bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender dysphoria and sexual euphoria – A Bayesian perspective on the influence of gender-affirming hormone therapy on sexual arousal
Authors: Klöbl Manfred , Reed Murray Bruce , Handschuh Patricia , Kaufmann Ulrike , Konadu Melisande Elisabeth , Ritter Vera , Spurny-Dworak Benjamin , Kranz Georg S. , Lanzenberger Rupert , Spies Marie 
Published: November 2021

AbstractWhile the concept of sexual orientation is more clearly defined in cisgender, this is less so in transgender individuals. Both experienced gender and sex hormones have a relation to sexual preferences, arousal in response to erotic stimuli, and thus sexual orientation. In transgender individuals sexual orientation occasionally changes before or during transition, which may involve gender-affirming hormone therapy. Using functional magnetic resonance imaging, we investigated whether the neuronal and behavioral patterns of sexual arousal in transgender individuals moved from the given (before) to their chosen gender after 4.5 months of hormone therapy. To this aim, trans women and men as well as age-matched cisgender controls rated visual stimuli showing heterosexual, lesbian or gay intercourse for subjective sexual arousal. Utilizing a Bayesian framework allowed us to incorporate behavioral findings in cisgender individuals of different sexual orientations. The hypothesized changes in response patterns could indeed be observed in the behavioral responses to the single but not the differentiation between stimulus categories with the strongest results for trans men and lesbian scenes. Activation of the ventral striatum supported our hypothesis only for lesbian scenes in trans women. This prominent role of lesbian stimuli might be explained by their differential responses in cis women and men. We show that correlates of sexual arousal in transgender individuals might change in direction of the chosen gender. Future investigations longer into transition might resolve the discrepancy on behavioral and neuronal levels.
Long-term decreased cannabinoid type-1 receptor activity restores specific neurological phenotypes in the Ts65Dn mouse model of Down syndrome
Authors: Vázquez-Oliver Anna , Pérez-García Silvia , Pizarro Nieves , Molina-Porcel Laura , de la Torre Rafael , Maldonado Rafael , Ozaita Andrés 
Published: November 2021

AbstractIntellectual disability is the most prevalent and limiting hallmark of Down syndrome (DS), without any pharmacological treatment available. Neurodegeneration and neuroinflammation are relevant neurological features of DS reaching to early development of Alzheimer’s disease. Preclinical evidence suggests that the endocannabinoid system, an important neuromodulator on cognition and neuroinflammation, could act as beneficial target in DS. Indeed, cannabinoid type-1 receptor (CB1R) activity was enhanced in the hippocampus of young-adult trisomic Ts65Dn mice, a well-characterized surrogate model of DS. In previous studies, inhibition of CB1R, was able to restore key neurological deficits in this mouse model. To determine the possible clinical relevance of this target, it is mandatory to evaluate the long-term consequences of attenuated CB1R activity and to minimize the possible side-effects associated to this mechanism. We found that CB1R expression was significantly enhanced in the hippocampus brains of aged DS subjects. Similarly, middle-aged trisomic mice showed enhanced CB1R expression. Long-term oral administration of a low dose of the CB1R specific antagonist rimonabant was administered to male and female Ts65Dn trisomic and wild-type mice from the time of weaning to 10 months, an age when signs of neurodegeneration have been described in the model. CB1R inhibition resulted in significant cognitive improvement in novel object-recognition memory in trisomic male and female mice, reaching a similar performance to that of wild-type littermates. Interestingly, this long-term rimonabant treatment modify locomotor activity, anxiety-like behavior, body weight or survival rates. Brain analysis at 10 months of age revealed noradrenergic and cholinergic neurodegeneration signs in trisomic mice that were not modified by the treatment, although the alterations in hippocampal microglia morphology shown by vehicle-treated trisomic mice was normalized in trisomic mice exposed to rimonabant. Altogether, our results demonstrate a sustained pro-cognitive effect of CB1R inhibition at doses that do not produce major side effects that could be associated to an anti-inflammatory action, suggesting a potential interest in this target of to preserve cognitive functionality in DS.
The role of indirect effects in coevolution as mutualism transitions into antagonism
Authors: Pedraza Fernando , Liu Hanlun , Gawecka Klementyna A. , Bascompte Jordi 
Published: November 2021

