bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of inflammatory subgroups of schizophrenia and bipolar disorder patients with HERV-W ENV antigenemia by unsupervised cluster analysis
Authors: Tamouza Ryad , Meyer Urs , Foiselle Marianne , Richard Jean-Romain , Wu Ching-Lien , Boukouaci Wahid , Le Corvoisier Philippe , Barrau Caroline , Lucas Alexandre , Perron Hervé , Leboyer Marion 
Published: July 2021

AbstractHuman endogenous retroviruses (HERVs) are remnants of infections that took place several million years ago and represent around 8% of the human genome. Despite evidence implicating increased expression of HERV type W envelope (HERV-W ENV) in schizophrenia and bipolar disorder, it remains unknown whether such expression is associated with distinct clinical or biological characteristics and symptoms. Accordingly, we performed unsupervised two-step clustering of a multivariate data set that included HERV-W ENV protein antigenemia, serum cytokine levels, childhood trauma scores, and clinical data of cohorts of patients with schizophrenia (n = 29), bipolar disorder (n = 43) and healthy controls (n = 32). We found that subsets of patients with schizophrenia (~41%) and bipolar disorder (~28%) show positive antigenemia for HERV-W ENV protein, whereas the large majority (96%) of controls was found to be negative for ENV protein. Unsupervised cluster analysis identified the presence of two main clusters of patients, which were best predicted by the presence or absence of HERV-W ENV protein. HERV-W expression was associated with increased serum levels of inflammatory cytokines and higher childhood maltreatment scores. Furthermore, patients with schizophrenia who were positive for HERV-W ENV protein showed more manic symptoms and higher daily chlorpromazine (CPZ) equivalents, whereas HERV-W ENV positive patients with bipolar disorder were found to have an earlier disease onset than those who were negative for HERV-W ENV protein. Taken together, our study suggest that HERV-W ENV protein antigenemia and cytokines can be used to stratify patients with major mood and psychotic disorders into subgroups with differing inflammatory and clinical profiles.
Comparable level of aggression between patients with behavioural addiction and healthy subjects
Authors: Asaoka Yui , Won Moojun , Morita Tomonari , Ishikawa Emi , Goto Yukiori 
Published: July 2021

AbstractHeightened aggression is identified in several psychiatric disorders, including addiction. In this preliminary study with a relatively small number of samples, aggression in subjects diagnosed with behavioural addiction (BA) was implicitly assessed using the point subtraction aggression paradigm (PSAP) test along with measurements of oxy- and deoxyhaemoglobin dynamics in the prefrontal cortex (PFC) during the test using functional near-infrared spectroscopy. Aggression in BA patients was no higher than that of healthy control (CT) subjects in the PSAP test. Although no apparent increase or decrease in haemoglobin concentrations was observed in the PFC of either BA patients or CT subjects, abnormal correlations within the PFC network were present in BA patients. Consistent with comparable aggression between the groups, blood concentrations of the sex hormone testosterone, which has been shown to be associated with aggressiveness, was even lower in BA patients than in CT subjects. In contrast, when a set of questionnaire surveys for the assessment of aggression were administered, BA patients rated themselves as more aggressive than non-BA subjects. Collectively, these results suggest that aggression may not be heightened in BA, but BA patients may overestimate their aggressiveness, raising concerns about the use of questionnaire surveys for assessments of affective traits such as aggression in behavioural addiction.
Overexpression of Lrp5 enhanced the anti-breast cancer effects of osteocytes in bone
Authors: Liu Shengzhi , Wu Di , Sun Xun , Fan Yao , Zha Rongrong , Jalali Aydin , Feng Yan , Li Kexin , Sano Tomohiko , Vike Nicole , Li Fangjia , Rispoli Joseph , Sudo Akihiro , Liu Jing , Robling Alexander , Nakshatri Harikrishna , Li Bai-Yan , Yokota Hiroki 
Published: July 2021

