbiasedly identify the tumor intrinsic genetic factors governing such responses, we perform a set of genome-scale CRISPR screens in melanoma cells for cancer survival in response to low-dose genotoxic radiation treatment, in the context of CD8 T cell co-culture and with anti-PD1 checkpoint blockade antibody. Two actin capping proteins,Capza3andCapg, emerge as top hits that upon inactivation promote the survival of melanoma cells in such settings.Capza3andCapgknockouts (KOs) in mouse and human cancer cells display persistent DNA damage due to impaired homology directed repair (HDR); along with increased radiation, chemotherapy, and DNA repair inhibitor sensitivity. However, when cancer cells with these genes inactivated were exposed to sublethal radiation, inactivation of such actin capping protein promotes activation of the STING pathway, induction of inhibitoryCEACAM1ligand expression and resistance to CD8 T cell killing. Patient cancer genomics analysis reveals an increased mutational burden in patients with inactivating mutations inCAPGand/orCAPZA3, at levels comparable to other HDR associated genes. There is also a positive correlation betweenCAPGexpression and activation of immune related pathways and CD8 T cell tumor infiltration. Our results unveil the critical roles of actin binding proteins for efficient HDR within cancer cells and demonstrate a previously unrecognized regulatory mechanism of therapeutic response to radiation and immunotherapy.
Methods and participant characteristics in the Cancer Risk in Vegetarians Consortium: A cross-sectional analysis across 11 prospective studies
Authors: Dunneram Yashvee , Lee Jia Yi , Watling Cody Z. , Fraser Gary E , Miles Fayth , Prabhakaran Dorairaj , Shridhar Krithiga , Kondal Dimple , Mohan Viswanathan , Ali Mohammed K. , Venkat Narayan Kabayam M. , Tandon Nikhil , Tong Tammy Y. N. , Chiu Tina H.T. , Lin Ming-Nan , Lin Chin-Lon , Yang Hsin-Chou , Liang Yu-Jen , Greenwood Darren C. , Du Huaidong , Chen Zhengming , Yu Canqing , Kakkoura Maria G. , Reeves Gillian K. , Papier Keren , Floud Sarah , Sinha Rashmi , Liao Linda M. , Loftfield Erikka , Cade Janet E. , Key Timothy J. , Perez-Cornago Aurora 
Published: January 2024

AbstractBackgroundThe associations of vegetarian diets with risks for site-specific cancers have not been estimated reliably due to the low number of vegetarians in previous studies. Therefore, the Cancer Risk in Vegetarians Consortium was established.ObjectiveTo describe and compare the baseline characteristics between non-vegetarian and vegetarian diet groups and between the collaborating studies.MethodsWe harmonised individual-level data from 11 prospective cohort studies in the UK, US, India, China, and Taiwan. Comparisons of food intakes, sociodemographic and lifestyle factors were made between diet groups and between cohorts using descriptive statistics.Results2.3 million participants were included; 66% women and 34% men, with mean ages at recruitment of 57 (SD: 7.8) and 57 (8.6) years, respectively. There were 2.1 million meat eaters, 60,903 poultry eaters, 44,780 pescatarians, 81,165 vegetarians, and 14,167 vegans. Food intake differences between the diet groups varied across the cohorts; for example, fruit and vegetable intakes were generally higher in vegetarians than in meat eaters in all the cohorts except in China. BMI was generally lower in vegetarians, particularly vegans, except for the cohorts in India and China. In general, but with some exceptions, vegetarians were also more likely to be highly educated and physically active and less likely to smoke. In the available resurveys, stability of diet groups was high in all the cohorts except in China.ConclusionsFood intakes and lifestyle factors of both non-vegetarians and vegetarians varied markedly across the individual cohorts, which may be due to differences in both culture and socioeconomic status, as well as differences in questionnaire design. Therefore, care is needed in the interpretation of the impacts of vegetarian diets on cancer risk.
Dementia risk factors in former contact sports participants: prospective cohort study
Authors: Batty G. David , Bell Steven , Kujala Urho M. , Sarna Seppo J. , Kaprio Jaakko 
Published: January 2024

