bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurocomputational mechanisms of affected beliefs
Authors: Müller-Pinzler Laura , Czekalla Nora , Mayer Annalina V , Schröder Alexander , Stolz David S , Paulus Frieder M , Krach Sören 
Published: October 2021

SummaryThe feedback people receive on their behavior shapes the process of belief formation and self-efficacy in mastering a given task. However, the neural and computational mechanisms of how the subjective value of these beliefs, and the corresponding affect, bias the learning process remain unclear. We investigated these mechanisms during the learning of self-efficacy beliefs using fMRI, pupillometry, and computational modeling, and by analyzing individual differences in affective experience. Biases in the formation of self-efficacy beliefs were associated with affect, pupil dilation, and neural activity within the anterior insula, amygdala, ventral tegmental area/ substantia nigra, and mPFC. Specifically, neural and pupil responses map the valence of the prediction errors in correspondence with individuals’ experienced affect and learning bias during belief formation. Together with the functional connectivity dynamics of the anterior insula within this network, our results hint at neural and computational mechanisms that integrate affect into the process of belief formation.
Multi-label topic classification for COVID-19 literature annotation using an ensemble model based on PubMedBERT
Authors: Tian Shubo , Zhang Jinfeng 
Published: October 2021

AbstractThe BioCreative VII Track 5 calls for participants to tackle the multi-label classification task for automated topic annotation of COVID-19 literature. In our participation, we evaluated several deep learning models built on PubMedBERT, a pre-trained language model, with different strategies addressing the challenges of the task. Specifically, multi-instance learning was used to deal with the large variation in the lengths of the articles, and focal loss function was used to address the imbalance in the distribution of different topics. We found that the ensemble model performed the best among all the models we have tested. Test results of our submissions showed that our approach was able to achieve satisfactory performance with an F1 score of 0.9247, which is significantly better than the baseline model (F1 score: 0.8678) and the mean of all the submissions (F1 score: 0.8931).
Differential Vulnerability of Anterior Cingulate Cortex Cell-Types to Diseases and Drugs
Authors: Smail Marissa A. , Chandrasena Sapuni S. , Zhang Xiaolu , Reddy Vineet , Kelley Craig , Herman James P. , Sherif Mohamed , McCullumsmith Robert E. , Shukla Rammohan 
Published: October 2021

ABSTRACTIn psychiatric disorders, mismatches between disease-states and therapeutic strategies are highly pronounced, largely because of unanswered questions regarding specific vulnerabilities of different cell-types and therapeutic responses. Which cellular events (housekeeping or salient) are most affected? Which cell-types succumb first to challenges, and which exhibit the strongest response to drugs? Are these events coordinated between cell-types? How does the disease-state and drug affect this coordination? To address these questions, we analyzed single-nucleus-RNAseq (sn-RNAseq) data from the human anterior cingulate cortex—a region involved in many psychiatric disorders. Density index, a metric for quantifying similarities and dissimilarities across functional profiles, was employed to identify common (housekeeping) or salient functional themes across all cell-types. Cell-specific signatures were integrated with existing disease and drug-specific signatures to determine cell-type-specific vulnerabilities, druggabilities, and responsiveness. Clustering of functional profiles revealed cell-types jointly participating in these events. SST and VIP interneurons were found to be most vulnerable, whereas pyramidal neurons were least vulnerable. Overall, the disease-state is superficial layer-centric, largely influences cell-specific salient themes, strongly impacts disinhibitory neurons, and influences astrocyte interaction with a subset of deep-layer pyramidal neurons. Drug activities, on the other hand, are deep layer-centric and involve activating a distinct subset of deep-layer pyramidal neurons to circumvent the disinhibitory circuit malfunctioning in the disease-state. These findings demonstrate a novel application of sn-RNAseq data to explain drug and disease action at a systems level, suggests a targeted drug development and reevaluate various postmortem-based findings.
Ormyrus labotus Walker (Hymenoptera: Ormyridae): another generalist that should not be a generalist is not a generalist
Authors: Sheikh Sofia I. , Ward Anna K.G. , Zhang Y. Miles , Davis Charles K. , Zhang Linyi , Egan Scott P. , Forbes Andrew A. 
Published: October 2021

