bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial and temporal changes in microbial communities and greenhouse gas emissions in a denitrifying woodchip bioreactor at low water temperatures
Authors: Hellman Maria , Juhanson Jaanis , Herbert Roger , Hallin Sara 
Published: April 2023

AbstractNitrogen (N) pollution is a major threat to ecosystems and a driver of climate change through emissions of the greenhouse gas nitrous oxide (N2O). Mining activities are increasingly recognized for contributing to N pollution due to undetonated, N-based explosives. A woodchip denitrifying bioreactor, installed to treat nitrate-rich leachate from waste rock dumps in northern Sweden, was monitored for two years to determine the spatial and temporal distribution of microbial communities in pore water and woodchips and their genetic potential for different N transformation processes, and how this affected the N removal capacity and possible production of undesired N species, like ammonium, nitrite and N2O. About 80 and 65 % of the nitrate was removed from the leachate the first and second operational year, respectively, which agreed with a decrease in dissolved organic carbon in the outlet water. There was a succession in the microbial community over time and in space along the reactor length in both pore water and woodchips, which was reflected in the genetic potential for N cycling and ultimately also reactor performance. We conclude that DNRA had minimal impact on the overall N removal efficiency due to the low relative abundance of the key genenrfAinvolved in DNRA and the low production of ammonium. However, nitrite, ammonium, and N2O were formed in the bioreactor and released in the effluent water, although direct emissions of N2O from the surface was low. The N2O production in the reactor might be explained by the ratio between the genetic potential for overall denitrification and N2O reduction in the woodchip and pore water communities, as indicated by the low ratio between the abundance ofnirandnosZgenes. Altogether, the results indicate that the denitrification pathway was temporally as well as spatially separated along the reactor length, and that unwanted reactive N species were produced at different time points and locations in the reactor. Thus, the succession of microbial communities in woodchip denitrifying bioreactors treating mining impacted water develops slowly at low temperature, which impacts the reactor performance.
Bcl-xL is translocated to the nucleus via CtBP2 to epigenetically promote metastasis
Authors: Zhang Tiantian , Li Sha , Tan Yingcai Adrian , Na Joseph HyungJoon , Chen Zhengming , Damle Priyadarshan , Chen Xiang , Choi Soyoung , Mishra Bikash , Wang Dunrui , Grossman Steven R. , Jiang Xuejun , Li Yi , Chen Yao-Tseng , Xiang Jenny Z. , Du Yi-Chieh Nancy 
Published: April 2023

AbstractBesides its mitochondria-based anti-apoptotic role, Bcl-xL also travels to the nucleus to promote cancer metastasis by upregulating global histone H3 trimethyl Lys4 (H3K4me3) and TGFβ transcription. How Bcl-xL is translocated into the nucleus and how nuclear Bcl-xL regulates H3K4me3 modification are not understood. Here, we report that C-terminal Binding Protein 2 (CtBP2) binds Bcl-xL via its N-terminus and translocates Bcl-xL into the nucleus. Knockdown of CtBP2 by shRNA decreases the nuclear portion of Bcl-xL and reverses Bcl-xL-induced cell migration and metastasis in mouse models. Furthermore, knockout of CtBP2 suppresses Bcl-xL transcription. The binding between Bcl-xL and CtBP2 is required for their interaction with MLL1, a histone H3K4 methyltransferase. Pharmacologic inhibition of MLL1 enzymatic activity reverses Bcl-xL-induced H3K4me3 and TGFβ mRNA upregulation as well as cell invasion. Moreover, cleavage under targets and release using nuclease (CUT&RUN) coupled with next generation sequencing reveals that H3K4me3 modifications are particularly enriched in the promotor region of genes encoding TGFβ and its signaling pathway in the cancer cells overexpressing Bcl-xL. Altogether, the metastatic function of Bcl-xL is mediated by its interaction with CtBP2 and MLL1.
Integrated analysis of spatial multi-omics with SpatialGlue
Authors: Long Yahui , Ang Kok Siong , Liao Sha , Sethi Raman , Heng Yang , Zhong Chengwei , Xu Hang , Husna Nazihah , Jian Min , Ng Lai Guan , Chen Ao , Gascoigne Nicholas RJ , Xu Xun , Chen Jinmiao 
Published: April 2023

