bluuebunny/crossref_metadata_2025_split huggingface dataset:
TOB is an effector of the hippocampus-mediated acute stress response
Authors: Youssef Mohieldin M. M. , Hamada Hiro Taiyo , Lai Esther Suk King , Kiyama Yuji , El-Tabbal Mohamed , Kiyonari Hiroshi , Nakano Kohei , Kuhn Bernd , Yamamoto Tadashi 
Published: July 2022

AbstractStress affects behavior and involves critical dynamic changes at multiple levels ranging from molecular pathways to neural circuits and behavior. Abnormalities at any of these levels lead to decreased stress resilience and pathological behavior. However, temporal modulation of molecular pathways underlying stress response remains poorly understood. Transducer of ErbB2.1, known as TOB, is involved in different physiological functions, including cellular stress and immediate response to stimulation. In this study, we investigated the role of TOB in psychological stress machinery at molecular, neural circuit, and behavioral levels. Interestingly, TOB protein levels increased after mice were exposed to acute stress. At the neural circuit level, functional magnetic resonance imaging (fMRI) suggested that intra-hippocampal and hippocampal-prefrontal connectivity were dysregulated in Tob knockout (Tob-KO) mice. Electrophysiological recordings in hippocampal slices showed increased postsynaptic AMPAR-mediated neurotransmission, accompanied by decreased GABA neurotransmission and subsequently altered Excitatory/Inhibitory balance after Tob deletion. At the behavioral level, Tob-KO mice show abnormal, hippocampus-dependent, contextual fear conditioning and extinction, and depression-like behaviors. On the other hand, increased anxiety observed in Tob-KO mice is hippocampus-independent. At the molecular level, we observed changes in factors involved in stress response like decreased stress-induced LCN2 expression and ERK phosphorylation, as well as increased MKP-1 expression. This study introduces TOB as an important modulator in the hippocampal stress signaling machinery. In summary, we reveal a molecular pathway and neural circuit mechanism by which Tob deletion contributes to expression of pathological stress-related behavior.
Lactate promotes metastasis of normoxic colorectal cancer stem cells through PGC-1α-mediated oxidative phosphorylation
Authors: Liu Shuang , Zhao Hui , Hu Yibing , Yan Chang , Mi Yulong , Li Xiaolan , Tao Deding , Qin Jichao 
Published: July 2022

AbstractUneven oxygen supply in solid tumors leads to hypoxic and normoxic regions. Hypoxic cells exhibit increased secretion of lactate, which creates an acidic tumor microenvironment (TME). This acidic TME is positively associated with tumor metastasis. Despite the increased metastatic capacity of hypoxic cells, they are located relatively further away from the blood vessels and have limited access to the circulatory system. Studies have shown that cancer stem cells (CSCs) are enriched for tumor metastasis-initiating cells and generally undergo aerobic respiration, which could be enhanced by lactate. We therefore hypothesized that TME-derived lactate may promote the metastasis of normoxic CSCs. In the present study, the abundance of hypoxic and normoxic CSCs was analyzed in primary CRC tumors. It was found that the proportion of normoxic CSCs was positively associated with tumor stage. Using two human CRC cell lines, LoVo and SW480, and a patient-derived xenograft (XhCRC), it was found that treatment with lactate promoted normoxic CSC metastasis. Metabolism analysis indicated that, upon treatment with lactate, oxidative phosphorylation (OXPHOS) activity in normoxic CSCs was enhanced, whereas hypoxic CSCs were rarely altered. At the molecular level, the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of lactate oxidation, was found to be elevated in normoxic CSCs. Furthermore, PGC-1α knockdown markedly reduced the metastatic potential of normoxic CSCs. Notably, both the PGC-1α-mediated OXPHOS activity and metastatic potential were impaired when hypoxia-inducible factor-1α (HIF-1α) was activated in normoxic CSCs. Together, these findings provide a therapeutic strategy against tumor metastasis through the targeting of PGC-1α and, thus, the suppression of lactate-feeding OXPHOS in normoxic CSCs may improve the therapeutic benefit of patients with cancer, particularly CRC.
Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression
Authors: Larivière Sara , Royer Jessica , Rodríguez-Cruces Raúl , Paquola Casey , Caligiuri Maria Eugenia , Gambardella Antonio , Concha Luis , Keller Simon S. , Cendes Fernando , Yasuda Clarissa L. , Bonilha Leonardo , Gleichgerrcht Ezequiel , Focke Niels K. , Domin Martin , von Podewills Felix , Langner Soenke , Rummel Christian , Wiest Roland , Martin Pascal , Kotikalapudi Raviteja , O’Brien Terence J. , Sinclair Benjamin , Vivash Lucy , Desmond Patricia M. , Lui Elaine , Vaudano Anna Elisabetta , Meletti Stefano , Tondelli Manuela , Alhusaini Saud , Doherty Colin P. , Cavalleri Gianpiero L. , Delanty Norman , Kälviäinen Reetta , Jackson Graeme D. , Kowalczyk Magdalena , Mascalchi Mario , Semmelroch Mira , Thomas Rhys H. , Soltanian-Zadeh Hamid , Davoodi-Bojd Esmaeil , Zhang Junsong , Winston Gavin P. , Griffin Aoife , Singh Aditi , Tiwari Vijay K. , Kreilkamp Barbara A. K. , Lenge Matteo , Guerrini Renzo , Hamandi Khalid , Foley Sonya , Rüber Theodor , Weber Bernd , Depondt Chantal , Absil Julie , Carr Sarah J. A. , Abela Eugenio , Richardson Mark P. , Devinsky Orrin , Severino Mariasavina , Striano Pasquale , Tortora Domenico , Kaestner Erik , Hatton Sean N. , Vos Sjoerd B. , Caciagli Lorenzo , Duncan John S. , Whelan Christopher D. , Thompson Paul M. , Sisodiya Sanjay M. , Bernasconi Andrea , Labate Angelo , McDonald Carrie R. , Bernasconi Neda , Bernhardt Boris C. 
Published: July 2022

AbstractEpilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes.
Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity
Authors: Deaton Aimee M. , Dubey Aditi , Ward Lucas D. , Dornbos Peter , Flannick Jason ,   AMP-T2D-GENES Consortium, Yee Elaine , Ticau Simina , Noetzli Leila , Parker Margaret M. , Hoffing Rachel A. , Willis Carissa , Plekan Mollie E. , Holleman Aaron M. , Hinkle Gregory , Fitzgerald Kevin , Vaishnaw Akshay K. , Nioi Paul 
Published: July 2022

AbstractIdentifying genetic variants associated with lower waist-to-hip ratio can reveal new therapeutic targets for abdominal obesity. We use exome sequences from 362,679 individuals to identify genes associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI), a surrogate for abdominal fat that is causally linked to type 2 diabetes and coronary heart disease. Predicted loss of function (pLOF) variants inINHBEassociate with lower WHRadjBMI and this association replicates in data from AMP-T2D-GENES.INHBEencodes a secreted protein, the hepatokine activin E. In vitro characterization of the most commonINHBEpLOF variant in our study, indicates an in-frame deletion resulting in a 90% reduction in secreted protein levels. We detect associations with lower WHRadjBMI for variants inACVR1C, encoding an activin receptor, further highlighting the involvement of activins in regulating fat distribution. These findings highlight activin E as a potential therapeutic target for abdominal obesity, a phenotype linked to cardiometabolic disease.
Body size, shape and ecology in tetrapods
Authors: Maher Alice E. , Burin Gustavo , Cox Philip G. , Maddox Thomas W. , Maidment Susannah C. R. , Cooper Natalie , Schachner Emma R. , Bates Karl T. 
Published: July 2022

AbstractBody size and shape play fundamental roles in organismal function and it is expected that animals may possess body proportions that are well-suited to their ecological niche. Tetrapods exhibit a diverse array of body shapes, but to date this diversity in body proportions and its relationship to ecology have not been systematically quantified. Using whole-body skeletal models of 410 extinct and extant tetrapods, we show that allometric relationships vary across individual body segments thereby yielding changes in overall body shape as size increases. However, we also find statistical support for quadratic relationships indicative of differential scaling in small-medium versus large animals. Comparisons of locomotor and dietary groups highlight key differences in body proportions that may mechanistically underlie occupation of major ecological niches. Our results emphasise the pivotal role of body proportions in the broad-scale ecological diversity of tetrapods.
Development of quasi-solid-state anode-free high-energy lithium sulfide-based batteries
Authors: Liu Yuzhao , Meng Xiangyu , Wang Zhiyu , Qiu Jieshan 
Published: July 2022