AbstractSeveral recent reappraisals of supposed generalist parasite species have revealed hidden complexes of species, each with considerably narrower host ranges. Parasitic wasps that attack gall-forming insects on plants have life history strategies that are thought to promote specialization, and though many species are indeed highly specialized, others have been described as generalist parasites. Ormyrus labotus Walker (Hymenoptera: Ormyridae) is one such apparent generalist, with rearing records spanning more than 65 host galls associated with a diverse set of oak tree species and plant tissues. We pair a molecular approach with morphology, host ecology, and phenological data from across a wide geographic sample to test the hypothesis that this supposed generalist is actually a complex of several more specialized species. We find 16–18 putative species within the morphological species O. labotus, each reared from only 1–6 host gall types, though we identify no single unifying axis of specialization. We also find cryptic habitat specialists within two other named Ormyrus species. Our study suggests that caution should be applied when considering host ranges of parasitic insects described solely by morphological traits, particularly given their importance as biocontrol organisms and their role in biodiversity and evolutionary studies.
Extrinsic motivators drive children’s cooperation to conserve forests
Authors: Bowie Aleah , Tan Jingzhi , Zhou Wen , White Philip , Stoinski Tara , Su Yanjie , Hare Brian 
Published: October 2021

AbstractForests are essential common-pool resources. It is increasingly critical to nurture a lifelong concern for forest health both locally and globally. Here, in two experiments, we demonstrate that school age children (6-18 yrs. old; N>1000;) of three nationalities (China, D. R. Congo and U.S.) do not have levels of intrinsic motivation to allow for successful cooperation in common-pool goods games requiring them to maintain a forest. We instead find that the size, timing, and certainty of receiving individual payoffs from cooperation significantly boost the odds of successful conservation efforts. We also provide evidence that the experience of playing this game increases longer term motivation to conserve forests. Results have implications for designing policy and curriculum to encourage collective action for forest conservation.One Sentence SummaryExtrinsic motivation boosts concern for forests among children and adolescents in the United States, China, and the Democratic Republic of the Congo.
Categorization of prophage genes in Bacillus subtilis 168 and assessing their relative importance through RNA-seq gene expression analysis
Authors: Ng Wenfa 
Published: October 2021

AbstractBacteriophage evolves to control the population of fast-growing bacterial cells, without which explosion in bacterial population may induce unimaginable harm to diverse ecosystems. But, bacteriophage also “hide” in bacterial genomes when nutritional and environmental circumstances are unfavourable. This involves the integration of phage genome into the host genome at appropriate genomic loci in a process known as lysogeny. This work sought to delineate the prophages present in the annotated genome of Bacillus subtilis 168, and assess their relative importance through RNA-seq expression analysis. Firstly, examination of the annotated genome of the model Gram-positive bacterium revealed five distinct prophage regions: SPBeta, prophage 6, PBSX, prophage 3 region, and prophage 1 region. All prophage regions contain host genes, which suggests that host transposase activity have swapped in host genes for phage genes in the prophage genome. Given the significant number of phage genes that have been swapped into each of the prophage genome, all prophage regions are deemed to be defective. BLAST analysis further highlighted that many of the prophages in B. subtilis are extinct given that they do not have ancestral or daughter brethren. However, RNA-seq transcriptome analysis of B. subtilis turned out an interesting paradox indicative of the important role that host transposase have in swapping in host promoters for prophage genes. Specifically, a significant number of prophage genes are highly expressed, which is implausible given that phage genes should be transcriptionally silent. The result and phenomenon further suggests the relative facile nature in which host promoters could be swapped in for phage genes, which is indicative of presence of genomic motifs in prophage genome recognizable by host transposase. Existence of such sequence motifs is thus indicative of possible co-evolution of transposase and phages where transposases were originally a part of the phage genome, which latter “jumped out” into the host genome to aid the swapping in of host genes into the prophage genome for augmenting prophage genetic repertoire in the face of changing environmental conditions. Overall, it is not uncommon for bacterial species to harbour multiple prophages. But, lysogeny may not be a viable option for long-term preservation of prophage genetic repertoire given that host transposase would inevitable swap in host genes at random locations in the prophage genome.
A hyper-immunogenic and slow-growing fungal strain induces a murine granulomatous response to cryptococcal infection
Authors: Telzrow Calla L. , Righi Shannon Esher , Castro-Lopez Natalia , Campuzano Althea , Brooks Jacob T. , Carney John M. , Wormley Floyd L. , Alspaugh J. Andrew 
Published: October 2021

