bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simple statistical framework for small sample studies
Authors: Schwarzkopf D. Samuel , Huang Zien 
Published: September 2023

AbstractMost studies in psychology, neuroscience, and life science research make inferences about how strong an effect is on average in the population. Yet, many research questions could instead be answered by testing for the universality of the phenomenon under investigation. By using reliable experimental designs that maximise both sensitivity and specificity of individual experiments, each participant or subject can be treated as an independent replication. This approach is common in certain subfields. To date, there is however no formal approach for calculating the evidential value of such small sample studies and to definea priorievidence thresholds that must be met to draw meaningful conclusions. Here we present such a framework, based on the ratio of binomial probabilities between a model assuming the universality of the phenomenon versus the null hypothesis that any incidence of the effect is sporadic. We demonstrate the benefits of this approach, which permits strong conclusions from samples as small as 2-5 participants and the flexibility of sequential testing. This approach will enable researchers to preregister experimental designs based on small samples and thus enhance the utility and credibility of such studies.
Shifting from correlations to dynamics in the study of human prehistorical resilience to extreme climatic shifts
Authors: Ben-Oren Yotam , Jaffe Yitzchak , Kolodny Oren 
Published: September 2023

AbstractIn recent years there has been a growing body of research on human resilience to extreme climatic shifts in the past. Most studies focus on comparing archaeological records prior to a perceived climatic shift with those after it, to investigate a causal relationship between the two. Although these comparisons are important, they are limited in their potential to facilitate causal understanding of the factors that determined the human response to climate change. We assert that for such understanding, it is necessary to explicitly consider prior processes that could have made certain populations more resilient to the extreme climatic shift. This assertion calls for a new focus on the cultural and demographicdynamicsin prehistorical populations, over the generations thatprecededthe climatic shift. In this article, we lay out several mechanisms of cultural evolution that – together with the experienced climatic dynamics prior to extreme climatic shifts – may have determined populations’ abilities to cope with them. This endeavor allows us to outline alternative hypotheses regarding what determined the fate of different human groups. These, in turn, may help direct the collection and analysis of archaeological data and to highlight modalities within it that may be helpful for inference of the mechanisms that determined populations’ resilience to climatic shifts.
InSituCor: a toolkit for discovering non-trivial spatial correlations in spatial transcriptomics
Authors: Danaher Patrick , McGuire Dan , Patrick Michael , Kroeppler David , Zhai Haiyan , Schmid Joachim , Beechem Joseph M. 
Published: September 2023

AbstractSpatial transcriptomics presents the best kind of problem: how to find the many biological insights hidden within complex datasets. Spatially correlated genes can reveal high-interest phenomena like cell-cell interactions and latent variables. We introduce InSituCor, a toolkit for discovering modules of spatially correlated genes. A major contribution is that InSituCor returns only correlations not explainable by obvious factors like the cell type landscape; this spares precious analyst effort for non-trivial findings. InSituCor supports both unbiased discovery of whole-dataset correlations and knowledge-driven exploration of genes of interest. As a special case, it evaluates ligand-receptor pairs for spatial co-regulation.
Cardiac glycosides protect wormseed wallflower (Erysimum cheiranthoides) against some, but not all, glucosinolate-adapted herbivores
Authors: Younkin Gordon C. , Alani Martin L. , Capador Anamaría Páez , Fischer Hillary D. , Mirzaei Mahdieh , Hastings Amy P. , Agrawal Anurag A. , Jander Georg 
Published: September 2023