AbstractAnode-free lithium batteries without lithium metal excess are a practical option to maximize the energy content beyond the conventional design of Li-ion and Li metal batteries. However, their performance and reliability are still limited by using low-capacity oxygen-releasing intercalation cathodes and flammable liquid electrolytes. Herein, we propose quasi-solid-state anode-free batteries containing lithium sulfide-based cathodes and non-flammable polymeric gel electrolytes. Such batteries exhibit an energy density of 1323 Wh L−1 at the pouch cell level. Moreover, the lithium sulfide-based anode-free cell chemistry endows intrinsic safety thanks to a lack of uncontrolled exothermic reactions of reactive oxygen and excess Li inventory. Furthermore, the non-flammable gel electrolyte, developed from MXene-doped fluorinated polymer, inhibits polysulfide shuttling, hinders Li dendrite formation and further secures cell safety. Finally, we demonstrate the improved cell safety against mechanical, electrical and thermal abuses.
Ammonia for post-healing of formamidinium-based Perovskite films
Authors: Li Zhipeng , Wang Xiao , Wang Zaiwei , Shao Zhipeng , Hao Lianzheng , Rao Yi , Chen Chen , Liu Dachang , Zhao Qiangqiang , Sun Xiuhong , Gao Caiyun , Zhang Bingqian , Wang Xianzhao , Wang Li , Cui Guanglei , Pang Shuping 
Published: July 2022

AbstractSolvents employed for perovskite film fabrication not only play important roles in dissolving the precursors but also participate in crystallization process. High boiling point aprotic solvents with O-donor ligands have been extensively studied, but the formation of a highly uniform halide perovskite film still requires the participation of additives or an additional step to accelerate the nucleation rate. The volatile aliphatic methylamine with both coordinating ligands and hydrogen protons as solvent or post-healing gas facilitates the process of methylamine-based perovskite films with high crystallinity, few defects, and easy large-scale fabrication as well. However, the attempt in formamidinium-containing perovskites is challenged heretofore. Here, we reveal that the degradation of formamidinium-containing perovskites in aliphatic amines environment results from the transimination reaction of formamidinium cation and aliphatic amines along with the formation of ammonia. Based on this mechanism, ammonia is selected as a post-healing gas for a highly uniform, compact formamidinium-based perovskite films. In particular, low temperature is proved to be crucial to enable formamidinium-based perovskite materials to absorb enough ammonia molecules and form a liquid intermediate state which is the key to eliminating voids in raw films. As a result, the champion perovskite solar cell based on ammonia post-healing achieves a power conversion efficiency of 23.21% with excellent reproducibility. Especially the module power conversion efficiency with 14 cm2 active area is over 20%. This ammonia post-healing treatment potentially makes it easier to upscale fabrication of highly efficient formamidinium-based devices.
Metagenomic analysis reveals associations between salivary microbiota and body composition in early childhood
Authors: Coker Modupe O. , Lebeaux Rebecca M. , Hoen Anne G. , Moroishi Yuka , Gilbert-Diamond Diane , Dade Erika F. , Palys Thomas J. , Madan Juliette C. , Karagas Margaret R. 
Published: July 2022

AbstractSeveral studies have shown that body mass index is strongly associated with differences in gut microbiota, but the relationship between body weight and oral microbiota is less clear especially in young children. We aimed to evaluate if there is an association between child growth and the saliva microbiome. We hypothesized that associations between growth and the saliva microbiome would be moderate, similarly to the association between growth and the gut microbiome. For 236 toddlers participating in the New Hampshire Birth Cohort Study, we characterized the association between multiple longitudinal anthropometric measures of body height, body weight and body mass. Body Mass Index (BMI) z-scores were calculated, and dual-energy x-ray absorptiometry (DXA) was used to estimate body composition. Shotgun metagenomic sequencing of saliva samples was performed to taxonomically and functionally profile the oral microbiome. We found that within-sample diversity was inversely related to body mass measurements while community composition was not associated. Although the magnitude of associations were small, some taxa were consistently associated with growth and modified by sex. Certain taxa were associated with decreased weight or growth (including Actinomyces odontolyticus and Prevotella melaninogenica) or increased growth (such as Streptococcus mitis and Corynebacterium matruchotii) across anthropometric measures. Further exploration of the functional significance of this relationship will enhance our understanding of the intersection between weight gain, microbiota, and energy metabolism and the potential role of these relationships on the onset of obesity-associated diseases in later life.
Genetic variation as a long-distance modulator of RAD21 expression in humans
Authors: Schierding William , Horsfield Julia A. , O’Sullivan Justin 
Published: July 2022

