bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial genetics and bipolar disorder
Authors: Konradi Christine , Kato Tadafumi 
Published: March 2022

Abstract
Mitochondria play a central role in brain energy metabolism and brain health. Because the brain is uniquely dependent on mitochondria for its energy requirements, minor disruptions in mitochondrial function can lead to selective disturbances in affective networks. A number of observations have led to the insight that mitochondria play a role in mood disorders in at least a subset of individuals. Bona fide mitochondrial diseases have a high prevalence of mood disturbances and psychiatric conditions; mitochondria-related functions are abnormal in bipolar disorder; some mitochondrial DNA variants are associated with bipolar disorder; mitochondria-related gene expression is altered in bipolar disorder; and mood stabilizers also stabilize mitochondrial function. This chapter will delve into the intricacies of mitochondria and their function in the brain, and detail the various experimental conditions and findings that show the association of mitochondria and energy metabolism with bipolar and mood disorders.
Integration and consolidation
Authors: Strakowski Stephen M. , Malhi Gin S. 
Published: March 2022

AbstractIn this book, leading experts have provided comprehensive and current reviews of the current state of knowledge regarding how genomics and brain imaging are defining the etiology and expression of bipolar disorder. Taken together, this state of knowledge begins to define a model of illness that is discussed in this chapter. As a starting point, the symptoms of bipolar disorder suggest that the disruption in brain systems that manage emotional homeostasis and reward processing (i.e., behavioral activation) must be represented in any proposed models of illness. Moreover, the typical onset in youth and progressive course of illness suggest a developmental component that persists until a recurrent mood disorder is established. Supporting these assumptions, neuroimaging research has steadily defined disruption in key ventral prefrontal-striatal-thalamic networks that may define the functional neuroanatomy of this condition. Differences from typical neurodevelopment in the formation of these networks, perhaps due to underlying multigenetic causes, likely establishes this disruption. The specific genetic basis has remained elusive, although studies of genes, gene combinations, and epigenetic events, including mitochondrial control, appear to be contributing components. These models offer an opportunity for focused, hypothesis-driven testing to drive future investigations, hopefully identifying the causes of bipolar disorder and ultimately providing specific targets for improved treatments.
Hypomorphism of a novel long ERα isoform causes severe reproductive dysfunctions in female mice
Authors: Saito Kenji , Dickey Jacob E. , Rodeghiero Samuel R. , Toth Brandon A. , Kelly Matthew J. , Deng Yue , Singh Uday , Deng Guorui , Jiang Jingwei , Cui Huxing 
Published: March 2022

AbstractEstrogen receptor alpha (ERα)-mediated estrogen signaling play a pivotal role in both reproductive and non-reproductive functions. Transcriptional regulation of ERα gene is highly complex, with multiple transcript variants being differentially produced across the tissues. However, tissue-specific variation and physiological specificity of the ERα variants are not yet fully understood. In an attempt to generate a Cre-dependently restorable ERα-null mice for functional investigation of the genetic sufficiency, we unexpectedly produced ERα hypomorphic mice with biased downregulation of a previously unappreciated long ERα isoform that is enriched in the female reproductive organs (uterus and ovaries) and the pituitary but minimally expressed in the brain. Female homozygous mutant mice were capable of pregnancy but displayed irregular estrus cycle and rarely maintained alive newborns without significant morphological and pathological changes in reproductive system and the disruption of body weight homeostasis, indicating the vital role of this long isoform in female reproductive function. Collectively, our results define a tissue-specifically enriched long ERα isoform and its preferential role in female reproductive function over body weight homeostasis.
Service-user experiences of an integrated psychological intervention for depression or anxiety and tobacco smoking in IAPT: A qualitative investigation into mechanisms of change in quitting smoking
Authors: Fredman Stein Kim , Sawyer Katherine , Daryan Shadi , Allen Jennifer L , Taylor Gemma 
Published: March 2022