AbstractSpecies interactions have evolved from antagonistic to mutualistic and back several times throughout life’s history. Yet, it is unclear how changes in the type of interaction between species alter the coevolutionary dynamics of entire communities. This is a pressing matter, as transitions from mutualisms to antagonisms may be becoming more common with human-induced global change. Here, we combine network and evolutionary theory to simulate how shifts in interaction types alter the coevolution of empirical communities. We show that as mutualistic networks shift to antagonistic, selection imposed by direct partners begins to outweigh that imposed by indirect partners. This weakening of indirect effects is associated with communities losing their tight integration of traits and increasing their rate of adaptation. The above changes are more pronounced when specialist consumers are the first species to switch to antagonism. A shift in the outcome of species’ interactions may therefore reverberate across communities and alter the direction and speed of coevolution.
Causal contributions of neural noise to left frontal networks subtending the modulation of conscious visual perception in the human brain
Authors: Stengel Chloé , Amengual Julià L. , Moreau Tristan , Valero-Cabré Antoni 
Published: November 2021

AbstractFor several decades, the field of human neurophysiology has focused on the role played by cortical oscillations in enabling brain function underpinning behaviors. In parallel, a less visible but robust body of work on the stochastic resonance phenomenon has also theorized contributions of neural noise − hence more heterogeneous, complex and less predictable activity − in brain coding. The latter notion has received indirect causal support via improvements of visual function during non-regular or random brain stimulation patterns. Nonetheless, direct evidence demonstrating an impact of brain stimulation on direct measures of neural noise is still lacking. Here we evaluated the impact of three non frequency-specific TMS bursts, compared to a control pure high-beta TMS rhythm, delivered to the left FEF during a visual detection task, on the heterogeneity, predictability and complexity of ongoing brain activity recorded with scalp EEG. Our data showed surprisingly that the three non frequency-specific TMS patterns did not prevent a build-up of local high-beta activity. Nonetheless, they increased power across broader or in multiple frequency bands compared to control purely rhythmic high-beta bursts tested along. Importantly, non frequency-specific patterns enhanced signal entropy over multiple time-scales, suggesting higher complexity and an overall induction of higher levels of cortical noise than rhythmic TMS bursts. Our outcomes provide indirect evidence on a potential modulatory role played by sources of stochastic noise on brain oscillations and synchronization. Additionally, they pave the way towards the development of novel neurostimulation approaches to manipulate cortical sources of noise and further investigate their causal role in neural coding.
Characterizing the short-latency evoked response to intracortical microstimulation across a multi-electrode array
Authors: Sombeck Joseph , Heye Juliet , Kumaravelu Karthik , Goetz Stefan M. , Peterchev Angel V. , Grill Warren M. , Bensmaia Sliman , Miller Lee E. 
Published: November 2021