AbstractSomatic mutations and changes in expression of RAD21 are common in many types of cancer. Moreover, sub-optimal levels of RAD21 expression in early development can result in cohesinopathies. Altered RAD21 levels can result directly from mutations in the RAD21 gene. However, whether DNA variants outside of the RAD21 gene could control its expression and thereby contribute to cancer and developmental disease is unknown. In this study, we searched for genomic variants that modify RAD21expression to determine their potential to contribute to development or cancer by RAD21 dysregulation. We searched 42,953,834 genomic variants for a spatial-eQTL association with the transcription of RAD21. We identified 123 significant associations (FDR < 0.05), which are local (cis) or long-distance (trans) regulators of RAD21 expression. The 123 variants co-regulate a further seven genes (AARD, AKAP11, GRID1, KCNIP4, RCN1, TRIOBP, and USP32), enriched for having Sp2 transcription factor binding sites in their promoter regions. The Sp2 transcription factor and six of the seven genes had previously been associated with cancer onset, progression, and metastasis. Our results suggest that genome-wide variation in non-coding regions impacts on RAD21 transcript levels in addition to other genes, which then could impact on oncogenesis and the process of ubiquitination. This identification of distant co-regulation of oncogenes represents a strategy for discovery of novel genetic regions influencing cancer onset and a potential for diagnostics.
A ricin-based peptide BRIP from Hordeum vulgare inhibits Mpro of SARS-CoV-2
Authors: Kashyap Prakriti , Bhardwaj Vijay Kumar , Chauhan Mahima , Chauhan Varun , Kumar Asheesh , Purohit Rituraj , Kumar Arun , Kumar Sanjay 
Published: July 2022

AbstractCOVID-19 pandemic caused by SARS-CoV-2 led to the research aiming to find the inhibitors of this virus. Towards this world problem, an attempt was made to identify SARS-CoV-2 main protease (Mpro) inhibitory peptides from ricin domains. The ricin-based peptide from barley (BRIP) was able to inhibit Mpro in vitro with an IC50 of 0.52 nM. Its low and no cytotoxicity upto 50 µM suggested its therapeutic potential against SARS-CoV-2. The most favorable binding site on Mpro was identified by molecular docking and steered molecular dynamics (MD) simulations. The Mpro-BRIP interactions were further investigated by evaluating the trajectories for microsecond timescale MD simulations. The structural parameters of Mpro-BRIP complex were stable, and the presence of oppositely charged surfaces on the binding interface of BRIP and Mpro complex further contributed to the overall stability of the protein-peptide complex. Among the components of thermodynamic binding free energy, Van der Waals and electrostatic contributions were most favorable for complex formation. Our findings provide novel insight into the area of inhibitor development against COVID-19.
The mechanical characterization of the legs, fangs, and prosoma in the spider Harpactira curvipes (Pocock 1897)
Authors: Residori Sara , Greco Gabriele , Pugno Nicola M. 
Published: July 2022

AbstractThe exoskeleton of spiders is the primary structure that interacts with the external mechanical stimuli, thus playing a crucial role in spider life. In particular, fangs, legs, and prosoma are the main rigid structures of the exoskeleton and their properties must be measured to better understand their mechanical behaviours. Here we investigate, by means of nanoindentation, the mechanical properties of the external sclerotized cuticles of such parts in the spider Harpactira curvipes. Interestingly, the results show that the leg’s cuticle is stiffer than the prosoma and has a stiffness similar to the one of the tip fangs. This could be explained by the legs’ function in perceiving vibrations that could be facilitated by higher stiffness. From a broader perspective, this characterization could help to understand how the same basic material (the cuticle, i.e. mainly composed of chitin) can be tuned to achieve different mechanical functions, which improves the animal’s adaptation to specific evolutive requirements. We, thus, hope that this work stimulates further comparative analysis. Moreover, these results may also be potentially important to inspire the design of graded materials with superior mechanical properties.
Nonlinear functional muscle network based on information theory tracks sensorimotor integration post stroke
Authors: O’Keeffe Rory , Shirazi Seyed Yahya , Bilaloglu Seda , Jahed Shayan , Bighamian Ramin , Raghavan Preeti , Atashzar S. Farokh 
Published: July 2022