AbstractOsteocytes are the most abundant cells in bone, which is a frequent site of breast cancer metastasis. Here, we focused on Wnt signaling and evaluated tumor-osteocyte interactions. In animal experiments, mammary tumor cells were inoculated into the mammary fat pad and tibia. The role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse model. The results revealed that administration of osteocytes or their conditioned medium (CM) inhibited tumor progression and osteolysis. Osteocytes overexpressing Lrp5 or β-catenin displayed strikingly elevated tumor-suppressive activity, accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as p53. The antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating compound. Notably, silencing Lrp5 in tumors inhibited tumor progression, while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor progression. Osteocytes exhibited elevated Lrp5 expression in response to tumor cells, implying that osteocytes protect bone through canonical Wnt signaling. Thus, our results suggest that the Lrp5/β-catenin axis activates tumor-promoting signaling in tumor cells but tumor-suppressive signaling in osteocytes. We envision that osteocytes with Wnt activation potentially offer a novel cell-based therapy for breast cancer and osteolytic bone metastasis.
An MDM2 inhibitor achieves synergistic cytotoxic effects with adenoviruses lacking E1B55kDa gene on mesothelioma with the wild-type p53 through augmenting NFI expression
Authors: Nguyen Thao Thi Thanh , Shingyoji Masato , Hanazono Michiko , Zhong Boya , Morinaga Takao , Tada Yuji , Shimada Hideaki , Hiroshima Kenzo , Tagawa Masatoshi 
Published: July 2021

AbstractA majority of mesothelioma specimens were defective of p14 and p16 expression due to deletion of the INK4A/ARF region, and the p53 pathway was consequently inactivated by elevated MDM2 functions which facilitated p53 degradaton. We investigated a role of p53 elevation by MDM2 inhibitors, nutlin-3a and RG7112, in cytotoxicity of replication-competent adenoviruses (Ad) lacking the p53-binding E1B55kDa gene (Ad-delE1B). We found that a growth inhibition by p53-activating Ad-delE1B was irrelevant to p53 expression in the infected cells, but combination of Ad-delE1B and the MDM2 inhibitor produced synergistic inhibitory effects on mesothelioma with the wild-type but not mutated p53 genotype. The combination augmented p53 phosphorylation, activated apoptotic but not autophagic pathway, and enhanced DNA damage signals through ATM-Chk2 phosphorylation. The MDM2 inhibitors facilitated production of the Ad progenies through augmented expression of nuclear factor I (NFI), one of the transcriptional factors involved in Ad replications. Knocking down of p53 with siRNA did not increase the progeny production or the NFI expression. We also demonstrated anti-tumor effects by the combination of Ad-delE1B and the MDM2 inhibitors in an orthotopic animal model. These data collectively indicated that upregulation of wild-type p53 expression contributed to cytotoxicity by E1B55kDa-defective replicative Ad through NFI induction and suggested that replication-competent Ad together with augmented p53 levels was a therapeutic strategy for p53 wild-type mesothelioma.
Determination of the dynamic cellular transcriptional profiles during kidney development from birth to maturity in rats by single-cell RNA sequencing
Authors: Ding Fangrui , Tian Xiuying , Mo Jiali , Wang Botao , Zheng Jun 
Published: July 2021

AbstractRecent single-cell RNA sequencing (scRNA-seq) analyses have offered much insight into the gene expression profiles in early-stage kidney development. However, comprehensive gene expression profiles from mid- and late-stage kidney development are lacking. In the present study, by using the scRNA-seq technique, we analyzed 54,704 rat kidney cells from just after birth to adulthood (six time points: postnatal days 0, 2, 5, 10, 20, and 56) including the mid and late stages of kidney development. Twenty-five original clusters and 13 different cell types were identified during these stages. Gene expression in these 13 cell types was mapped, and single cell atlas of the rat kidney from birth to maturity (http://youngbearlab.com) was built to enable users to search for a gene of interest and to evaluate its expression in different cells. The variation trend of six major types of kidney cells—intercalated cells of the collecting duct (CD-ICs), principal cells of the collecting duct (CD-PCs), cells of the distal convoluted tubules (DCTs), cells of the loop of Henle (LOH), podocytes (PDs), and cells of the proximal tubules (PTs)—during six postnatal time points was demonstrated. The trajectory of rat kidney development and the order of induction of the six major types of kidney cells from just after birth to maturity were determined. In addition, features of the dynamically changing genes as well as transcription factors during postnatal rat kidney development were identified. The present study provides a resource for achieving a deep understanding of the molecular basis of and regulatory events in the mid and late stages of kidney development.
Endothelial-specific insulin receptor substrate-1 overexpression worsens neonatal hypoxic-ischemic brain injury via mTOR-mediated tight junction disassembly
Authors: Tu Yi-Fang , Jiang Si-Tse , Chiang Chi-Wu , Chen Li-Ching , Huang Chao-Ching 
Published: July 2021