ABSTRACTMany successful pathogens cause latent infections, remaining dormant within the host for years but retaining the ability to reactivate to cause symptomatic disease. The human opportunistic pathogen Cryptococcus neoformans is a ubiquitous yeast that establishes latent pulmonary infections in immunocompetent individuals upon fungal inhalation from the environment. These latent infections are frequently characterized by granulomas, or foci of chronic inflammation, that contain dormant cryptococcal cells. Immunosuppression causes these granulomas to break down and release viable fungal cells that proliferate, disseminate, and eventually cause lethal cryptococcosis. This course of C. neoformans dormancy and reactivation is understudied due to limited models, as chronic pulmonary granulomas do not typically form in most mouse models of cryptococcal infection. Here, we report that a previously characterized Cryptococcus-specific gene which is required for host-induced cell wall remodeling, MAR1, inhibits murine granuloma formation. Specifically, the mar1Δ loss-of-function mutant strain induces mature pulmonary granulomas at sites of infection dormancy in mice. Our data suggest that the combination of reduced fungal burden and increased immunogenicity of the mar1Δ mutant strain stimulates a host immune response that contains viable fungi within granulomas. Furthermore, we find that the mar1Δ mutant strain has slow growth and hypoxia resistance phenotypes, which may enable fungal persistence within pulmonary granulomas. Together with the conventional primary murine infection model, latent murine infection models will advance our understanding of cryptococcal disease progression and define fungal features important for persistence in the human host.
Intrahost-diversity of influenza A virus in upper and lower respiratory tract derived samples from a college community
Authors: Sapoval Nicolae , de Mesquita P. Jacob Bueno , Liu Yunxi , Wang Roger , Liu Tian Rui , Garza Josie , Williams Torrey , Cadiz Carmelli , Tan Gene S. , Van Bakel Harm , Elworth R. A. Leo , Grantham Michael L. ,   EMIT Investigators, Milton Donald K. , Treangen Todd J. 
Published: October 2021