AbstractObjectivePersons with tetraplegia can use brain-machine interfaces to make visually guided reaches with robotic arms. Without somatosensory feedback, these movements will likely be slow and imprecise, like those of persons who retain movement but have lost proprioception. Intracortical microstimulation (ICMS) has promise for providing artificial somatosensory feedback. If ICMS can mimic naturally occurring neural activity, afferent interfaces may be more informative and easier to learn than interfaces that evoke unnaturalistic activity. To develop such biomimetic stimulation patterns, it is important to characterize the responses of neurons to ICMS.ApproachUsing a Utah multi-electrode array, we recorded activity evoked by single pulses, and short (~0.2 s) and long (~4 s) trains of ICMS at a wide range of amplitudes and frequencies. As the electrical artifact caused by ICMS typically prevents recording for many milliseconds, we deployed a custom rapid-recovery amplifier with nonlinear gain to limit signal saturation on the stimulated electrode. Across all electrodes after stimulation, we removed the remaining slow return to baseline with acausal high-pass filtering of time-reversed recordings. With these techniques, we could record ~0.7 ms after stimulation offset even on the stimulated electrode.Main resultsWe recorded likely transsynaptically-evoked activity as early as ~0.7 ms after single pulses of stimulation that was immediately followed by suppressed neural activity lasting 10–150 ms. Instead of this long-lasting inhibition, neurons increased their firing rates for ~100 ms after trains. During long trains, the evoked response on the stimulated electrode decayed rapidly while the response was maintained on non-stimulated channels.SignificanceThe detailed description of the spatial and temporal response to ICMS can be used to better interpret results from experiments that probe circuit connectivity or function of cortical areas. These results can also contribute to the design of stimulation patterns to improve afferent interfaces for artificial sensory feedback.
A Field-Deployable Diagnostic Assay for the Visual Detection of Misfolded Prions
Authors: Christenson Peter R. , Li Manci , Rowden Gage , Schwabenlander Marc , Wolf Tiffany M. , Oh Sang-Hyun , Larsen Peter A. 
Published: November 2021

AbstractChronic Wasting Disease (CWD), a prion disease of cervids, has been identified across North America, Northern Europe and Korea. Diagnostic tools for the rapid and reliable detection of prion diseases are limited. Here, we combine gold nanoparticles (AuNPs) and quaking induced conversion (QuIC) technologies for the visual detection of amplified misfolded prion proteins from tissues of wild white-tailed deer infected with Chronic Wasting Disease (CWD). Our newly developed diagnostic test, MN-QuIC, enables both naked-eye and light-absorbance measurements for the detection of misfolded prions. The MN-QuIC assay leverages basic laboratory equipment that is cost-effective and portable, thus facilitating real-time prion diagnostics across a variety of settings. To test the portability of our assay, we deployed to a rural field station in southeastern Minnesota and tested for CWD on site. We successfully demonstrated that MN-QuIC is functional in a non-traditional laboratory setting by performing a blinded analysis in the field and correctly identifying all CWD positive and CWD not detected (independently confirmed with ELISA and/or IHC tests) animals at the field site, thus documenting the portability of the assay. Additionally, we show that electrostatic forces and concentration effects help govern the AuNP/prion interactions and contribute to the differentiation of CWD-prion positive and negative samples. We examined 17 CWD-positive and 24 CWD-not-detected white-tailed deer tissues that were independently tested using ELISA, IHC, and RT-QuIC technologies, and results secured with MN-QuIC were 100% consistent with these tests. We conclude that hybrid AuNP and QuIC assays, such as MN-QuIC, have great potential for sensitive, field-deployable diagnostics for a variety of protein misfolding diseases.
Effects of the expression of random sequence clones on growth and transcriptome regulation in Escherichia coli
Authors: Bhave Devika , Tautz Diethard 
Published: November 2021

AbstractComparative genomic analyses have provided evidence that new genetic functions can emerge out of random nucleotide sequences. Here, we apply a direct experimental approach to study the effects of plasmids harbouring random sequence inserts under the control of an inducible promoter. Based on data from previously described experiments dealing with the growth of clones within whole libraries, we extracted specific clones that had shown either negative or positive effects on relative cell growth. We analysed these individually with respect to growth characteristics and impact on the transcriptome. We find that candidate clones for negative peptides lead to growth arrest by eliciting a general stress response. Overexpression of positive clones, on the other hand, does not change the exponential growth rates of hosts, but they show a growth advantage over a neutral candidate clone when tested in direct competition experiments. Transcriptomic changes in positive clones are relatively moderate and specific to each clone. We conclude from our experiments that random sequence peptides are indeed a suitable source for the de novo evolution of genetic functions.
Transcriptional and mutational signatures of the aging germline
Authors: Witt Evan , Langer Christopher B , Svetec Nicolas , Zhao Li 
Published: November 2021