AbstractHypoxic-ischemic (HI) encephalopathy is the major cause of mortality and disability in newborns. The neurovascular unit is a major target of acute and chronic brain injury, and therapies that protect simultaneously both neurons and vascular endothelial cells from neonatal HI injury are in demand. Insulin receptors and its key downstream molecule-insulin receptor substrate −1 (IRS-1) are potential neuroprotective targets and expressed both in neuron and endothelial cells. To investigate whether IRS-1 can act similarly in neurons and vascular endothelial cells in protecting neurovascular units and brain form HI injury, we found that neuron-specific IRS-1 transgenic rats showed reduced neurovascular injury and infarct volumes, whereas endothelial-specific IRS-1 transgenic rats showed increased blood-brain barrier (BBB) disruption and exaggerated neurovascular injury after neonatal HI brain injury. Endothelial-specific IRS-1 overexpression increased vascular permeability and disassembled the tight junction protein (zonula occludens-1) complex. Inhibition of mammalian target of rapamycin (mTOR) by rapamycin preserved tight junction proteins and attenuated BBB leakage and neuronal apoptosis after HI in the endothelial-specific IRS-1 transgenic pups. Together, our findings suggested that neuronal and endothelial IRS-1 had opposite effects on the neurovascular integrity and damage after neonatal HI brain injury and that endothelial IRS-1 worsens neurovascular integrity after HI via mTOR-mediated tight junction protein disassembly.
Implication of ferroptosis in aging
Authors: Mazhar Maryam , Din Ahmad Ud , Ali Hamid , Yang Guoqiang , Ren Wei , Wang Li , Fan Xiaohui , Yang Sijin 
Published: July 2021

AbstractLife is indeed continuously going through the irreversible and inevitable process of aging. The rate of aging process depends on various factors and varies individually. These factors include various environmental stimuli including exposure to toxic chemicals, psychological stress whereas suffering with various illnesses specially the chronic diseases serve as endogenous triggers. The basic underlying mechanism for all kinds of stresses is now known to be manifested as production of excessive ROS, exhaustion of ROS neutralizing antioxidant enzymes and proteins leading to imbalance in oxidation and antioxidant processes with subsequent oxidative stress induced inflammation affecting the cells, tissues, organs and the whole body. All these factors lead to conventional cell death either through necrosis, apoptosis, or autophagy. Currently, a newly identified mechanism of iron dependent regulated cell death called ferroptosis, is of special interest for its implication in pathogenesis of various diseases such as cardiovascular disease, neurological disorders, cancers, and various other age-related disorders (ARD). In ferroptosis, the cell death occur neither by conventional apoptosis, necrosis nor by autophagy, rather dysregulated iron in the cell mediates excessive lipid peroxidation of accumulated lethal lipids. It is not surprising to assume its role in aging as previous research have identified some solid cues on the subject. In this review, we will highlight the factual evidences to support the possible role and implication of ferroptosis in aging in order to declare the need to identify and explore the interventions to prevent excessive ferroptosis leading to accelerated aging and associated liabilities of aging.
Methyltransferase-like protein 7A (METTL7A) promotes cell survival and osteogenic differentiation under metabolic stress
Authors: Lee Eugene , Kim Ju-young , Kim Tae-Kyung , Park Seo-Young , Im Gun-Il 
Published: July 2021

