bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancers regulate 3′ end processing activity to control expression of alternative 3′UTR isoforms
Authors: Kwon Buki , Fansler Mervin M. , Patel Neil D. , Lee Jihye , Ma Weirui , Mayr Christine 
Published: May 2022

AbstractMulti-UTR genes are widely transcribed and express their alternative 3′UTR isoforms in a cell type-specific manner. As transcriptional enhancers regulate mRNA expression, we investigated if they also regulate 3′UTR isoform expression. Endogenous enhancer deletion of the multi-UTR gene PTEN did not impair transcript production but prevented 3′UTR isoform switching which was recapitulated by silencing of an enhancer-bound transcription factor. In reporter assays, enhancers increase transcript production when paired with single-UTR gene promoters. However, when combined with multi-UTR gene promoters, they change 3′UTR isoform expression by increasing 3′ end processing activity of polyadenylation sites. Processing activity of polyadenylation sites is affected by transcription factors, including NF-κB and MYC, transcription elongation factors, chromatin remodelers, and histone acetyltransferases. As endogenous cell type-specific enhancers are associated with genes that increase their short 3′UTRs in a cell type-specific manner, our data suggest that transcriptional enhancers integrate cellular signals to regulate cell type-and condition-specific 3′UTR isoform expression.
High-throughput predictions of metal–organic framework electronic properties: theoretical challenges, graph neural networks, and data exploration
Authors: Rosen Andrew S. , Fung Victor , Huck Patrick , O’Donnell Cody T. , Horton Matthew K. , Truhlar Donald G. , Persson Kristin A. , Notestein Justin M. , Snurr Randall Q. 
Published: May 2022

AbstractWith the goal of accelerating the design and discovery of metal–organic frameworks (MOFs) for electronic, optoelectronic, and energy storage applications, we present a dataset of predicted electronic structure properties for thousands of MOFs carried out using multiple density functional approximations. Compared to more accurate hybrid functionals, we find that the widely used PBE generalized gradient approximation (GGA) functional severely underpredicts MOF band gaps in a largely systematic manner for semi-conductors and insulators without magnetic character. However, an even larger and less predictable disparity in the band gap prediction is present for MOFs with open-shell 3d transition metal cations. With regards to partial atomic charges, we find that different density functional approximations predict similar charges overall, although hybrid functionals tend to shift electron density away from the metal centers and onto the ligand environments compared to the GGA point of reference. Much more significant differences in partial atomic charges are observed when comparing different charge partitioning schemes. We conclude by using the dataset of computed MOF properties to train machine-learning models that can rapidly predict MOF band gaps for all four density functional approximations considered in this work, paving the way for future high-throughput screening studies. To encourage exploration and reuse of the theoretical calculations presented in this work, the curated data is made publicly available via an interactive and user-friendly web application on the Materials Project.
CUX2 deficiency causes facilitation of excitatory synaptic transmission onto hippocampus and increased seizure susceptibility to kainate
Authors: Suzuki Toshimitsu , Tatsukawa Tetsuya , Sudo Genki , Delandre Caroline , Pai Yun Jin , Miyamoto Hiroyuki , Raveau Matthieu , Shimohata Atsushi , Ohmori Iori , Hamano Shin-ichiro , Haginoya Kazuhiro , Uematsu Mitsugu , Takahashi Yukitoshi , Morimoto Masafumi , Fujimoto Shinji , Osaka Hitoshi , Oguni Hirokazu , Osawa Makiko , Ishii Atsushi , Hirose Shinichi , Kaneko Sunao , Inoue Yushi , Moore Adrian Walton , Yamakawa Kazuhiro 
Published: May 2022