ABSTRACTMotivationInfluenza is a rapidly mutating RNA virus responsible for annual epidemics causing substantial morbidity, mortality, and economic loss. Characterizing influenza virus mutational diversity and evolutionary processes within and between human hosts can provide tools to help track and understand transmission events. In this study we investigated possible differences between the intrahost genomic content of influenza virus in upper respiratory swabs and exhaled aerosols thought to be enriched for virus from the lower respiratory tract.ResultsWe examined the sequences of specimens collected from influenza A virus (IAV) infected college community members from December 2012 through May 2013. We analyzed four types of IAV samples (fine ≤5 µm aerosols (N=38), coarse >5µm aerosols (N=27), nasopharyngeal (N=53), and oropharyngeal swabs (N=47)) collected from 42 study participants with 60 sampling instances. Eighteen (42.9%) participants had data from four sample types (nasopharyngeal swab, oropharyngeal swab, coarse aerosol, fine aerosol) included in the analysis, 10 (23.8%) had data from 3 sample types, 10 (23.8%) had data from 2 sample types, and 4 (9.5%) had data from one type of sample included in the analysis. We found that 481 (53.3%) consensus single nucleotide polymorphisms are shared by all sample types and 600 (66.5%) are shared by at least three different sample types. We observed that within a single patient consensus and non-consensus single nucleotide variants are shared across all sample types. Finally, we inferred a phylogenetic tree using consensus sequences and found that samples derived from a single patient are monophyletic.ConclusionsSingle nucleotide polymorphisms did not differentiate between samples with varying origin along the respiratory tree. We found that signatures of variation in non-consensus intrahost single nucleotide variants are host and sample, but not site specific. We conclude that the genomic information available does not allow us to discern a transmission route. Future investigation into whether any site-specific mutational signatures emerge over a longer period of infection, for example in immunocompromised hosts, can be interesting from the virus evolution perspective.
Signal Intensity Normalization of Multispectal Magnetic Resonance Images Obtained with Clinical Sequences
Authors: Brier Matthew R. , Xiang Biao , Li Zhuocheng , Naismith Robert T. , Yablonskiy Dmitriy , Cross Anne H. , Benzinger Tammie L. S. , Snyder Abraham Z. 
Published: October 2021

AbstractAssessment of intrinsic tissue integrity is commonly accomplished via quantitative relaxometry or other specialized imaging, which requires sequences and analysis procedures not routinely available in clinical settings. We detail an alternative technique for extraction of quantitative tissue biomarkers based on intensity normalization of T1- and T2-weighted images. We develop the theoretical underpinnings of this approach and demonstrate its utility in imaging of multiple sclerosis.
RNA sensing via LGP2 is essential for the induction of a type I IFN response in ADAR1 deficiency
Authors: Stok Jorn E. , Oosenbrug Timo , ter Haar Laurens R. , Gravekamp Dennis , Bromley Christian P. , Zelenay Santiago , Reis e Sousa Caetano , van der Veen Annemarthe G. 
Published: October 2021

AbstractRNA editing by the enzyme Adenosine Deaminase Acting on RNA 1 (ADAR1) is an important mechanism by which cells avoid innate immune responses to some endogenous RNAs. In ADAR1-deficient cells, unedited self RNAs can form base-paired structures that resemble viral RNAs and inadvertently activate antiviral innate immune pathways that lead to the induction of type I interferon (IFN). Rare mutations in ADAR1 cause Aicardi-Goutières Syndrome (AGS), a severe childhood autoinflammatory syndrome that is characterized by chronic and excessive type I IFN production and developmental delay. Conversely, ADAR1 dysfunction and consequent type I IFN production helps restrict tumor growth and potentiates the activity of some chemotherapy drugs. Induction of type I IFN in ADAR1-deficient cells is thought to be due to triggering of the cytosolic RIG-I-like receptor (RLR), MDA5, by unedited self RNAs. Here, we show that another RLR, LGP2, also has an essential role. We demonstrate that ADAR1-deficient human cells fail to mount a type I IFN response in the absence of LGP2 and this involves the canonical function of LGP2 as an RNA sensor and facilitator of MDA5-dependent signaling. Further, we show that the sensitivity of tumor cells to ADAR1 loss requires the presence of LGP2. Finally, we find that type I IFN induction in tumor cells depleted of ADAR1 and treated with some chemotherapeutics is fully dependent on the expression of LGP2. These findings highlight a central role for LGP2 in self RNA sensing with important clinical implications for the treatment of AGS as well as for the potential application of ADAR1-directed anti-tumor therapy.
Hand and face somatotopy shown using MRI-safe vibrotactile stimulation with a novel Soft Pneumatic Actuator (SPA)-Skin interface
Authors: Kikkert Sanne , Sonar Harshal A. , Freund Patrick , Paik Jamie , Wenderoth Nicole 
Published: October 2021