AbstractSensory information is critical for motor coordination. However, understanding sensorimotor integration is complicated, especially in individuals with impairment due to injury to the central nervous system. This research presents a novel functional biomarker, based on a nonlinear network graph of muscle connectivity, called InfoMuNet, to quantify the role of sensory information on motor performance. Thirty-two individuals with post-stroke hemiparesis performed a grasp-and-lift task, while their muscle activity from 8 muscles in each arm was measured using surface electromyography. Subjects performed the task with their affected hand before and after sensory exposure to the task performed with the less-affected hand. For the first time, this work shows that InfoMuNet robustly quantifies changes in functional muscle connectivity in the affected hand after exposure to sensory information from
the less-affected side. > 90% of the subjects conformed with the improvement resulting from this sensory exposure. InfoMuNet also shows high sensitivity to tactile, kinesthetic, and visual input alterations at the subject level, highlighting its potential use in precision rehabilitation interventions.
Village and farm-level risk factors for avian influenza infection on backyard chicken farms in Bangladesh
Authors: Das Gupta Suman , Barua Brishti , Fournié Guillaume , Hoque Md. Ahasanul , Henning Joerg 
Published: July 2022

AbstractA cross-sectional study was conducted with 144 small-scale poultry farmers across 42 Bangladeshi villages to explore risk factors associated with avian influenza H5 and H9 seropositivity on backyard chicken farms. Using mixed-effects logistic regression with village as random effect, we identified crow abundance in garbage dumping places and presence of migratory wild birds within villages to be associated with higher odds of H5 and H9 seropositivity. At farm-level, garbage around poultry houses was also associated with higher odds of H5 and H9 seropositivity. In addition, specific trading practices (such as, purchase of chickens from live bird markets (LBM) and neighboring farms to raise them on their own farms, frequency of visits to LBM, purchase of poultry at LBM for consumption) and contact of backyard chickens with other animals (such as, feeding of different poultry species together, using pond water as drinking source for poultry, access of feral and wild animals to poultry houses) were associated with higher odds of H5 or H9 seropositivity. Resource-constrained small-scale poultry farmers should be able to address risk factors identified in this study without requiring large investments into poultry management, thereby reducing the likelihood of avian influenza virus transmission and ultimately occurrence of avian influenza outbreaks.
Diffuse correlation spectroscopy blood flow monitoring for intraventricular hemorrhage vulnerability in extremely low gestational age newborns
Authors: Sunwoo John , Zavriyev Alexander I. , Kaya Kutlu , Martin Alyssa , Munster Chelsea , Steele Tina , Cuddyer Deborah , Sheldon Yvonne , Orihuela-Espina Felipe , Herzberg Emily M. , Inder Terrie , Franceschini Maria Angela , El-Dib Mohamed 
Published: July 2022

AbstractIn premature infants with an extremely low gestational age (ELGA, < 29 weeks GA), dysregulated changes in cerebral blood flow (CBF) are among the major pathogenic factors leading to germinal matrix/intraventricular hemorrhage (GM/IVH). Continuous monitoring of CBF can guide interventions to minimize the risk of brain injury, but there are no clinically standard techniques or tools for its measurement. We report the feasibility of the continuous monitoring of CBF, including measures of autoregulation, via diffuse correlation spectroscopy (DCS) in ELGA infants using CBF variability and correlation with scalp blood flow (SBF, served as a surrogate measure of systemic perturbations). In nineteen ELGA infants (with 9 cases of GM/IVH) monitored for 6–24 h between days 2–5 of life, we found a strong correlation between CBF and SBF in severe IVH (Grade III or IV) and IVH diagnosed within 72 h of life, while CBF variability alone was not associated with IVH. The proposed method is potentially useful at the bedside for the prompt assessment of cerebral autoregulation and early identification of infants vulnerable to GM/IVH.