bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reverse Correlation Uncovers More Complete Tinnitus Spectra
Authors: Hoyland Alec , Barnett Nelson V. , Roop Benjamin W. , Alexandrou Danae , Caplan Myah , Mills Jacob , Parrell Benjamin , Chari Divya A. , Lammert Adam C. 
Published: December 2022

AbstractGoalThis study validates an approach to characterizing the sounds experienced by tinnitus patients via reverse correlation, with potential for characterizing a wider range of sounds than currently possible.MethodsTen normal-hearing subjects assessed the subjective similarity of random auditory stimuli and target tinnitus-like sounds (“buzzing” and “roaring”). Reconstructions of the targets were obtained by regressing subject responses on the stimuli, and were compared for accuracy to the frequency spectra of the targets using Pearson’sr.ResultsReconstruction accuracy was significantly higher than chance across subjects: buzzing (M= 0.53,SD= 0.27):t(9) = 5.766,p <0.001; roaring (M= 0.57,SD= 0.30):t(9) = 5.76,p <0.001.ConclusionReverse correlation can accurately reconstruct nontonal tinnitus-like sounds in normal-hearing subjects, indicating its potential for characterizing the sounds experienced by patients with non-tonal tinnitus.Impact StatementCharacterization of tinnitus sounds can inform treatment by facilitating individualized sound therapies, leading to better outcomes for patients suffering from the cognitive and psychological effects of tinnitus.
GDF15 Is Required for Cold-Induced Thermogenesis and Contributes to Improve Systemic Metabolic Health Following Loss of OPA1 in Brown Adipocytes
Authors: Jena Jayashree , García-Peña Luis Miguel , Weatherford Eric T. , Marti Alex , Bjorkman Sarah H. , Kato Kevin , Koneru Jivan , Chen Jason , Seeley Randy J. , Abel E. Dale , Pereira Renata O. 
Published: December 2022

AbstractPreviously we showed that mice lacking the protein optic atrophy 1 (OPA1 BKO) in brown adipose tissue (BAT) have induction of the activating transcription factor 4 (ATF4), which promotes fibroblast growth factor 21 (FGF21) secretion as a batokine. FGF21 increases metabolic rates at baseline conditions but is dispensable for the resistance to diet-induced obesity (DIO) reported in OPA1 BKO mice [1]. To determine alternative mediators of this phenotype, we performed transcriptome analysis, which revealed increased levels of growth differentiation factor 15 (GDF15) in BAT. To determine if ATF4 induction was mediated by the protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), and to evaluate the contribution of GDF15 to the resistance to DIO, we selectively deleted PERK or GDF15 in OPA1 BKO mice. Mice lacking both OPA1 and PERK in BAT had preserved induction of ATF4. Importantly, simultaneous deletion of OPA1 and GDF15 partially reversed the resistance to diet-induced obesity and abrogated the improvements in glucose tolerance. Furthermore, GDF15 mediated cold-induced thermogenesis, likely via sympathetic activation of iWAT. Taken together, our data indicate that PERK is dispensable for ATF4 induction, but GDF15 contributes to the resistance to DIO, and is required for glucose homeostasis and thermoregulation in OPA1 BKO mice.
Lack of evidence supporting transgenerational effects of non-transmitted paternal alleles on the murine transcriptome
Authors: Gularte-Mérida Rodrigo , Charlier Carole , Georges Michel 
Published: December 2022