AbstractBackgroundHigh smoking prevalence leads to increased morbidity and mortality in individuals with depression/anxiety. Integrated interventions targeting both smoking and mood have been found to be more effective than those targeting smoking alone, but the mechanisms of change of these integrated interventions have not been investigated.AimsThis qualitative study aimed to investigate participants’ subjective experiences of the mechanisms underlying change in smoking behaviour following an integrated CBT-based intervention for smoking cessation and depression/anxiety.MethodsThis study was embedded within an ongoing randomised controlled acceptability and feasibility trial (http://www.isrctn.com/ISRCTN99531779). Semi-structured interviews were conducted with 15 IAPT service users and data were analysed using thematic analysis.ResultsFive themes were identified: (1) acquiring an increased awareness of smoking patterns, (2) developing individualised strategies, (3) practitioner style as “supportive but not lecture-y” (4) importance of regular sessions, and (5) having the opportunity to access intervention at “the right time”.ConclusionsThese findings further our understanding of the mechanisms of change towards smoking cessation in this integrated intervention and highlight the need to emphasise and embed these components in manualised interventions to optimise therapeutic benefits and reduce smoking prevalence in people with depression/anxiety.Relevance statementThis study qualitatively investigated mechanisms underlying change in smoking behaviour following an integrated intervention for depression/anxiety and smoking cessation. Research shows interventions integrating smoking cessation and mood management are more effective than smoking cessation interventions alone; however further investigation is needed to understand mechanisms of change for integrated interventions. The current results identified key factors that were important for participants in the integrated intervention to reduce smoking. An improved understanding of mechanisms underlying change in smoking behaviour helps to identify therapist characteristics and treatment components that improve therapeutic outcomes which future research could investigate using a randomised controlled trial design.
Inter-brain coupling reflects disciplinary differences in real-world classroom learning
Authors: Chen Jingjing , Qian Penghao , Gao Xinqiao , Li Baosong , Zhang Yu , Zhang Dan 
Published: March 2022

AbstractClassroom is the primary site for learning. One important feature of classroom learning is its organization into different disciplines. While disciplinary differences could substantially influence students’ learning processes, little is known about the neural mechanism underlying successful disciplinary learning. In the present study, wearable EEG devices were used to record a group of high school students during their classes of a soft (Chinese) and a hard (Math) discipline throughout one semester. The students with higher learning outcomes in Chinese were found to have better inter-brain neural couplings with their excellent peers, whereas the students with higher Math outcomes were found to have better couplings with the class average. Moreover, the inter-brain couplings showed distinct dominant frequencies for the two disciplines. Our results illustrate disciplinary differences in successful learning from an inter-brain perspective and suggest the neural activities of excellent peers and class average as exemplars for soft and hard disciplines.TeaserSuccessful classroom learning is associated with distinct inter-brain coupling patterns for soft and hard disciplines
In silicoInvestigation of Molecular Networks Linking Gastrointestinal Diseases, Malnutrition, and Sarcopenia
Authors: Hoch Matti , Ehlers Luise , Bannert Karen , Stanke Christina , Brauer David , Caton Vanessa , Lamprecht Georg , Wolkenhauer Olaf , Jaster Robert , Wolfien Markus 
Published: March 2022

AbstractMalnutrition is a common primary or secondary complication in gastrointestinal diseases. The patient’s nutritional status also influences muscle mass and function, which can be impaired up to the degree of sarcopenia. The molecular interactions in diseases leading to sarcopenia are complex and multifaceted, affecting muscle physiology, the intestine (nutrition), and the liver at different levels. Although extensive knowledge of individual molecular factors is available, their regulatory interplay is not yet fully understood. A comprehensive overall picture of pathological mechanisms and resulting phenotypes is lacking.In silicoapproaches that convert existing knowledge into computationally readable formats can help to unravel such complex systems. We compiled available experimental evidence for molecular interactions involved in the development of sarcopenia into a knowledge base, referred to as the Sarcopenia Map. By including specific diseases, namely liver cirrhosis, and intestinal dysfunction, and considering their effects on nutritional status and blood secretome, we investigated their contribution to the development of sarcopenia. The Sarcopenia Map is publicly available as an open-source, interactive online resource, providing tools that allow users to explore the information on the map and performin silicoperturbation experiments.
Keratose sponges in ancient carbonates – a problem of interpretation
Authors: Neuweiler Fritz , Kershaw Stephen , Boulvain Frédéric , Matysik Michał , Sendino Consuelo , McMenamin Mark , Wood Rachel 
Published: March 2022