AbstractIntegration of multiple data modalities in a spatially informed manner remains an unmet need for exploiting spatial multi-omics data. We introduce SpatialGlue, a graph neural network with dual-attention mechanism, to learn each modality’s significance at cross-omics and intra-omics integration. We demonstrate that SpatialGlue can accurately aggregate cell types into spatial domains at a higher resolution on different tissue types and technology platforms, as well as gain insights into cross-modality spatial correlations.
Gene Expression and Splicing QTL Analysis of Blood Cells in African American Participants from the Jackson Heart Study
Authors: Wen Jia , Sun Quan , Huang Le , Zhou Lingbo , Doyle Margaret F. , Ekunwe Lynette , Olson Nels C. , Reiner Alexander P. , Li Yun , Raffield Laura M. 
Published: April 2023

AbstractMost gene expression and alternative splicing quantitative trait loci (eQTL/sQTL) studies have been biased toward European ancestry individuals. Here, we performed eQTL and sQTL analysis using TOPMed whole genome sequencing-derived genotype data and RNA sequencing data from stored peripheral blood mononuclear cells in 1,012 African American participants from the Jackson Heart Study (JHS). At a false discovery rate (FDR) of 5%, we identified 4,798,604 significant eQTL-gene pairs, covering 16,538 unique genes; and 5,921,368 sQTL-gene-cluster pairs, covering 9,605 unique genes. About 31% of detected eQTL and sQTL variants with a minor allele frequency (MAF) > 1% in JHS were rare (MAF < 0.1%), and therefore unlikely to be detected, in European ancestry individuals. We also generated 17,630 eQTL credible sets and 24,525 sQTL credible sets for genes (gene-clusters) with lead QTL p < 5e-8. Finally, we created an open database, which is freely available online, allowing fast query and bulk download of our QTL results.
Surfaces: A software to quantify and visualize interactions within and between proteins and ligands
Authors: Teruel Natália , Borges Vinicius Magalhães , Najmanovich Rafael 
Published: April 2023

AbstractComputational methods for the quantification and visualization of the relative contribution of molecular interactions to the stability of biomolecular structures and complexes are fundamental to understand, modulate and engineer biological processes. Here we present Surfaces, an easy to use, fast and customizable software for quantification and visualization of molecular interactions based on the calculation of surface areas in contact. Surfaces calculations shows equivalent levels of correlations with experimental data as computationally expensive methods based on molecular dynamics. All scripts are available athttps://github.com/nataliateruel/SurfacesDocumentation is available athttps://surfaces-tutorial.readthedocs.io/en/latest/index.html
Eccentric contraction response of stimulated skeletal muscle fascicle at the various strain rates and stimulation timing
Authors: Tran Dat Trong , Tsai Liren 
Published: April 2023

AbstractMuscle injuries are the most common sports injuries, and it is often observed in eccentric contraction. There are many factors that could influence the severity of muscle injuries, including strain and strain rate. This study evaluated the interaction of these two factors on the biomechanical properties of the muscle-tendon bundle and their role in injuries. A Hopkinson bar system, an MTS machine and an electrical pulse generator were utilized to collect eccentric contraction response data of over 150 frog muscle-tendon samples at strain rates ranging from 0.01 to 300 s-1. The results have shown that the maximum stress has increased and peaked at about 150 s-1. That peak value has then maintained at the following strain rates. While Young’s modulus of stimulated samples reduced as the strain rate changed from 50 to 300 s-1. That trend was in contrast to unstimulated muscle bundles. In addition, strain rate has significantly influenced tendon-muscle bundle fracture. Samples tend to rupture at a minor strain of about 3.5 % with strain rates over 200 s-1. Because of the increasing stiffness of the muscle area at high strain rates, increased strain in the tendon region resulted in frequent injuries in the tendon area. On the other hand, a maximum-stress reduction was detected when the muscle bundles were stimulated at muscle strain greater than 0.2. The results showed that improper timing of stimulation could increase muscle injury.
Evaluation of the Pilot Wastewater Surveillance for SARS-CoV-2 in Norway, June 2022 – March 2023
Authors: Amato Ettore , Hyllestad Susanne , Heradstveit Petter , Langlete Petter , Moen Line Victoria , Rohringer Andreas , Pires João , Baz Lomba Jose Antonio , Bragstad Karoline , Feruglio Siri Laura , Aavitsland Preben , Madslien Elisabeth Henie 
Published: May 2023