SUMMARYThe chemical arms race between plants and insects is foundational to the generation and maintenance of biological diversity. We asked how the evolution of a novel defensive compound in an already well-defended plant lineage impacts interactions with diverse herbivores.Erysimum cheiranthoides(Brassicaceae), which produces both ancestral glucosinolates and novel cardiac glycosides, served as a model.We analyzed gene expression to identify cardiac glycoside biosynthetic enzymes inE. cheiranthoidesand characterized these enzymes via heterologous expression and CRISPR/Cas9 knockout. UsingE. cheiranthoidescardiac glycoside-deficient lines, we conducted insect experiments in both the laboratory and field.EcCYP87A126 initiates cardiac glycoside biosynthesis via sterol side chain cleavage, andEcCYP716A418 has a role in cardiac glycoside hydroxylation. InEcCYP87A126 knockout lines, cardiac glycoside production was eliminated. Laboratory experiments with these lines revealed that cardiac glycosides were highly effective defenses against two species of glucosinolate-tolerant specialist herbivores but did not protect against all crucifer-feeding specialist herbivores in the field. Cardiac glycosides had lesser to no effect on two broad generalist herbivores.These results begin elucidation of theE. cheiranthoidescardiac glycoside biosynthetic pathway and demonstratein vivothat cardiac glycoside production allowsErysimumto escape from some, but not all, specialist herbivores.
Personality heterophily and friendship as drivers for successful cooperation
Authors: Bhattacharjee Debottam , Waasdorp Sophie , Middelburg Esmee , Sterck Elisabeth H.M. , Massen Jorg J.M. 
Published: September 2023

AbstractCooperation is widespread and arguably a pivotal evolutionary force in maintaining animal societies. Yet, proximately, what underlying motivators drive individuals to cooperate remains relatively unclear. Since ‘free-riders’ can exploit the benefits by cheating, selecting the right partner is paramount. Such decision rules need not be based on complex calculations and can be driven by cognitively less-demanding mechanisms, like social relationships (e.g., kinship, non-kin friendships, dyadic tolerance), social status (e.g., dominance hierarchies) and personalities (social and non-social traits); however, holistic evidence related to those mechanisms is scarce. Using the classical ‘loose-string paradigm’, we tested cooperative tendencies of a hierarchical primate, the long-tailed macaque (Macaca fascicularis). We studied three groups (n=32) in social settings, allowing free partner choice. We supplemented cooperation with observational and experimental data on social relationships, dominance hierarchies, and personality. Friendship and dissimilarity in a non-social ‘exploration’ personality trait predicted the likelihood of cooperative dyad formation. Furthermore, the magnitude of cooperative success was positively associated with friendship, low rank-distance, and dissimilarity in an ‘activity-sociability’ personality trait. Kinship did not affect cooperation. While some findings align with prior studies, the evidence of (non-social)personality heterophily promoting cooperation may deepen our understanding of the proximate mechanisms and, broadly, the evolution of cooperation.
Destabilization of mRNAs enhances competence to initiate meiosis in mouse spermatogenic cells
Authors: Pfaltzgraff Natalie G. , Liu Bingrun , de Rooij Dirk G. , Page David C. , Mikedis Maria M. 
Published: September 2023

ABSTRACTThe specialized cell cycle of meiosis transforms diploid germ cells into haploid gametes. In mammals, diploid spermatogenic cells acquire the competence to initiate meiosis in response to retinoic acid. Previous mouse studies revealed that MEIOC interacts with RNA-binding proteins YTHDC2 and RBM46 to repress mitotic genes and promote robust meiotic gene expression in spermatogenic cells that have initiated meiosis. Here, we used the enhanced resolution of scRNA-seq, and bulk RNA-seq of developmentally synchronized spermatogenesis, to define how MEIOC molecularly supports early meiosis in spermatogenic cells. We demonstrate that MEIOC mediates transcriptomic changes before meiotic initiation, earlier than previously appreciated. MEIOC, acting with YTHDC2 and RBM46, destabilizes its mRNA targets, including transcriptional repressorsE2f6andMga, in mitotic spermatogonia. MEIOC thereby derepresses E2F6- and MGA-repressed genes, includingMeiosinand other meiosis-associated genes. This confers on spermatogenic cells the molecular competence to, in response to retinoic acid, fully activate transcriptional regulator STRA8-MEIOSIN, required for the meiotic G1/S phase transition and meiotic gene expression. We conclude that in mice, mRNA decay mediated by MEIOC-YTHDC2-RBM46 enhances the competence of spermatogenic cells to initiate meiosis.SUMMARY STATEMENTRNA-binding complex MEIOC-YTHDC2-RBM46 destabilizes its mRNA targets, including transcriptional repressors. This activity facilitates the retinoic acid-dependent activation ofMeiosingene expression and transition into meiosis.
Assessing molecular phylogenetics of Hydroptilidae (Trichoptera) subfamily lineages, with notes on biogeography
Authors: Murray-Stoker Kelly M. , McCauley Shannon J. 
Published: September 2023