AbstractWhile bone has an inherent capacity to heal itself, it is very difficult to reconstitute large bone defects. Regenerative medicine, including stem cell implantation, has been studied as a novel solution to treat these conditions. However, when the local vascularity is impaired, even the transplanted cells undergo rapid necrosis before differentiating into osteoblasts and regenerating bone. Thus, to increase the effectiveness of stem cell transplantation, it is quintessential to improve the viability of the implanted stem cells. In this study, given that the regulation of glucose may hold the key to stem cell survival and osteogenic differentiation, we investigated the molecules that can replace the effect of glucose under ischemic microenvironment of stem cell transplantation in large bone defects. By analyzing differentially expressed genes under glucose-supplemented and glucose-free conditions, we explored markers such as methyltransferase-like protein 7A (METTL7A) that are potentially related to cell survival and osteogenic differentiation. Overexpression of METTL7A gene enhanced the osteogenic differentiation and viability of human bone marrow stem cells (hBMSCs) in glucose-free conditions. When the in vivo effectiveness of METTL7A-transfected cells in bone regeneration was explored in a rat model of critical-size segmental long-bone defect, METTL7A-transfected hBMSCs showed significantly better regenerative potential than the control vector-transfected hBMSCs. DNA methylation profiles showed a large difference in methylation status of genes related to osteogenesis and cell survival between hBMSCs cultured in glucose-supplemented condition and those cultured in glucose-free condition. Interestingly, METTL7A overexpression altered the methylation status of related genes to favor osteogenic differentiation and cell survival. In conclusion, it is suggested that a novel factor METTL7A enhances osteogenic differentiation and viability of hBMSCs by regulating the methylation status of genes related to osteogenesis or survival.
A chromosome-scale genome sequence of pitaya (Hylocereus undatus) provides novel insights into the genome evolution and regulation of betalain biosynthesis
Authors: Chen Jian-ye , Xie Fang-fang , Cui Yan-ze , Chen Can-bin , Lu Wang-jin , Hu Xiao-di , Hua Qing-zhu , Zhao Jing , Wu Zhi-jiang , Gao Dan , Zhang Zhi-ke , Jiang Wen-kai , Sun Qing-ming , Hu Gui-bing , Qin Yong-hua 
Published: July 2021

AbstractPitaya (Hylocereus) is the most economically important fleshy-fruited tree of the Cactaceae family that is grown worldwide, and it has attracted significant attention because of its betalain-abundant fruits. Nonetheless, the lack of a pitaya reference genome significantly hinders studies focused on its evolution, as well as the potential for genetic improvement of this crop. Herein, we employed various sequencing approaches, namely, PacBio-SMRT, Illumina HiSeq paired-end, 10× Genomics, and Hi-C (high-throughput chromosome conformation capture) to provide a chromosome-level genomic assembly of ‘GHB’ pitaya (H. undatus, 2n = 2x = 22 chromosomes). The size of the assembled pitaya genome was 1.41 Gb, with a scaffold N50 of ~127.15 Mb. In total, 27,753 protein-coding genes and 896.31 Mb of repetitive sequences in the H. undatus genome were annotated. Pitaya has undergone a WGT (whole-genome triplication), and a recent WGD (whole-genome duplication) occurred after the gamma event, which is common to the other species in Cactaceae. A total of 29,328 intact LTR-RTs (~696.45 Mb) were obtained in H. undatus, of which two significantly expanded lineages, Ty1/copia and Ty3/gypsy, were the main drivers of the expanded genome. A high-density genetic map of F1 hybrid populations of ‘GHB’ × ‘Dahong’ pitayas (H. monacanthus) and their parents were constructed, and a total of 20,872 bin markers were identified (56,380 SNPs) for 11 linkage groups. More importantly, through transcriptomic and WGCNA (weighted gene coexpression network analysis), a global view of the gene regulatory network, including structural genes and the transcription factors involved in pitaya fruit betalain biosynthesis, was presented. Our data present a valuable resource for facilitating molecular breeding programs of pitaya and shed novel light on its genomic evolution, as well as the modulation of betalain biosynthesis in edible fruits.
Anthropogenic influence on extreme precipitation over global land areas seen in multiple observational datasets
Authors: Madakumbura Gavin D. , Thackeray Chad W. , Norris Jesse , Goldenson Naomi , Hall Alex 
Published: July 2021