AbstractBackgroundDuring the COVID-19 pandemic, wastewater-based surveillance gained great international interest as an additional tool to monitor SARS-CoV-2. In autumn 2021, the Norwegian Institute of Public Health decided to pilot a national wastewater surveillance (WS) system for SARS-CoV-2 and its variants between June 2022 and March 2023. We evaluated the system to assess if it met its objectives and its attribute-based performance.MethodsWe adapted the available guidelines for evaluation of surveillance systems. The evaluation was carried out as a descriptive analysis and consisted of the following three steps: (i) description of the WS system, (ii) identification of users and stakeholders, and (iii) analysis of the system’s attributes and performance including sensitivity, specificity, timeliness, usefulness, representativeness, simplicity, flexibility, stability, and communication. Cross-correlation analysis was performed to assess the system’s ability to provide early warning signal of new wave of infections.ResultsThe pilot WS system was a national surveillance system using existing wastewater infrastructures from the largest Norwegian municipalities. We found that the system was sensitive, timely, useful, representative, simple, flexible, acceptable, and stable to follow the general trend of infection. Preliminary results indicate that the system could provide an early signal of changes in variant distribution. However, challenges may arise with: (i) specificity due to temporary fluctuations of RNA levels in wastewater, (ii) representativeness when downscaling, and (iii) flexibility and acceptability when upscaling the system due to limited resources and/or capacity.ConclusionsOur results showed that the pilot WS system met most of its surveillance objectives. The system was able to provide an early warning signal of 1-2 weeks, and the system was useful to monitor infections at population level and complement routine surveillance when individual testing activity was low. However, temporary fluctuations of WS values need to be carefully interpreted. To improve quality and efficiency, we recommend to standardise and validate methods for assessing trends of new waves of infection and variants, evaluate the WS system using a longer operational period particularly for new variants, and conduct prevalence studies in the population to calibrate the system and improve data interpretation.
Highly Potent Peptide Therapeutics To Prevent Protein Aggregation In Huntington’s Disease
Authors: Khan Anooshay , Yuca Esra , Özçelik Cemile Elif , Begli Ozge , Oguz Oguzhan , Kasırga Serkan , Seker Urartu Ozgur Safak 
Published: April 2023

ABSTRACTHuntington’s disease (HD) is a progressive, autosomal dominant neurodegenerative disorder resulting from a significant amplification of CAG repeats in exon 1 of the Huntingtin (Htt) gene. More than 36 CAG repeats result in the formation of mutant Htt (mHtt) protein. These amino-terminal mHtt fragments lead to the formation of misfolded proteins, which then form aggregates in relevant brain regions. Available treatments concentrate primarily on alleviating the disease’s symptoms. Therefore, therapies that can delay the progression of the disease are imperative to halt the course of the disease. Peptide-based drug therapies provide such a platform. Inhibitory peptides were screened against monomeric units of both wild type (Htt(Q25)) and mHtt fragments, including Htt(Q46)and Htt(Q103). It was accomplished by utilizing several display technologies. This study focuses on the in-vitro characterization of the screened peptides. Fibril kinetics was studied in real-time utilizing the Thioflavin T (ThT) assay. The impact of specific peptides on fibril formation was examined by observing the change in fluorescence signal. Atomic force microscopy was also used to study the influence of peptides on fibril formation. Three of the six chosen peptides (HHGANSLSLVSQD, HGLHSMHNKLTR, and WMFPSLKLLDYH) effectively inhibited aggregation. These experiments demonstrate that the chosen peptides suppress the formation of fibrils in mHtt proteins and can provide a therapeutic lead for further optimization and development.
Generation of parthenocarpic tomato plants in multiple elite cultivars using the CRISPR/Cas9 system
Authors: Nguyen Cam Chau , Vu Tien Van , Shelake Rahul Mahadev , Nguyen Nhan Thi , Khanh Tran Dang , Kim Jae-Yean 
Published: April 2023