AbstractThe microcaddisfly family Hydroptilidae is the most species-rich within the insect order Trichoptera and has a global distribution. The taxonomy and systematics of this group remains understudied in proportion to its diversity. Here, we present a phylogenetic assessment of subfamily relationships that includes five of the six Hydroptilidae subfamilies (Hydroptilinae, Leucotrichiinae, Ochrotrichiinae, Orthotrichiinae, and Stactobiinae) using publicly available molecular data. Our analyses recovered Leucotrichiinae, Ochrotrichiinae, and Stactobiinae as monophyletic and Hydroptilinae as paraphyletic. Based on the diversity and distribution of taxa, much more representation of species is needed to fully understand the relationships of subfamilies; however, our results suggest a need to revisit the placement ofIthytrichia, which concurs with other recent molecular work on Hydroptilidae. Further clarity into the relationships of Hydroptilidae will be important for understanding the variability and phylogenetic signal of ecological traits.
Looming detection in complex dynamic visual scenes by interneuronal coordination of motion and feature pathways
Authors: Gu Bo , Feng Jianfeng , Song Zhuoyi 
Published: September 2023

ABSTRACTDetecting looming signals for collision avoidance faces challenges in real-world scenarios due to interference from moving backgrounds. Astonishingly, animals, like insects with limited neural systems, adeptly respond to looming stimuli while moving at high speeds. Existing insect-inspired looming detection models integrate either motion-pathway or feature-pathway signals, remaining susceptible to dynamic visual scene interference. We propose that coordinating interneuron signals from the two pathways could elevate looming detection performance in dynamic conditions. We used artificial neural network (ANN) to build a combined-pathway model based onDrosophilaanatomy. The model exhibits convergent neural dynamics with biological counterparts after training. In particular, a multiplicative interneuron operation enhances looming signal patterns. It reduces background interferences, boosting looming detection accuracy and enabling earlier warnings across various scenarios, such as 2D animated scenes, AirSim 3D environments, and real-world situations. Our work presents testable biological hypotheses and a promising bio-inspired solution for looming detection in dynamic visual environments.
Tumor sialylation controls effective anti-cancer immunity in breast cancer
Authors: Mereiter Stefan , Jonsson Gustav , Oliveira Tiago , Helm Johannes , Hoffmann David , Abeln Markus , Jochum Ann-Kristin , Jochum Wolfram , Kellner Max J. , Feith Marek , Tkalec Vanessa , Wasilewska Karolina , Jiao Jie , Emsenhuber Lukas , Holstein Felix , Obenauf Anna C. , Lordello Leonardo , Scoazec Jean-Yves , Kroemer Guido , Zitvogel Laurence , Ali Omar Hasan , Flatz Lukas , Gerardy-Schahn Rita , Münster-Kühnel Anja , Stadlmann Johannes , Penninger Josef M. 
Published: September 2023

AbstractBreast cancer is the most common cancer among women. However, the use of immune checkpoint inhibitors, that have revolutionized treatment of multiple cancers, unfortunately remain largely ineffective in most breast cancer patients. Here, we report the most comprehensive glycoproteome map in breast tumor cells, pointing to a key role of sialic acid modifications in mammary cancer. Genetic and pharmacologic inhibition of sialylation repolarizes the tumor microenvironment, leading to a reduction in myeloid-derived suppressor cells and a significant increase in Tcf7+memory and CD8+effector T cells. Mechanistically, sialylation controls cell surface expression of MHC class I and PD-1-ligand on the tumor cells. Functionally, in vivo interference with sialylation on breast cancer cells licenses CD8+T cells to effectively kill the tumors. In multiple immunotherapy-resistant breast tumor models, we also show that the abrogation of sialylation sensitizes to anti-PD-1 immune checkpoint therapy. We further demonstrate that hyper-sialylation occurs in over half of human breast cancers tested and correlates with poor T cell infiltration. Our results establish sialylation as a central immunoregulator in breast cancer, orchestrating multiple pathways of immune evasion. Targeting tumor sialylation licenses immunologically inert mammary tumors to be efficiently eliminated by anti-cancer immunity and sensitizes to immune checkpoint therapy.
Unmasking AlphaFold: integration of experiments and predictions in multimeric complexes
Authors: Mirabello Claudio , Wallner Björn , Nystedt Björn , Azinas Stavros , Carroni Marta 
Published: September 2023