AbstractBackgroundThe elevated dementia incidence in retired contact sport participants might be explained by a higher prevalence of established risk factors for the disease relative to the general population.MethodsIn this cohort study, former elite participants active between 1920 and 1965 in soccer (N=303), boxing (N=281), and wrestling (N=318) were recruited using sports yearbooks and records of sports associations. Men in a population control group were identified using records from a compulsory medical examination (N=1712). All study members were linked to hospital registers (1970-2015) and self-completion questionnaires were circulated (1985, 1995) from which we captured data on nine established risk factors for dementia: hypertension and diabetes status, alcohol intake, loneliness, depressive symptoms, cigarette smoking, body weight, educational attainment, and physical activity.ResultsThere was little suggestion that former participants in contact sports had a higher prevalence of dementia risk factors relative to the general population. Rather, the balance of evidence was for more favourable risk factor levels in former athletes, as was particularly evident for ever having smoked cigarettes (range in odds ratios [95% confidence interval]: 0.32 [0.21, 0.48] for wrestling to 0.52 [0.36, 0.75] for soccer) and leisure-time physical activity (range in beta coefficients [95% confidence interval]: 1.34 [0.66, 2.02] for soccer to 1.80 [1.07, 2.52] for boxing).ConclusionsThe increased dementia rates in retired contact sport participants evident in epidemiological studies is unlikely to be explained by the risk factors examined here. This implicates other characteristics of contact sports, including a history of repeated head impact.
Beyond Hypertension: Examining Variable Blood Pressure’s Role in Cognition and Brain Structure
Authors: Morrison Cassandra , Oliver Michael D. , Kamal Farooq , Dadar Mahsa ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2024

Structured AbstractImportanceHypertension is a known risk factor for cognitive decline and structural brain changes in aging and dementia. In addition to high blood pressure (BP), individuals may also experience variable BP, meaning that their BP fluctuates between normal and high. It is currently unclear what the effects of variable BP are on cognition and brain structure.ObjectiveTo investigate the influence of BP on cognition and brain structure in older adults.Design, Setting, and ParticipantsThis longitudinal cohort study included data from the Rush Alzheimer’s Disease Center Research Resource Sharing Hub (RUSH) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Participants from the two studies were included if they had BP measurements and either cognitive scores or MRI scans from at least one visit.Main Outcomes and MeasuresLongitudinal gray matter, white matter, white matter hyperintensity volumes, postmortem neuropathology information, as well as cognitive test scores.ResultsA total of 4606 participants (3429 females, mean age = 76.8) with 32776 follow-ups (mean = 7 years) from RUSH and 2114 participants (1132 females, mean age = 73.3) with 9827 follow-ups (mean = 3 years) from ADNI were included in this study. Participants were divided into one of three groups: 1) normal BP, high BP, or variable BP. Older adults with variable BP exhibited the highest rate of cognitive decline followed by high BP and then normal BP. Increased GM volume loss and WMH burden was also observed in variable BP compared to high and normal BP. With respect to post-mortem neuropathology, both variable and high BP had increased severities compared to normal BP. Importantly, results were consistent across the RUSH and ADNI participants, supporting the generalizability of the findings.Conclusion and RelevanceLimited research has examined the long-term impact of variable BP on cognition and brain structure. These findings show the importance that both high and variable BP have on cognitive decline and structural brain changes. Structural damages caused by variable BP may reduce resilience to future dementia-related pathology and increased risk of dementia. Improved treatment and management of variable BP may help reduce cognitive decline in the older adult population.
Temporal and spatial dynamics within the fungal microbiome of grape fermentation
Authors: Onetto Cristobal A. , Ward Chris M. , Van Den Heuvel Steven , Hale Laura , Cuijvers Kathleen , Borneman Anthony R. 
Published: January 2024