AbstractTransgenerational genetic effects are defined as the effects of untransmitted parental alleles on the phenotype of their offspring. Well-known transgenerational genetic effects, in humans and other mammals, are the effects of a parental genotype on the nurturing ability of the parents, coined “genetic nurture”. However, there exist examples of transgenerational genetic effects in model organisms that are independent of nurturing effects and support the epigenetic transmission of a memory of the parental genotype possibly mediated by small RNA species. To test whether such transgenerational epigenetic effects might exist in mammals, we generated 833 isogenic C57BL/6J (B6) mice that differed only by the presence in the genome of their sire of one copy of four A/J chromosomes (MMU 15, 17, 19 or X). We measured 25 anatomical traits and performed RNA-Seq on five distinct tissues (heart, liver, pituitary, whole embryo, and placenta). There was no evidence of a significant effect from untransmitted A/J sire chromosome alleles, whether on anatomical traits or gene expression level. We observed an effect onMid1expression levels in multiple tissues, but this was shown to be due to a de novo mutation that occurred in one of the sire lines. We conclude that transgenerational epigenetic memory of non-transmitted paternal alleles - if it exists - is uncommon in mice and likely other mammals.
(Epi)mutation rates and the evolution of composite trait architectures
Authors: Polizzi Bastien , Calvez Vincent , Charlat Sylvain , Rajon Etienne 
Published: December 2022

AbstractMutation rates vary widely along genomes and across inheritance systems. This suggests that complex traits – resulting from the contributions of multiple determinants – might be composite in terms of the underlying mutation rates. Here we investigate through mathematical modeling whether such an heterogeneity may drive changes in a trait’s architecture, especially in fluctuating environments where phenotypic instability can be beneficial. We first identify a convexity principle, related to the shape of the trait’s fitness function, setting conditions under which composite architectures should be adaptive or, conversely and more commonly, should be selected against. Simulations reveal, however, that applying this principle to realistic evolving populations requires taking into account pervasive epistatic interactions that take place in the system. Indeed, the fate of a mutation affecting the architecture depends on the (epi)genetic background, itself depending upon the current architecture in the population. We tackle this problem by borrowing the adaptive dynamics framework from evolutionary ecology – where it is routinely used to deal with such resident/mutant dependencies – and find that the principle excluding composite architectures generally prevails. Yet, the predicted evolutionary trajectories will typically depend on the initial architecture, possibly resulting in historical contingencies. Finally, by relaxing the large population size assumption, we unexpectedly find that not only the strength of selection on a trait’s architecture, but also its direction, depend on population size, revealing a new occurrence of the recently coined phenomenon of ‘sign inversion’.
Multiple NTS Neuron Populations Synergistically Suppress Physiologic Food Intake but are Dispensable for the Response to VSG
Authors: Qui Weiwei , Hutch Chelsea R. , Wang Yi , Wloszek Jennifer , Rucker Rachel A. , Myers Martin G. , Sandoval Darleen 
Published: December 2022

AbstractSeveral discrete groups of feeding-regulated neurons in thenucleus tractus solitarius(NTS) suppress food intake, including aversion-promoting neurons that expressCck(NTSCckcells) and distinctLepr- andCalcr-expressing neurons (NTSLeprand NTSCalcrcells, respectively) that suppress food intake without promoting aversion. To test synergies among these cell groups we manipulated multiple NTS cell populations simultaneously. We found that activating multiple sets of NTS neurons (e.g., NTSLeprplus NTSCalcr(NTSLC), or NTSLCplus NTSCck(NTSLCK)) suppressed feeding more robustly than activating single populations. While activating groups of cells that include NTSCckneurons promoted conditioned taste avoidance (CTA), NTSLCactivation produced no CTA despite abrogating feeding. Thus, the ability to promote CTA formation represents a dominant effect, but activating multiple non-aversive populations additively suppresses food intake without provoking aversion. Although silencing multiple NTS neuron groups augmented food intake and body weight more dramatically than silencing single populations, feeding activated many non-NTSLCKneurons and silencing NTSLCKneurons failed to blunt the weight loss response to vertical sleeve gastrectomy (VSG). Hence, while each of these NTS neuron populations plays crucial and additive roles in the control of energy balance, as-yet undefined cell types must make additional contributions to the control of feeding and the response to VSG.
Cx26 heterozygous mutations cause hyperacusis-like hearing sensitivity enhancement and increase susceptibility to noise
Authors: Liu Li-Man , Liang Chun , Chen Jin , Fang Shu , Zhao Hong-Bo 
Published: December 2022