AbstractTomato (Solanum lycopersicumL.) is one of the most important crops in the world for its fruit production. Advances in cutting-edge techniques have enabled the development of numerous critical traits related to the quality and quantity of tomatoes. Genetic engineering techniques, such as gene transformation and gene editing, have emerged as powerful tools for generating new plant varieties with superior traits. In this study, we induced parthenocarpic traits in a population of elite tomato (ET) lines. At first, the adaptability of ET lines to genetic transformation was evaluated to identify the best-performing lines by transforming theSlANT1gene overexpression cassette and then later used to produce theSlIAA9knockout lines using the CRISPR/Cas9 system. ET5 and ET8 emerged as excellent materials for these techniques and showed higher efficiency. Typical phenotypes of knockoutsliaa9were clearly visible in G0 and G1 plants, in which simple leaves and parthenocarpic fruits were observed. The high efficiency of the CRISPR/Cas9 system in developing new tomato varieties with desired traits in a short period was demonstrated by generating T-DNA-free homozygoussliaa9knockout plants in the G1 generation. Additionally, a simple artificial fertilization method was successfully applied to recover seed production from parthenocarpic plants, securing the use of these varieties as breeding materials.
Aging-associated Decline in Vascular Smooth Muscle Cell Mechanosensation is Mediated by Piezo1 Channel
Authors: Luu Ngoc , Bajpai Apratim , Li Rui , Park Seojin , Noor Mahad , Ma Xiao , Chen Weiqiang 
Published: April 2023

AbstractAging of the vasculature is associated with detrimental changes in vascular smooth muscle cell (VSMC) mechanosensitivity to extrinsic forces in their surrounding microenvironment. However, how chronological aging alters VSMCs’ ability to sense and adapt to mechanical perturbations remains unexplored. Here, we show defective VSMC mechanosensation in aging measured with ultrasound tweezers-based micromechanical system, force instantaneous frequency spectrum and transcriptome analyses. The mechanobiological study reveals that aged VSMCs adapt a relatively inert solid-like state with altered actin cytoskeletal integrity, resulting in an impairment in their mechanosensitivity and dynamic mechanoresponse to mechanical perturbations. The aging-associated decline in mechanosensation behaviors is mediated by hyperactivity of Piezo1-dependent calcium signaling. Inhibition of Piezo1 alleviates vascular aging and partially restores the loss in dynamic contractile properties in aged cells. Altogether, our study reveals the novel signaling pathway underlying aging-associated aberrant mechanosensation in VSMC and identifies Piezo1 as a potential therapeutic mechanobiological target to alleviate vascular aging.
Rapid appearance of negative emotion during oral fentanyl self-administration in male and female rats
Authors: Coffey Kevin R. , Nickelson William , Dawkins Aliyah J. , Neumaier John F. 
Published: April 2023

AbstractOpioid use disorder has become an epidemic in the United States, fueled by the widespread availability of fentanyl, which produces rapid and intense euphoria followed by severe withdrawal and emotional distress. We developed a new preclinical model of fentanyl seeking in outbred male and female rats using volitional oral self-administration that can be readily applied in labs without intravascular access. Using a traditional two lever operant procedure, rats learned to take oral fentanyl vigorously, escalated intake across sessions, and readily reinstated responding to conditioned cues after extinction. Oral self-administration also revealed individual and sex differences that are essential to studying substance use risk propensity. During a behavioral economics task, rats displayed inelastic demand curves and maintained stable intake across a wide range of fentanyl concentrations. Oral SA was also neatly patterned, with distinct “ loading” and “ maintenance” phases of responding within each session. Using our software DeepSqueak, we analyzed thousands of ultrasonic vocalizations (USVs), which are innate expressions of current emotional state in rats. Rats produced 50 kHz USVs during loading then shifted quickly to 22 kHz calls despite ongoing maintenance oral fentanyl taking, reflecting a transition to negative reinforcement. Using fiber photometry, we found that the lateral habenula differentially processed drug-cues and drug-consumption depending on affective state, with potentiated modulation by drug cues and consumption during the negative affective maintenance phase. Together, these results indicate a rapid progression from positive to negative reinforcement occurs even within an active drug taking session, revealing a within-session opponent process.Significance StatementThe United States opioid epidemic is defined by rampant and treatment resistant fentanyl use. Better understanding of neural substrates underlying this phenomenon is essential to slowing the opioid crisis. Intravenous and vapor self-administration (SA) are the standard models for studying fentanyl use in rodents, however they many carry pragmatic downsides. Here, we used a novel oral fentanyl self-administration model that provides key translational and technical benefits and can be readily applied in other labs to study the neurobiology of fentanyl SA. This method captured individual and sex differences necessary for studying substance use risk propensity and uncovered a rapid shift in affective state in rats, suggesting and shift from positive to negative reinforcement within each fentanyl taking session.
Homeostatic Regulation of Seizure Susceptibility and Cognitive Function by Derlin-1 through Maintenance of Adult Neurogenesis
Authors: Murao Naoya , Matsuda Taito , Kadowaki Hisae , Matsushita Yosuke , Tanimoto Kousuke , Katagiri Toyomasa , Nakashima Kinichi , Nishitoh Hideki 
Published: April 2023