AbstractWine fermentation is a highly complex and competitive environment, imposing harsh selective pressures on fungal community ecology and diversity. The composition of fungal communities inhabiting the surface of grapes will directly impact fermentation progression, wine quality, and contribute to the distinctiveness between wines from different geographical regions. Despite this, the extent of microbial community diversity between geographies, termed ‘microbial terroir,’ remains highly debated. We amassed a large survey of grape spontaneous ferments over six years, encompassing 3105 fungal microbiomes across 14 geographically separated grape-growing regions, and nine grape cultivars. Investigation into the biodiversity of these ferments identified that few high abundance genera form the core of the initial grape microbiome. In line with previous studies, various consistent taxa were linked to specific geographical locations and grape varieties. However, these taxa accounted for a small portion of the overall diversity in the dataset. Through unsupervised clustering, we identified three distinct community types in the grape fungal microbiome, each exhibiting variations in the abundance of key genera. Analysing ferments across temporal and spatial scales revealed significant differences in species richness and compositional heterogeneity between wineries and grape growing regions. However, microbial communities were transient between years in the same winery, regularly transitioning between the three broad community types. We then investigated microbial community composition throughout the fermentative process and observed that initial microbial community composition is predictive of the diversity during the early stages of fermentation, withHanseniaspora uvarumdetected as the main non-Saccharomycesspecies within this large cohort of samples. Our results help to formulate a clear understanding of the spatial and temporal characteristics of the grape juice fungal microbiome and suggest that these communities are mainly defined by the grape niche and in a minor way shaped by local environmental conditions.
Sox9links biliary maturation to branching morphogenesis
Authors: Hrncir Hannah R , Bombin Sergei , Goodloe Brianna , Hogan Connor B , Jadi Othmane , Gracz Adam D 
Published: January 2024

SUMMARYBranching morphogenesis couples cellular differentiation with development of tissue architecture. Intrahepatic bile duct (IHBD) morphogenesis is initiated with biliary epithelial cell (BEC) specification and eventually forms a heterogeneous network of large ducts and small ductules. Here, we show thatSox9is required for developmental establishment of small ductules. IHBDs emerge as a webbed structure by E15.5 and undergo morphological maturation through 2 weeks of age. Developmental knockout ofSox9leads to decreased postnatal branching morphogenesis, manifesting as loss of ductules in adult livers. In the absence ofSox9, BECs fail to mature and exhibit elevated TGF-β signaling and Activin A. Activin A induces developmental gene expression and morphological defects in BEC organoids and represses ductule formation in postnatal livers. Our data demonstrate that adult IHBD morphology and BEC maturation is regulated by theSox9-dependent formation of precursors to ductules during development, mediated in part by downregulation of Activin A.
Gaze and Arrows: does the Gaze Following Patch in the posterior temporal cortex differentiate social and symbolic spatial cues?
Authors: Görner Marius , Ramzanpour Hamidreza , Dicke Peter , Thier Peter 
Published: January 2024

AbstractTheGaze Following Patch(GFP) is located in the posterior temporal cortex and has been described as a cortical module dedicated to processing other people’s gaze direction in a domain-specific manner. Thus, it appears to be the neural correlate of Baron-Cohen’s Eye-Direction Detector (EDD) which is one of the core modules in hisMindreading System- a neurocognitive model for theTheory of Mindconcept. Inspired by Jerry Fodor’s ideas on the modularity of the mind, Baron-Cohen proposed that, among other things, the individual modules are domain-specific. In the case of the EDD this means that it exclusively processes eye-like stimuli to extract gaze direction and that other stimuli, that may carry directional information as well, are processed elsewhere. If the GFP is indeed EDD’s neural correlate it must meet this expectation. To test this, we compared the GFP’s BOLD activity during gaze-direction following with the activity during arrow-direction following. Contrary to the expectation based on the assumption of domain specificity we did not find a differentiation between gaze and arrow-direction following. In fact, we were not able to reproduce the GFP as presented in previous studies. A possible explanation is that in the present study – unlike previous work –, the gaze stimuli did not contain an obvious change of direction that represented a visual motion. Hence, the critical stimulus component responsible for the identification of the GFP in previous experiments might have been visual motion.
Inflamed Natural Killer cells with adhesion defects are associated with a poor prognosis in Multiple Myeloma
Authors: Blanquart Eve , Ekren Rüçhan , Rigaud Bineta , Joubert Marie-Véronique , Baylot Virginie , Daunes Hélène , Cuisinier Marine , Villard Marine , Carrié Nadège , Mazzotti Céline , Baylot Virginie , Lucca Liliana E. , Perrot Aurore , Corre Jill , Walzer Thierry , Avet-Loiseau Hervé , Axisa Pierre-Paul , Martinet Ludovic 
Published: January 2024