AbstractGap junction geneGJB2(Cx26) mutations cause >50% of nonsyndromic hearing loss. Its recessive hetero-mutation carriers, who have no deafness, occupy ∼10-20% of the general population. Here, we report an unexpected finding that these heterozygote carriers have hearing over-sensitivity and active cochlear amplification increased. Mouse models show that Cx26 hetero-deletion reduced endocochlear potential (EP) generation in the cochlear lateral wall and caused outer hair cell electromotor protein prestin compensatively upregulated to increase active cochlear amplification and hearing sensitivity. The increase of active cochlear amplification also increased sensitivity to noise; exposure of daily-level noise could cause Cx26+/-mice permanent hearing threshold shift leading to hearing loss. This study demonstrate that Cx26 recessive heterozygous mutations are not ‘harmless’ for hearing as previously considered and can cause hyperacusis-like hearing over-sensitivity. The data also indicate thatGJB2hetero-mutation carriers are vulnerable to noise and should avoid noise exposure in daily-life.TeaserCx26 hetero-mutations are not harmless and can cause hearing over-sensitivity and increase susceptibility to noise.
Application of Machine Learning and Virtual Reality for Volumetric Analysis of Arterial Lesions
Authors: Cartaya Ana E. , Maiocchi Sophie , Buglak Nicholas E. , Torzone Sarah , Messinger Geri , Bahnson Edward S. M. 
Published: December 2022

ABSTRACTCardiovascular disease (CVD) remains the leading cause of mortality worldwide. Preclinical studies to research and validate therapeutic interventions for CVD often depend on two- dimensional histological surveys. The use of light sheet fluorescence microscopy together with optical clearing methods amenable to immunofluorescence staining are recent advances, all of which deliver detailed three-dimensional rendering of vessels. This offers the ability to describe and quantify features critical in CVD models, specifically, atherosclerotic plaque burden in atherosclerotic animal models and neointimal hyperplasia in surgical models. The main challenge for this approach remains the lengthy, hands-on, analysis time. Labkit is a user- friendly Fiji plugin that applies a machine-learning algorithm to create 3D renderings from large microscopy data. Likewise, syGlass a virtual reality (VR) software, allows for 3D visualization and analysis of information-rich image datasets. The application of these tools is expected to decrease the hands-on analysis time required to generate accurate volumetric renderings of arterial disease and injury features in animal models of CVD. For atherosclerotic burden analysis, Ldlr−/−(C57/BL6) mice aged 6-8 weeks were fed a high-fat diet for 15 weeks to allow the development of atherosclerotic plaque along the aorta. For neointimal hyperplasia analysis, surgically intervened carotid arteries from rats and mice were collected 2 weeks post-surgery. iDISCO+ or AdipoClear and immunolabeling together with light-sheet fluorescence microscopy allowed for three-dimensional visualization of the vessels. Both Imaris software v9.9.1 and the built-in bridge to ImageJ/Labkit were used to quantify plaque burden and neointimal hyperplasia manually or automatically. syGlass was also utilized for the quantification of plaque burden and other disease-associated characteristics. Our findings indicate that both Labkit and syGlass offer effective and user-friendly platforms for the segmentation of atherosclerotic plaque and/or neointimal hyperplasia in animal models.
Tactile Stimulation Designs Adapted to Clinical Settings Result in Reliable fMRI-based Somatosensory Digit Maps
Authors: Steinbach Till , Eck Judith , Timmers Inge , Biggs Emma , Goebel Rainer , Schweizer Renate , Kaas Amanda 
Published: December 2022