AbstractCUX2 gene encodes a transcription factor that controls neuronal proliferation, dendrite branching and synapse formation, locating at the epilepsy-associated chromosomal region 12q24 that we previously identified by a genome-wide association study (GWAS) in Japanese population. A CUX2 recurrent de novo variant p.E590K has been described in patients with rare epileptic encephalopathies and the gene is a candidate for the locus, however the mutation may not be enough to generate the genome-wide significance in the GWAS and whether CUX2 variants appear in other types of epilepsies and physiopathological mechanisms are remained to be investigated. Here in this study, we conducted targeted sequencings of CUX2, a paralog CUX1 and its short isoform CASP harboring a unique C-terminus on 271 Japanese patients with a variety of epilepsies, and found that multiple CUX2 missense variants, other than the p.E590K, and some CASP variants including a deletion, predominantly appeared in patients with temporal lobe epilepsy (TLE). The CUX2 variants showed abnormal localization in human cell culture analysis. While wild-type CUX2 enhances dendritic arborization in fly neurons, the effect was compromised by some of the variants. Cux2- and Casp-specific knockout mice both showed high susceptibility to kainate, increased excitatory cell number in the entorhinal cortex, and significant enhancement in glutamatergic synaptic transmission to the hippocampus. CASP and CUX2 proteins physiologically bound to each other and co-expressed in excitatory neurons in brain regions including the entorhinal cortex. These results suggest that CUX2 and CASP variants contribute to the TLE pathology through a facilitation of excitatory synaptic transmission from entorhinal cortex to hippocampus.
Metagenomic psychrohalophilic xylanase from camel rumen investigated for bioethanol production from wheat bran using Bacillus subtilis AP
Authors: Rajabi Marzieh , Nourisanami Farahdokht , Ghadikolaei Kamran Khalili , Changizian Mohammad , Noghabi Kambiz Akbari , Zahiri Hossein Shahbani 
Published: May 2022

AbstractBioethanol produced from lignocellulosic biomass is regarded as a clean and sustainable energy source. The recalcitrant structure of lignocellulose is a major drawback to affordable bioethanol production from plant biomass. In this study, a novel endo-1,4-xylanase, named Xyn-2, from the camel rumen metagenome, was characterized and evaluated for hydrolysis of agricultural wastes. The enzyme was identified as a psychrohalophilic xylanase with maximum activity at 20 °C, keeping 58% of the activity at 0 °C, and exhibiting twice as much activity in 0.5–4 M NaCl concentrations. Xyn-2 was able to hydrolyze wheat bran (100%), sunflower-seed shell (70%), wheat straw (56%), rice straw (56%), and rice bran (41%), in the relative order of efficiency. Besides, the ethanologenic B. subtilis AP was evaluated without and with Xyn-2 for bioethanol production from wheat bran. The strain was able to produce 5.5 g/L ethanol with a yield of 22.6% in consolidated bioprocessing (CBP). The contribution of Xyn-2 to ethanol production of B. subtilis AP was studied in an SSF system (simultaneous saccharification and fermentation) giving rise to a significant increase in ethanol production (p ≤ 0.001) to a final concentration of 7.3 g/L with a yield of 26.8%. The results revealed that the camel rumen metagenome might be an invaluable source of novel xylanolytic enzymes with potential application in lignocellulosic biomass valorization. At the same time, the results suggest that B. subtilis with a diverse carbon-source preference and sophisticated systems for production and secretion of enzymes might be a promising candidate for strain development for bioethanol production from plant biomass. It might be assumed that the fortification of B. subtilis enzymatic arsenal with select xylanolytic enzymes from camel rumen metagenome may have a great impact on bioethanol production.
Expert surgeons and deep learning models can predict the outcome of surgical hemorrhage from 1 min of video
Authors: Pangal Dhiraj J. , Kugener Guillaume , Zhu Yichao , Sinha Aditya , Unadkat Vyom , Cote David J. , Strickland Ben , Rutkowski Martin , Hung Andrew , Anandkumar Animashree , Han X. Y. , Papyan Vardan , Wrobel Bozena , Zada Gabriel , Donoho Daniel A. 
Published: May 2022