AbstractThe exact somatotopy of the human facial representation in the primary somatosensory cortex (S1) remains debated. One reason that progress has been hampered is due to the methodological challenge of how to apply automated vibrotactile stimuli to face areas in a manner that is: 1) reliable despite differences in the curvatures of face locations; and 2) MR-compatible and free of MR-interference artefacts when applied in the MR head-coil. Here we overcome this challenge by using soft pneumatic actuator (SPA) technology. SPAs are made of a soft silicon material and can be in- or deflated by means of airflow, have a small diameter, and are flexible in structure, enabling good skin contact even on curved body surfaces (as on the face). To validate our approach, we first mapped the well-characterised S1 finger layout using this novel device and confirmed that tactile stimulation of the fingers elicited characteristic somatotopic finger activations in S1. We then used the device to automatically and systematically deliver somatosensory stimulation to different face locations. We found that the forehead representation was least distant from the representation of the hand. Within the face representation, we found that the lip representation is most distant from the forehead representation, with the chin represented in between. Together, our results demonstrate that this novel MR compatible device produces robust and clear somatotopic representational patterns using vibrotactile stimulation through SPA-technology.
Cancer/Testis genes are predictive of breast tumor subtypes
Authors: Laisné Marthe , Benlamara Sarah , Nicolas André , Djerroudi Lounes , Gupta Nikhil , Daher Diana , Ferry Laure , Kirsh Olivier , Philippe Claude , Okada Yuki , Cristofari Gael , Meseure Didier , Vincent-Salomon Anne , Ginestier Christophe , Defossez Pierre-Antoine 
Published: October 2021

AbstractBreast cancer is the most prevalent type of cancer in women worldwide. Within breast tumors, the basal-like subtype has the worst prognosis and no dedicated therapy, therefore new tools to understand, detect, and treat these tumors are needed. Certain germline genes are re-expressed in tumors, and constitute the Cancer/Testis genes; their misexpression has diagnostic and therapeutic applications. Here, we designed a new approach to examine Cancer/ Testis gene misexpression in breast tumors. We identify several new markers in Luminal and HER-2 positive tumors, some of which predict response to chemotherapy. We then use machine learning to identify the 2 Cancer/Testis genes most associated with basal-like breast tumors: HORMAD1 and CT83. We show that these genes are expressed by tumor cells but not the microenvironment, and that they are not expressed by normal breast progenitors, in other words their activation occurs de novo. We find these genes are epigenetically repressed by DNA methylation, and that their activation upon DNA demethylation is irreversible, providing a memory of past epigenetic disturbances. Basal-like tumors expressing both genes have a poorer outcome than tumors expressing either gene alone or neither gene. Therefore, these findings suggest a potential synergistic effect between Cancer/Testis genes in basal breast tumors; these findings have consequences for the understanding, diagnosis, and therapy of the breast tumors with the worse outcomes.
First evidence towards chemical self-recognition in a gecko
Authors: Szabo Birgit , Ringler Eva 
Published: October 2021

AbstractSelf-recognition is the ability to recognise stimuli originating from oneself. Humans and most great apes show evidence of true self-recognition in the mirror test. They use their reflection to remove a mark that is only visible in the mirror. Not all animals, however, rely primarily on vision. In lizards, chemical cues are important in social interactions. A number of lizard species show chemical self-recognition but it has never been investigated in a gecko species. Here, we test the tokay gecko (Gekko gecko) a territorial species with parental care on their ability to discriminate their own skin and faecal chemicals from those of same-sex, unfamiliar conspecifics. Geckos show a higher response rate towards chemicals from unfamiliar individuals compared to self-produced chemicals and a water control. Lizards showed self-directed behaviour, responded stronger to skin chemicals and females responded more than males. Our study provides first evidence towards self-recognition and for a social function of chemical present on faeces in tokay geckos but further tests are needed to confirm true self-recognition. Tokay geckos are an excellent model species to investigate individual recognition to demonstrate more sophisticated social cognitive abilities than have previously been attributed to reptiles.