ABSTRACTA wide range of neurological diseases with impaired motor functioning of the upper extremities are accompanied by impairments of somatosensory functioning, which are often undescribed but can provide crucial information for diagnostics, treatment selection, and follow-up. Therefore, a reliable description of the functional representation of the digits in the somatosensory cortex would be a highly valuable, but currently lacking, tool in the clinical context. Task-based functional Magnetic Resonance Imaging of passive tactile stimulation provides an indirect, but valid description of the layout of the digit map in the primary somatosensory cortex. However, to fulfill the specific requirements for clinical application, the presently established approaches need to be adapted and subsequently assessed for feasibility and retest reliability, in order to provide informative parameters for the description of the evoked digit activations. Accordingly, the present high-field 3T fMRI study compares the performance of two established digit mapping designs - travelling wave (TW) and blocked design (BD) - for passive tactile stimulation of the five digits, adapted to reduce the time requirements to just below 15 minutes. To be able to assess the retest reliability unaffected by any clinical conditions, the study was performed on neurotypical participants. The results show that both stimulation designs evoke significant and distinct activation clusters in the primary somatosensory cortex of all participants for all five digits. The average spatial locations of the center of gravities across participants show the common succession of distinct digit representation along the central sulcus. The cortical extent elicited activation, which is generally larger for the thumb and the index finger, also shows comparable average values across the two approaches. Less overlap of activation between neighboring digits was obtained in BD, consistent with the distinct single digit neuronal representations. A high retest reliability was obtained for the location of the digit activation, displaying stable center of gravity locations across sessions for both stimulation designs. This is contrasted by only medium to low retest reliability for the extent and overlap of the digit activations, indicating discrepancies across sessions. These results demonstrate the capacity of shortened fMRI digit mapping approaches (both TW and BD) to obtain the full layout of single digit cortical activations on the level of the individual, which together with the high reliability of the location of the digit representation over time indicates both approaches are clinically applicable.
Biomimetic human lung alveolar interstitium chip with extended longevity
Authors: Man Kun , Liu Jiafeng , Liang Cindy , Corona Christopher , Story Michael D. , Meckes Brian , Yang Yong 
Published: December 2022

AbstractDetermining the mechanistic causes of lung diseases, developing new treatments thereof, and assessing toxicity whether from chemical exposures or engineered nanomaterials would benefit significantly from a preclinical human lung alveolar interstitium model of physiological relevance. The existing preclinical models have limitations because they fail to replicate the key anatomical and physiological characteristics of human alveoli. Thus, a human lung alveolar interstitium chip was developed to imitate key alveolar microenvironmental factors including: an electrospun nanofibrous membrane as the analogue of the basement membrane for co-culture of epithelial cells with fibroblasts embedded in 3D collagenous gels; physiologically relevant interstitial matrix stiffness; interstitial fluid flow; and 3D breathing-like mechanical stretch. The biomimetic chip substantially improved epithelial barrier function compared to transwell models. Moreover, the chip having a gel made of a collagen I-fibrin blend as the interstitial matrix sustained the interstitium integrity and further enhanced the epithelial barrier resulting in a longevity that extended beyond eight weeks. The assessment of multiwalled carbon nanotube toxicity on the chip was in line with the animal study.
HydRA: Deep-learning models for predicting RNA-binding capacity from protein interaction association context and protein sequence
Authors: Jin Wenhao , Brannan Kristopher W. , Kapeli Katannya , Park Samuel S. , Tan Hui Qing , Gosztyla Maya L. , Mujumdar Mayuresh , Ahdout Joshua , Henroid Bryce , Rothamel Katherine , Xiang Joy S. , Wong Limsoon , Yeo Gene W. 
Published: December 2022

AbstractRNA-binding proteins (RBPs) control RNA metabolism to orchestrate gene expression, and dysfunctional RBPs underlie many human diseases. Proteome-wide discovery efforts predict thousands of novel RBPs, many of which lack canonical RNA-binding domains. Here, we present a hybrid ensemble RBP classifier (HydRA) that leverages information from both intermolecular protein interactions and internal protein sequence patterns to predict RNA-binding capacity with unparalleled specificity and sensitivity using support vector machine, convolutional neural networks and transformer-based protein language models. HydRA enables Occlusion Mapping to robustly detect known RNA-binding domains and to predict hundreds of uncharacterized RNA-binding domains. Enhanced CLIP validation for a diverse collection of RBP candidates reveals genome-wide targets and confirms RNA-binding activity for HydRA-predicted domains. The HydRA computational framework accelerates construction of a comprehensive RBP catalogue and expands the set of known RNA-binding protein domains.HighlightsHydRA combines protein-protein interaction and amino acid sequence information to predict RNA binding activity for 1,487 candidate genes.HydRA predicts RNA binding with higher specificity and sensitivity than current approaches, notably for RBPs without well-defined RNA-binding domains.Occlusion Mapping with HydRA enables RNA-binding domain discovery.Enhanced CLIP confirms HydRA RBP predictions with RNA-binding domain resolution.
Enhancing female status by improving nutrition: the role of corporate social responsibility in Nigeria’s oil region
Authors: Uduji Joseph Ikechukwu , Okolo-Obasi Nduka Elda Nduka 
Published: December 2022