ABSTRACTIncreasing current interest in sponge fossils includes numerous reports of diverse vermicular and peloidal structures interpreted as keratose sponges in Neoproterozoic to Mesozoic carbonates and in various open marine to peritidal and restricted settings. Reports of their occurrence are fundamental and far-reaching for understanding microfacies and diagenesis where they occur; and fossil biotic assemblages, as well as wider aspects of origins of animals, sponge evolution/ecology and the systemic recovery from mass extinctions. Keratose sponges: 1) have elaborate spongin skeletons but no spicules, thus lack mineral parts and therefore have poor preservation potential so that determining their presence in rocks requires interpretation; and 2) are presented in publications as interpreted fossil structures almost entirely in two-dimensional (thin section) studies, where structures claimed as sponges comprise diverse layered, network, particulate and amalgamated fabrics involving calcite sparite in a micritic groundmass. There is no verification of sponges in these cases and almost all of them can be otherwise explained; some are certainly not correctly identified. The diversity of structures seen in thin sections may be reinterpreted to include: a) meiofaunal activity; b) layered, possibly microbial (spongiostromate) accretion; c) sedimentary peloidal to clotted micrites; d) fluid escape and capture resulting in birdseye to vuggy porosities; and e) molds of siliceous sponge spicules. Without confirmation of keratose sponges in ancient carbonates, interpretations of their role in ancient carbonate systems, including facies directly after mass extinctions, are unsafe, and alternative explanations for such structures should be considered. This study calls for greater critical appraisal of evidence, to seek confirmation or not, of keratose sponge presence. (259/300 max, for Sedimentology)
Multifactorial remodeling of the cancer immunopeptidome by interferon gamma
Authors: Newey Alice , Yu Lu , Barber Louise J , Choudhary Jyoti S. , Bassani-Sternberg Michal , Gerlinger Marco 
Published: March 2022

AbstractIFNγ alters the immunopeptidome presented on HLA class I (HLA-I), and its activity on cancer cells is known to be important for effective immunotherapy responses. We performed proteomic analyses of untreated and IFNγ-treated colorectal cancer patient-derived organoids (PDOs) and combined this with transcriptomic and HLA-I immunopeptidomics data to dissect mechanisms that lead to remodeling of the immunopeptidome through IFNγ. IFNγ-induced changes in the abundance of source proteins, switching from the constitutive- to the immunoproteasome, and differential upregulation of different HLA alleles explained some, but not all, observed peptide abundance changes. By selecting for peptides which increased or decreased the most in abundance, but originated from proteins with limited abundance changes, we discovered that the amino acid composition of presented peptides also influences whether a peptide is up- or downregulated on HLA-I through IFNγ. The presence of proline within the peptide core was most strongly associated with peptide downregulation. This was validated in an independent dataset. Proline substitution in relevant core positions did not influence the predicted HLA-I binding affinity or stability, indicating that proline effects on peptide processing may be most relevant. Understanding the multiple factors that influence the abundance of peptides presented on HLA-I in the absence or presence of IFNγ is important to identify the best targets for antigen-specific cancer immunotherapies such as vaccines or T-cell receptor engineered therapeutics.
GASOTRANSMITTER MODULATION OF HYPOGLOSSAL MOTONEURON ACTIVITY
Authors: Browe Brigitte , Peng Ying-Jie , Nanduri Jayasri , Prabhakar Nanduri R. , Garcia Alfredo J. 
Published: March 2022