AbstractAging is a complex biological process that is accompanied by changes in gene expression and mutational load. In many species, including humans, older fathers pass on more paternally-derived de novo mutations; however, the cellular basis and cell types driving this pattern are still unclear. To explore the root causes of this phenomenon, we performed single-cell RNA-sequencing (scRNA-seq) on testes from young and old male Drosophila, as well as genomic sequencing (DNA-seq) on somatic tissues from the same flies. We found that early germ cells from old and young flies enter spermatogenesis with similar mutational loads, but older flies are less able to remove mutations during spermatogenesis. Mutations in old cells may also increase during spermatogenesis. Our data reveal that old and young flies have distinct mutational biases. Many classes of genes show increased post-meiotic expression in the germlines of older flies. Late spermatogenesis-enriched genes have higher dN/dS than early spermatogenesis-enriched genes, supporting the hypothesis that late spermatogenesis is a source of evolutionary innovation. Surprisingly, young fly enriched genes show higher dN/dS than old fly enriched genes. Our results provide novel insights into the role of the germline in de novo mutation.
Identification of biological processes and signaling pathways for the knockout of REV-ERB in mouse brain
Authors: Li Jing , Wang Wei , Gu Hanming 
Published: November 2021

AbstractREV-ERB is an orphan nuclear receptor that is widely expressed in the brain and inhibits transcriptional activities. A variety of genes affect the activity and expression of REV-ERB. In this study, our objective is to identify significant signaling pathways and biological processes in the knockout of the REV-ERB mouse brain. The GSE152919 dataset was originally created by using the Illumina HiSeq 4000 (Mus musculus). The KEGG and GO analyses suggested that biological processes “PPAR signaling”, “Hippo signaling”, and “Hypertrophic cardiomyopathy (HCM)” are mostly affected in the knockout of REV-ERB. Furthermore, we identified a number of genes according to the PPI network including NPAS2, CRY2, BMAL1, and CRY1 which were involved in the lack of REV-ERB in the brain. Therefore, our study provides further insights into the study of circadian clocks.
Somatic regulation of female germ cell regeneration and development in planarians
Authors: Khan Umair W. , Newmark Phillip A. 
Published: November 2021

SummaryFemale germ cells develop into oocytes, with the capacity for totipotency. In most animals, these remarkable cells are specified during development and cannot be regenerated. By contrast, planarians, known for their regenerative prowess, can regenerate germ cells. To uncover mechanisms required for female germ cell development and regeneration, we generated gonad-specific transcriptomes and identified genes whose expression defines progressive stages of female germ cell development. Strikingly, early female germ cells share molecular signatures with the pluripotent stem cells driving planarian regeneration. We uncovered spatial heterogeneity within somatic ovarian cells and found that a regionally enriched FoxL homolog is required for oocyte differentiation, but not specification, suggestive of functionally distinct somatic compartments. Unexpectedly, a neurotransmitter-biosynthetic enzyme, AADC, is also expressed in somatic gonadal cells, and plays opposing roles in female and male germ cell development. Thus, somatic gonadal cells deploy conserved factors to regulate germ cell development and regeneration in planarians.
Fine-tuning of deep language models as a computational framework of modeling listeners’ perspective during language comprehension
Authors: Tikochinski Refael , Goldstein Ariel , Yeshurun Yaara , Hasson Uri , Reichart Roi 
Published: November 2021