Purpose
The purpose of this paper is to critically examine the multinational oil companies’ (MOCs) corporate social responsibility (CSR) initiatives in Nigeria. Its special focus is to investigate the impact of the global memorandum of understanding (GMoU) on improving female status by improving nutrition in the Niger Delta region of Nigeria.

Design/methodology/approach
This paper adopts a survey research technique, aimed at gathering information from a representative sample of the population, as it is essentially cross-sectional, describing and interpreting the current situation. A total of 768 women respondents were sampled across the rural areas of the Niger Delta region.

Findings
The results from the use of a combined propensity score matching and logit model indicate that GMoU model has made significant impact in the key areas of assessment – gender-sensitive nutrition education, food security at household level, reduction on food taboos and female access to education.

Practical implications
This suggests that CSR interventions targeting to improve the nutrition status of girls and adolescents will help to ensure that female’s status improves throughout the life circle in the region.

Social implications
This implies that MOCs’ investment in the nutrition of female is an important short-term barometer in assessing expected returns to improving household nutrition and overall human development capacity for sub-Saharan Africa.

Originality/value
This research contributes to the inequality debate in the women’s nutrition and inclusive growth literature from the CSR perspective. It concludes that business has an obligation to help in solving problems of public concern.
Social media discussion forums, home country and immigrant consumer acculturation: the case of Iranian immigrants in Australia
Authors: Sepehr Sorush , Carlson Jamie , Rosenberger III Philip , Pandit Ameet 
Published: December 2022

PurposeSocial media has transformed communication possibilities for immigrant consumers with their home country in their acculturation efforts. However, the acculturative outcomes of consumer interactions with the home country through social media are largely overlooked in previous research. This study aims to investigate the acculturative processes and outcomes resulting from interacting with the home country through social media.Design/methodology/approachA netnographic approach is used to collect data from a social media platform that provides an interactive social context in which Iranian immigrants in Australia share their experiences of immigration with non-immigrants who are considering and planning to migrate to Australia.FindingsFindings show how both immigrants and non-immigrant users via social media reflexively contribute to the formation of two competing collective narratives, namely, the dominant, romanticizing narrative and counter, pragmatic narratives. Findings highlight how notions of the home and host countries, and the idea of migrating from home to host, are constructed as the result of the circulation of the dominant and counter narratives. Further findings include how these two collective narratives come into play in the formation of three acculturative outcomes, namely, self-validating, ordinary experts and wellbeing. These insights extend consumer acculturation theory through highlighting the acculturative processes and outcomes of interactions with the home country via a social media platform. This includes, for example, how interacting with the home culture can take on assimilationist properties through the construction of a romanticized representation of the hosting society (i.e. Australia) in the dominant collective narrative.Practical implicationsImplications for ethnic marketing practice, policymakers and non-governmental organisations are advanced, especially regarding using social media as a channel to communicate with current and potential immigrant consumers. Notably, policymakers can use social media to engage with immigrants before and after migration to reduce the potential for cognitive dissonance in recent arrivals. Managerially, brands can advertise on Web-based forums, independent websites and social media platforms to target potential immigrants to sell relevant products immigrants needs after migrating to the host country.Social implicationsFindings broaden the understanding of the potential acculturative outcomes on social media by moving away from the traditional outcomes, which are restricted to the dichotomy between the home and host cultures.Originality/valueScholarly attention is deficient on the role of direct interaction with the home country in immigrant consumer acculturation, especially through social media, which is the focus of this study.