ABSTRACTThe promising results obtained with immunotherapeutic approaches for multiple myeloma (MM) call for a better stratification of patients based on immune components. The most pressing being cytotoxic lymphocytes such as Natural Killer (NK) cells that are mandatory for MM surveillance and therapy. In this study, we performed a single cell RNA sequencing analysis of NK cells from 10 MM patients and 10 age/sex matched healthy donors (HD) that revealed important transcriptomic changes in NK cell landscape affecting both the bone marrow and peripheral blood compartment. The frequency of mature cytotoxic “CD56dim” NK cell subsets was reduced in MM patients at the advantage of late-stage NK cell subsets expressing NFκB and IFN-I inflammatory signatures. These NK cell subsets accumulating in MM patients were characterized by a low CD16 and CD226 expression and poor cytotoxic functions. MM CD16/CD226loNK cells also had adhesion defects with reduced LFA-1 integrin activation and actin polymerization that may account for their limited effector functionsin vitro. Finally, analysis of BM infiltrating NK cells in a retrospective cohort of 177 MM patients from the IFM 2009 trial demonstrated that a high frequency of NK cells and their low CD16 and CD226 expression were associated with a shorter overall survival. Thus, CD16/CD226loNK cells with reduced effector functions accumulate along MM development and negatively impact patients’ clinical outcome. Given the growing interest in harnessing NK cells to treat myeloma, this improved knowledge around MM-associated NK cell dysfunction will stimulate the development of more efficient immunotherapeutic drugs against MM.Scientific category:Lymphoid Neoplasia; Immunobiology and Immunotherapy.KEY POINTSMM patients have increased CD16/CD226lowNK cell subsets characterized by “inflammatory” signatures and reduced effector functions.The frequency of CD16/CD226lowNK cells correlate with MM patient clinical outcome
DORA: an interactive map for the visualization and analysis of ancient human DNA and associated data
Authors: Harris Keith D. , Greenbaum Gili 
Published: January 2024

AbstractThe ability to sequence ancient genomes has revolutionized the way in which we study evolutionary history by providing access to the most important aspect of evolution — time. Until recently, studying human demography, ecology, biology, and history using population genomic inference relied on contemporary genomic datasets. Over the past decade, the availability of human ancient DNA (aDNA) has increased rapidly, almost doubling every year, opening the way for spatiotemporal studies of ancient human populations. However, the multidimensionality of aDNA, with genotypes having temporal, spatial and genomic coordinates, and the need to integrate multiple sources of data, poses a challenge for developing meta-analyses pipelines. To address this challenge, we developed a publicly-available interactive tool,DORA, which integrates multiple data types, genomic and non-genomic, in a unified interface. This web-based tool allows users to browse sample metadata along with additional layers of information, such as population structure, climatic data, and unpublished samples. Users can then perform analyses on genotypes of these samples, or export sample subsets for external analyses.DORAintegrates analyses and visualizations in a single intuitive interface, resolving the technical issues of combining datasets from different sources and formats, and allowing researchers to focus on analysis and the scientific questions that can be addressed through analysis of aDNA datasets.