AbstractDysfunction of organelle is closely associated with neurological diseases involving disruption of adult neurogenesis. However, the role of the endoplasmic reticulum (ER)-related molecules in this process remains largely unexplored. Here we show that Derlin-1, an ER quality controller, maintains adult neurogenesis in a spatiotemporal manner. Deletion of Derlin-1 in the mouse central nervous system induces ectopic localization of newborn neurons and impairs neural stem cells (NSCs) transition from active to quiescent states, resulting in early depletion of hippocampal NSCs. As a result, Derlin-1- deficient mice exhibit phenotypes of increased seizure susceptibility and impaired cognitive function. Reduced expression of signal transducer and activator of transcription 5b (Stat5b) was found to be responsible for the impairment of adult neurogenesis in Derlin-1-deficient NSCs. Remarkably, the inhibition of histone deacetylase activity ameliorated seizure susceptibility and cognitive dysfunction in Derlin-1-deficient mice by increasing Stat5b expression and restoring abnormal neurogenesis. Overall, our findings demonstrate that Derlin-1, as its characteristic function, plays an essential role in the homeostasis of adult neurogenesis via Stat5b expression, thus regulating seizure susceptibility and cognitive function.
Sex Differences in Sleep Phenotypes in the BACHD Mouse Model of Huntington’s Disease
Authors: Chiem Emily , Zhao Kevin , Stark Gemma , Ghiani Cristina A. , Colwell Christopher S. , Paul Ketema N. 
Published: April 2023

AbstractSleep and circadian rhythm disturbances are common features of Huntington’s disease (HD). HD is an autosomal dominant neurodegenerative disorder that affects men and women in equal numbers, but some epidemiological studies as well as preclinical work indicate there may be sex differences in disease progression. Since sex differences in HD could provide important insights to understand cellular and molecular mechanism(s), we used the bacterial artificial chromosome transgenic mouse model of HD (BACHD) to examine whether sex differences in sleep/wake cycles are detectable in an animal model of the disease. Electroencephalography/electromyography (EEG/EMG) was used to measure sleep/wake states and polysomnographic patterns in young adult (12 week-old) male and female wild-type and BACHD mice. Our findings show that male, but not female, BACHD mice exhibited increased variation in phases of the rhythms as compared to age and sex matched wild-types. For both Rapid-eye movement (REM) and Non-rapid eye movement (NREM) sleep, genotypic and sex differences were detected. In particular, the BACHD males spent less time in NREM and exhibited a more fragmented sleep than the other groups. Both male and female BACHD mice exhibited significant changes in delta but not in gamma power compared to wild-type mice. Finally, in response to a 6-hrs sleep deprivation, both genotypes and sexes displayed predicted homeostatic responses to sleep loss. These findings suggest that females are relatively protected early in disease progression in this HD model.Significance StatementSleep and circadian rhythm disturbances are common features of Huntington’s disease (HD). Using an animal model of HD and EEG measures of sleep, we found that the males were more vulnerable to sleep/wake architecture alterations and sleep fragmentation. Homeostatic recovery from sleep loss did not appear to be altered at this stage of the disease. These findings raise the possibility that sex-specific factors play a role in the HD symptom progression and that hormone-based treatments may have therapeutic utility.