Since the release of AlphaFold, researchers have actively refined its predictions and attempted to integrate it into existing pipelines for determining protein structures. These efforts have introduced a number of functionalities and results at the latest Critical Assessment of protein Structure Prediction edition (CASP15), resulting in a marked improvement in the prediction of multimeric protein structures. However, AlphaFold’s capability of predicting large protein complexes is still limited and integrating experimental data in the prediction pipeline is not straightforward. In this study, we introduce AF_unmasked to overcome these limitations. Our results demonstrate that AF_unmasked can integrate experimental information to build larger or hard to predict protein assemblies with high confidence. The resulting predictions can help interpret and augment experimental data. This new approach generates near-perfect structures even when little to no evolutionary information is available and imperfect experimental structures are used as a starting point. AF_unmasked fills incomplete structures by a procedure called“structural inpainting”, which may provide insights into protein dynamics. In summary, AF_unmasked provides an easy-to-use method that efficiently integrates experiments to predict large protein complexes more confidently.Codegithub.com/clami66/AF_unmasked
Tonic and phasic transcutaneous auricular vagus nerve stimulation both evoke rapid and transient pupil dilation
Authors: Skora Lina , Marzecová Anna , Jocham Gerhard 
Published: September 2023

AbstractBackgroundTranscutaneous auricular vagus nerve stimulation (tVNS or taVNS) is a non-invasive method of electrical stimulation of the afferent pathway of the vagus nerve, suggested to drive changes in putative physiological markers of noradrenergic activity, including pupil dilation.ObjectiveHowever, it is unknown whether different taVNS modes can map onto the phasic and tonic modes of noradrenergic activity. The effects of taVNS on pupil dilation in humans are inconsistent, largely due to differences in stimulation protocols. Here, we attempted to address these issues.MethodsWe investigated pupil dilation under phasic (1 s) and tonic (30 s) taVNS, in a pre-registered, single-blind, sham-controlled, within-subject cross-over design, in the absence of a behavioural task.ResultsPhasic taVNS induced a rapid increase in pupil size over baseline, significantly greater than under sham stimulation, which rapidly declined after stimulation offset. Tonic taVNS induced a similarly rapid (and larger than sham) increase in pupil size over baseline, returning to baseline within 5 s, despite the ongoing stimulation. Thus, both active and sham tonic modes closely resembled the phasic effect. There were no differences in tonic baseline pupil size, and no sustained effects of stimulation on tonic baseline pupil size.ConclusionsThese results suggest that both phasic- and tonic-like taVNS under the standard stimulation parameters may modulate primarily the phasic mode of noradrenergic activity, as indexed by evoked pupil dilation, over and above somatosensory effects. This result sheds light on the temporal profile of phasic and tonic stimulation, with implications for their applicability in further research.
Non-invasive assessment of stimulation-specific changes in cerebral glucose metabolism with functional PET
Authors: Godbersen Godber M , Falb Pia , Klug Sebastian , Silberbauer Leo R , Reed Murray B , Nics Lukas , Hacker Marcus , Lanzenberger Rupert , Hahn Andreas 
Published: September 2023