AbstractThe intensification of extreme precipitation under anthropogenic forcing is robustly projected by global climate models, but highly challenging to detect in the observational record. Large internal variability distorts this anthropogenic signal. Models produce diverse magnitudes of precipitation response to anthropogenic forcing, largely due to differing schemes for parameterizing subgrid-scale processes. Meanwhile, multiple global observational datasets of daily precipitation exist, developed using varying techniques and inhomogeneously sampled data in space and time. Previous attempts to detect human influence on extreme precipitation have not incorporated model uncertainty, and have been limited to specific regions and observational datasets. Using machine learning methods that can account for these uncertainties and capable of identifying the time evolution of the spatial patterns, we find a physically interpretable anthropogenic signal that is detectable in all global observational datasets. Machine learning efficiently generates multiple lines of evidence supporting detection of an anthropogenic signal in global extreme precipitation.
Reward biases spontaneous neural reactivation during sleep
Authors: Sterpenich Virginie , van Schie Mojca K. M. , Catsiyannis Maximilien , Ramyead Avinash , Perrig Stephen , Yang Hee-Deok , Van De Ville Dimitri , Schwartz Sophie 
Published: July 2021

AbstractSleep favors the reactivation and consolidation of newly acquired memories. Yet, how our brain selects the noteworthy information to be reprocessed during sleep remains largely unknown. From an evolutionary perspective, individuals must retain information that promotes survival, such as avoiding dangers, finding food, or obtaining praise or money. Here, we test whether neural representations of rewarded (compared to non-rewarded) events have priority for reactivation during sleep. Using functional MRI and a brain decoding approach, we show that patterns of brain activity observed during waking behavior spontaneously reemerge during slow-wave sleep. Critically, we report a privileged reactivation of neural patterns previously associated with a rewarded task (i.e., winning at a complex game). Moreover, during sleep, activity in task-related brain regions correlates with better subsequent memory performance. Our study uncovers a neural mechanism whereby rewarded life experiences are preferentially replayed and consolidated while we sleep.
Large-scale characterization of sex pheromone communication systems in Drosophila
Authors: Khallaf Mohammed A. , Cui Rongfeng , Weißflog Jerrit , Erdogmus Maide , Svatoš Aleš , Dweck Hany K. M. , Valenzano Dario Riccardo , Hansson Bill S. , Knaden Markus 
Published: July 2021

AbstractInsects use sex pheromones as a reproductive isolating mechanism to attract conspecifics and repel heterospecifics. Despite the profound knowledge of sex pheromones, little is known about the coevolutionary mechanisms and constraints on their production and detection. Using whole-genome sequences to infer the kinship among 99 drosophilids, we investigate how phylogenetic and chemical traits have interacted at a wide evolutionary timescale. Through a series of chemical syntheses and electrophysiological recordings, we identify 52 sex-specific compounds, many of which are detected via olfaction. Behavioral analyses reveal that many of the 43 male-specific compounds are transferred to the female during copulation and mediate female receptivity and/or male courtship inhibition. Measurement of phylogenetic signals demonstrates that sex pheromones and their cognate olfactory channels evolve rapidly and independently over evolutionary time to guarantee efficient intra- and inter-specific communication systems. Our results show how sexual isolation barriers between species can be reinforced by species-specific olfactory signals.
Piezoacoustics for precision control of electrons floating on helium
Authors: Byeon H. , Nasyedkin K. , Lane J. R. , Beysengulov N. R. , Zhang L. , Loloee R. , Pollanen J. 
Published: July 2021

AbstractPiezoelectric surface acoustic waves (SAWs) are powerful for investigating and controlling elementary and collective excitations in condensed matter. In semiconductor two-dimensional electron systems SAWs have been used to reveal the spatial and temporal structure of electronic states, produce quantized charge pumping, and transfer quantum information. In contrast to semiconductors, electrons trapped above the surface of superfluid helium form an ultra-high mobility, two-dimensional electron system home to strongly-interacting Coulomb liquid and solid states, which exhibit non-trivial spatial structure and temporal dynamics prime for SAW-based experiments. Here we report on the coupling of electrons on helium to an evanescent piezoelectric SAW. We demonstrate precision acoustoelectric transport of as little as ~0.01% of the electrons, opening the door to future quantized charge pumping experiments. We also show SAWs are a route to investigating the high-frequency dynamical response, and relaxational processes, of collective excitations of the electronic liquid and solid phases of electrons on helium.