AbstractObstructive sleep apnea (OSA) is characterized by sporadic collapse of the upper airway leading to periodic disruptions in breathing. Upper airway patency governed by genioglossal nerve activity originates from the hypoglossal motor nucleus. Mice with targeted deletion of the gene Hmox2, encoding the carbon monoxide (CO) producing enzyme, heme oxygenase-2 (HO-2), exhibit severe OSA, yet the contribution of central HO-2 dysregulation to the phenomenon is unknown. Using the rhythmic brainstem slice preparation, which contains the preBötzinger complex (preBötC) and the hypoglossal nucleus, we tested the hypothesis that central HO-2 dysregulation weakens hypoglossal motoneuron output. Disrupting HO-2 activity increased transmission failure as determined by the intermittent inability of the preBötC rhythm to trigger output from the hypoglossal nucleus. Failed transmission was associated with a reduced input-output relationship between the preBötC and the motor nucleus. These network phenomena were related to smaller inspiratory drive currents and reduced intrinsic excitability among hypoglossal neurons. In addition to HO-2, hypoglossal neurons also expressed the CO-regulated H2S producing enzyme cystathionine □-lyase (CSE). H2S abundance was higher in hypoglossal neurons of HO-2 null mice than wild-type controls. Disrupting CSE function normalized transmission in HO-2 null mice and an H2S donor mimicked the effects of HO-2 dysregulation. These findings demonstrate a hitherto uncharacterized modulation of hypoglossal activity through the interaction of HO-2 and CSE-derived H2S, and supports the perspective that centrally derived HO-2 activity plays an important role regulating upper airway control.
PPML-Omics: a Privacy-Preserving federated Machine Learning method protects patients’ privacy in omic data
Authors: Zhou Juexiao , Chen Siyuan , Wu Yulian , Li Haoyang , Zhang Bin , Zhou Longxi , Hu Yan , Xiang Zihang , Li Zhongxiao , Chen Ningning , Han Wenkai , Wang Di , Gao Xin 
Published: March 2022

AbstractModern machine learning models towards various tasks with omic data analysis give rise to threats of privacy leakage of patients involved in those datasets. Despite the advances in different privacy technologies, existing methods tend to introduce too much computational cost (e.g. cryptographic methods) or noise (e.g. differential privacy), which hampers either model usefulness or accuracy in protecting privacy in biological data. Here, we proposed a secure and privacy-preserving machine learning method (PPML-Omics) by designing a decentralized version of the differential private federated learning algorithm. We applied PPML-Omics to analyze data from three sequencing technologies, and addressed the privacy concern in three major tasks of omic data, namely cancer classification with bulk RNA-seq, clustering with single-cell RNA-seq, and the integration of spatial gene expression and tumour morphology with spatial transcriptomics, under three representative deep learning models. We also examined privacy breaches in depth through privacy attack experiments and demonstrated that PPML-Omics could protect patients’ privacy. In each of these applications, PPML-Omics was able to outperform methods of comparison under the same level of privacy guarantee, demonstrating the versatility of the method in simultaneously balancing the privacy-preserving capability and utility in practical omic data analysis. Furthermore, we gave the theoretical proof of the privacy-preserving capability of PPML-Omics, suggesting the first mathematically guaranteed method with robust and generalizable empirical performance in protecting patients’ privacy in omic data.
HALO: A software tool for real-time head alignment in the MR scanner
Authors: Zhao Zhiying , Galiana Gigi , Zillo Cristofer , Camarro Terry , Qiu Maolin , Papademetris Xenophon , Hampson Michelle 
Published: March 2022

AbstractMagnetic resonance imaging (MRI) studies in human subjects often require multiple scanning sessions/visits. Changes in a subject’s head position across sessions result in different alignment between brain tissues and the magnetic field which leads to changes in magnetic susceptibility. These changes can have considerable impacts on acquired signals. Therefore, we developed the Head Alignment Optimization (HALO) tool. HALO provides real-time visual feedback of a subject’s current head position relative to the position in a previous session. We verified that HALO enabled subjects to actively align their head positions to the desired position of their initial sessions. Our pilot sample of healthy subjects were able to improve their head alignment significantly using HALO and achieved good alignment with their first session meeting stringent criteria similar to that used for within-run head motion (less than 2mm translation or 2 degrees rotation in any direction from the desired position). Utilization of HALO in longitudinal studies will reduce the noise across sessions related to changes in magnetic susceptibility. HALO has been made publicly available.
EPHierStats: a statistical tool to model the hierarchical relationships in electrophysiological data
Authors: Kolpakova Jenya , Marvel-Zuccola Jonathan D. , Futai Kensuke , Martin Gilles E. , van der Vinne Vincent 
Published: March 2022