AbstractComputational Deep Language Models (DLMs) have been shown to be effective in predicting neural responses during natural language processing. This study introduces a novel computational framework, based on the concept of fine-tuning (Hinton, 2007), for modeling differences in interpretation of narratives based on the listeners’ perspective (i.e. their prior knowledge, thoughts, and beliefs). We draw on an fMRI experiment conducted by Yeshurun et al. (2017), in which two groups of listeners were listening to the same narrative but with two different perspectives (cheating versus paranoia). We collected a dedicated dataset of ~3000 stories, and used it to create two modified (fine-tuned) versions of a pre-trained DLM, each representing the perspective of a different group of listeners. Information extracted from each of the two fine-tuned models was better fitted with neural responses of the corresponding group of listeners. Furthermore, we show that the degree of difference between the listeners’ interpretation of the story - as measured both neurally and behaviorally - can be approximated using the distances between the representations of the story extracted from these two fine-tuned models. These models-brain associations were expressed in many language-related brain areas, as well as in several higher-order areas related to the default-mode and the mentalizing networks, therefore implying that computational fine-tuning reliably captures relevant aspects of human language comprehension across different levels of cognitive processing.
In Diverse Conditions Intrinsic Chromatin Condensates Have Liquid-like Material Properties
Authors: Gibson Bryan A. , Blaukopf Claudia , Lou Tracy , Doolittle Lynda K. , Finkelstein Ilya , Narlikar Geeta J. , Gerlich Daniel W. , Rosen Michael K. 
Published: November 2021

SUMMARYEukaryotic nuclear DNA is wrapped around histone proteins to form nucleosomes, which further assemble to package and regulate the genome. Understanding of the physical mechanisms that contribute to higher order chromatin organization is limited. Previously, we reported the intrinsic capacity of chromatin to undergo phase separation and form dynamic liquid-like condensates, which can be regulated by cellular factors. Recent work from Hansen, Hendzel, and colleagues suggested these intrinsic chromatin condensates are solid in all but a specific set of conditions. Here we show that intrinsic chromatin condensates are fluid in diverse solutions, without need for specific buffering components. Exploring experimental differences in sample preparation and imaging between these two studies, we suggest what may have led Hansen, Hendzel, and colleagues to mischaracterize the innate properties of chromatin condensates. We also describe how liquid-like in vitro behaviors can translate to the locally dynamic but globally constrained movement of chromatin in cells.
The systematic assessment of completeness of public metadata accompanying omics studies
Authors: Huang Yu-Ning , Jaiswal Pooja Vinod , Rajesh Anushka , Yadav Anushka , Yu Dottie , Liu Fangyun , Scheg Grace , Boldirev Grigore , Nakashidze Irina , Sarkar Aditya , Mehta Jay Himanshu , Wang Ke , Patel Khooshbu Kantibhai , Mirza Mustafa Ali Baig , Hapani Kunali Chetan , Peng Qiushi , Ayyala Ram , Guo Ruiwei , Kapur Shaunak , Ramesh Tejasvene , Abedalthagafi Malak S. , Mangul Serghei 
Published: November 2021

AbstractRecent advances in high-throughput sequencing technologies have made it possible to collect and share a massive amount of omics data, along with its associated metadata. Enhancing metadata availability is critical to ensure data reusability and reproducibility and to facilitate novel biomedical discoveries through effective data reuse. Yet, incomplete metadata accompanying public omics data limits the reproducibility and reusability of millions of omics samples. In this study, we performed a comprehensive assessment of metadata completeness shared in both scientific publications and/or public repositories by analyzing over 253 studies encompassing over 164 thousands samples. We observed that studies often omit over a quarter of important phenotypes, with an average of only 74.8% of them shared either in the text of publication or the corresponding repository. Notably, public repositories alone contained 62% of the metadata, surpassing the textual content of publications by 3.5%. Only 11.5% of studies completely shared all phenotypes, while 37.9% shared less than 40% of the phenotypes. Studies involving non-human samples were more likely to share metadata than studies involving human samples. We observed similar results on the extended dataset spanning 2.1 million samples across over 61,000 studies from the Gene Expression Omnibus repository. The limited availability of metadata reported in our study emphasizes the necessity for improved metadata sharing practices and standardized reporting. Finally, we discuss the numerous benefits of improving the availability and quality of metadata to the scientific community abd beyond, supporting data-driven decision-making and policy development in the field of biomedical research.