ABSTRACTFunctional positron emission tomography (fPET) with [18F]FDG allows one to quantify stimulation-induced dynamics in glucose metabolism independent of neurovascular coupling. However, the gold standard for quantification requires arterial blood sampling, which can cause discomfort for the participant and increases complexity of the experimental protocol. These constraints have limited the widespread applicability of fPET, especially in the clinical routine. Therefore, we introduce a novel approach, which enables the assessment of the dynamics in cerebral glucose metabolism without the need for an input function.MethodsWe tested the validity of a mathematical derivation on the basis of two independent data sets (DS). For DS1, 52 healthy volunteers (23.2 ± 3.3 years, 24 females) completed a visuo-spatial motor coordination task (the video game Tetris®) and for DS2, 18 healthy participants (24.2 ± 4.3 years, 8 females) performed an eyes-open/finger tapping task, both during a [18F]FDG fPET scan. Task-specific changes in metabolism were assessed with the general linear model (GLM) and cerebral metabolic rate of glucose (CMRGlu) was quantified with the Patlak plot as the reference standard. Simplified outcome parameters, such as GLM beta values of task effects and percent signal change (%SC) of both parameters were estimated. These were compared for task-relevant brain regions and on a whole-brain level.ResultsIn general, we observed higher agreement with the reference standard for DS1 (radiotracer administration as bolus + constant infusion) compared to DS2 (constant infusion only). Across both data sets, strong correlations were found between regional task-specific beta estimates and CMRGlu (r = 0.763…0.912). Additionally, %SC of beta values exhibited excellent agreement with %SC of CMRGlu (r = 0.909…0.999). Average activation maps showed a high spatial similarity between CMRGlu and beta estimates (Dice = 0.870…0.979) as well as %SC (Dice = 0.932…0.997), respectively.ConclusionTask-specific changes in glucose metabolism can be reliably estimated using %SC of GLM beta values, eliminating the need for any blood sampling. This approach streamlines fPET imaging, albeit with the trade-off of being unable to quantify baseline metabolism. The proposed simplification enhances the applicability of fPET, allowing for widespread employment in research settings and clinical investigations.GRAPHICAL ABSTRACT
Focal acetylcholinergic modulation of the human midcingulo-insular network during attention: Meta-analytic neuroimaging and behavioral evidence
Authors: Chakraborty Sudesna , Lee Sun Kyun , Arnold Sarah M. , Haast Roy A.M. , Khan Ali R. , Schmitz Taylor W. 
Published: September 2023

AbstractThe basal forebrain cholinergic neurons provide acetylcholine to the cortex via large projections. Recent molecular imaging work in humans indicates that the cortical cholinergic innervation is not uniformly distributed, but rather may disproportionately innervate cortical areas relevant to supervisory attention. In this study, we therefore reexamined the spatial relationship between acetylcholinergic modulation and attention in the human cortex using meta-analytic strategies targeting both pharmacological and nonpharmacological neuroimaging studies. We found that pharmaco-modulation of acetylcholine evoked both increased activity in the anterior cingulate and decreased activity in the opercular and insular cortex. In large independent meta-analyses of non-pharmacological neuroimaging research, we demonstrate that during attentional engagement these cortical areas exhibit (1) task-related co-activation with the basal forebrain, (2) task-related co-activation with one another, and (3) spatial overlap with dense cholinergic innervations originating from the BF, as estimated by multimodal PET and MR imaging. Finally, we provide meta-analytic evidence that pharmaco-modulation of acetylcholine also induces a speeding of responses to targets with no apparent tradeoff in accuracy. In sum, we demonstrate in humans that acetylcholinergic modulation of midcingulo-insular hubs of the ventral attention/salience network via basal forebrain afferents may coordinate selection of task relevant information, thereby facilitating cognition and behavior.
BK channel gain-of-function disrupts limb control by suppressing neurotransmission during a critical developmental window
Authors: Lowe Simon A. , Wilson Abigail D. , Aughey Gabriel , Banarjee Animesh , Goble Talya , Simon-Batsford Nell , Sanderson Angelina , Kratschmer Patrick , Balogun Maryam , Gao Hao , Aw Sherry S. , Jepson James E.C. 
Published: September 2023

SUMMARYGain-of-function mutations in BK potassium channels (BK GOF) cause debilitating involuntary limb movements. BK channels modulate action potential shape and neurotransmission in mature neurons, yet some BK GOF mutations also cause neurodevelopmental morbidities. Thus, whether BK GOF impairs limb control by altering the excitation/inhibition of mature motor circuits, or by disrupting their development, remains unclear. To address this issue, we developed a genetic method enabling spatiotemporal control of BK channel expression in neurons of the fruit fly,Drosophila. In concert with high-resolution measurements of limb kinematics, we demonstrate that GOF BK channels act during a narrow neurodevelopmental period to perturb limb control in adult flies. During this period, BK GOF alters synaptic localisation of the key active zone protein Bruchpilot and suppresses excitatory neurotransmission. In a wild-type background, we find that reducing neural activity during neurodevelopment yields similar motor defects to those observed in BK GOF flies. Conversely, enhancing neural excitability during development rescues alterations in limb kinematics in BK GOF flies. Collectively, our results suggest that BK GOF perturbs limb control largely by disrupting activity-dependent aspects of neuronal development.