AbstractElectrophysiological datasets are typically analyzed under the assumption that repeated measurements of the same unit of analysis (i.e. neuron or animal) can be treated as statistically independent. Recently, this assumption has been questioned and our data confirms and quantifies this skepticism using ex vivo slice recordings of synaptic currents in D1R+ medium spiny neurons in the nucleus accumbens. We therefore present EPHierStats as a statistical framework to analyze electrophysiological datasets with large numbers of measurements (>100) per unit of analysis. This novel analysis framework enables encoding of the full hierarchical relationships between measurements in a mixed-effects general linear model while also analyzing the distribution of values in assessed variables. Our method can easily be adapted to analyze a wide range of repeated-measures electrophysiological experiments. Implementation of the EPHierStats tool will aid the adaption of modern statistical approaches that prevent pseudoreplication and its associated false discovery rate while enabling statistical assessments of the complex relationships inherent to the field of neuroscience.
Cyb5r3-based mechanism and reversal of secondary failure to sulfonylurea
Authors: Watanabe Hitoshi , Du Wen , Son Jinsook , Sui Lina , Asahara Shun-ichiro , Kurland Irwin J , Kuo Taiyi , Kitamoto Takumi , Miyachi Yasutaka , de Cabo Rafael , Accili Domenico 
Published: March 2022

SummarySulfonylureas (SU) are effective and affordable anti-diabetic drugs. But chronic use leads to secondary failure, limiting their utilization. The mechanism of secondary failure is unknown. Here we identify Cyb5r3 downregulation as a mechanism of SU failure and successfully reverse it. Chronic exposure to SU impairs Cyb5r3 levels and reduces islet glucose utilization with a metabolomics signature characterized by low acetyl-CoA and amino acid levels. Cyb5r3 engages in a glucose-dependent interaction that stabilizes glucokinase (Gck) to maintain glucose utilization. Accordingly, activating Gck mutations in patients with hyperinsulinemia reduce Cyb5r3 binding, whereas inactivating MODY mutations increase it, providing evidence for a role of Cyb5r3 in determining flux through Gck. The Cyb5r3 activator tetrahydroindenoindole (THII) rescues secondary failure to SU in an animal model of chronic SU treatment and restores insulin secretion from ex vivo islets. We conclude that Cyb5r3 loss-of-function is a key factor in the secondary failure to SU and a potential target for its prevention, which may lead to a rehabilitation of SU use in diabetes.
L-GIREMI uncovers RNA editing sites in long-read RNA-seq
Authors: Liu Zhiheng , Quinones-Valdez Giovanni , Fu Ting , Choudhury Mudra , Reese Fairlie , Mortazavi Ali , Xiao Xinshu 
Published: March 2022

AbstractUsing third-generation sequencers, long-read RNA-seq is increasingly applied in transcriptomic studies given its major advantage in characterizing full-length transcripts. A number of methods have been developed to analyze this new type of data for transcript isoforms and their abundance. Another application, which is significantly under-explored, is to identify and analyze single nucleotide variants (SNVs) in the RNA. Identification of SNVs, such as genetic mutations or RNA editing sites, is fundamental to many biomedical questions. In long-read RNA-seq, SNV analysis presents significant challenges, due to the well-known relatively high error rates of the third-generation sequencers. Here, we present the first study to detect and analyze RNA editing sites in long-read RNA-seq. Our new method, L-GIREMI, effectively handles sequencing errors and biases in the reads, and uses a model-based approach to score RNA editing sites. Applied to PacBio long-read RNA-seq data, L-GIREMI affords a high accuracy in RNA editing identification. In addition, the unique advantage of long reads allowed us to uncover novel insights about RNA editing occurrences in single molecules and double-stranded RNA (dsRNA) structures. L-GIREMI provides a valuable means to study RNA nucleotide variants in long-read RNA-seq.