AbstractMajor vascular injury resulting in uncontrolled bleeding is a catastrophic and often fatal complication of minimally invasive surgery. At the outset of these events, surgeons do not know how much blood will be lost or whether they will successfully control the hemorrhage (achieve hemostasis). We evaluate the ability of a deep learning neural network (DNN) to predict hemostasis control ability using the first minute of surgical video and compare model performance with human experts viewing the same video. The publicly available SOCAL dataset contains 147 videos of attending and resident surgeons managing hemorrhage in a validated, high-fidelity cadaveric simulator. Videos are labeled with outcome and blood loss (mL). The first minute of 20 videos was shown to four, blinded, fellowship trained skull-base neurosurgery instructors, and to SOCALNet (a DNN trained on SOCAL videos). SOCALNet architecture included a convolutional network (ResNet) identifying spatial features and a recurrent network identifying temporal features (LSTM). Experts independently assessed surgeon skill, predicted outcome and blood loss (mL). Outcome and blood loss predictions were compared with SOCALNet. Expert inter-rater reliability was 0.95. Experts correctly predicted 14/20 trials (Sensitivity: 82%, Specificity: 55%, Positive Predictive Value (PPV): 69%, Negative Predictive Value (NPV): 71%). SOCALNet correctly predicted 17/20 trials (Sensitivity 100%, Specificity 66%, PPV 79%, NPV 100%) and correctly identified all successful attempts. Expert predictions of the highest and lowest skill surgeons and expert predictions reported with maximum confidence were more accurate. Experts systematically underestimated blood loss (mean error − 131 mL, RMSE 350 mL, R20.70) and fewer than half of expert predictions identified blood loss > 500 mL (47.5%, 19/40). SOCALNet had superior performance (mean error − 57 mL, RMSE 295 mL, R20.74) and detected most episodes of blood loss > 500 mL (80%, 8/10). In validation experiments, SOCALNet evaluation of a critical on-screen surgical maneuver and high/low-skill composite videos were concordant with expert evaluation. Using only the first minute of video, experts and SOCALNet can predict outcome and blood loss during surgical hemorrhage. Experts systematically underestimated blood loss, and SOCALNet had no false negatives. DNNs can provide accurate, meaningful assessments of surgical video. We call for the creation of datasets of surgical adverse events for quality improvement research.
Questionnaire-based approach to evaluate the convenience of rechargeable extracorporeal pulse generators for wireless spinal cord stimulation
Authors: Hajiabadi Mohammad Mehdi , Jakobs Martin , Vicheva Petya , Unterberg Andreas , Ahmadi Rezvan 
Published: May 2022

AbstractSpinal cord stimulation (SCS) has been utilized for more than 50 years to treat refractory neuropathic pain. Currently, SCS systems with fully implantable pulse generators (IPGs) represent the standard. New wireless extracorporeal SCS (wSCS) devices without IPGs promise higher levels of comfort and convenience for patients. However, to date there are no studies on how charging and using this wSCS system affects patients and their therapy. This study is the first questionnaire-based survey on this topic focusing on patient experience. The trial was a single arm, open-label and mono-centric phase IV study. Standardized questionnaires were sent to all patients with a wSCS device in use at the time of trial. The primary endpoint was the convenience of the charging and wearing process scored on an ordinal scale from "very hard" (1) to "very easy" (5). Secondary endpoints included time needed for charging, the duration of stimulation per day and complication rates. Questionnaires of 6 out of 9 patients were returned and eligible for data analysis. The mean age of patients was 61.3 ± 6.7 (± SD) years. The duration of therapy was 20.3 ± 15.9 months (mean ± SD). The mean duration of daily stimulation was 17 ± 5.9 h (mean ± SD). n = 5 patients rated the overall convenience as "easy" (4) and n = 3 patients evaluated the effort of the charging process and wearing of the wSCS device as "low" (4). n = 5 patients considered the wearing and charging process as active participation in their therapy. n = 5 patients would choose an extracorporeal device again over a conventional SCS system. Early or late surgical complications did not occur in this patient collective. Overall, patients felt confident using extracorporeal wSCS devices without any complications. Effort to maintain therapy with this system was rated as low.
BRG1 is a biomarker of hypertrophic cardiomyopathy in human heart specimens
Authors: Scherba Jacob C. , Halushka Marc K. , Andersen Nicholas D. , Maleszewski Joseph J. , Landstrom Andrew P. , Bursac Nenad , Glass Carolyn 
Published: May 2022

AbstractHypertrophic cardiomyopathy (HCM) is a genetic disease of the sarcomere that causes otherwise unexplained cardiac hypertrophy and is associated with sudden death. While previous studies showed the role of the epigenetic modifier Brg1 in mouse models of HCM, additional work is needed to identify its role in humans. We tested the hypothesis that BRG1 expression is increased in periods of cardiac remodeling during fetal growth and in development of HCM. We employed immunohistochemical staining to evaluate protein expression of BRG1 in 796 human cardiac specimens (81 from patients with HCM) and describe elevated BRG1 expression in human fetal hearts in early development. In addition, we not only demonstrate increased expression of BRG1 in HCM, but we also show that other diseases that lead to heart failure have similar BRG1 expression to healthy controls. Inhibition of BRG1 in human induced pluripotent stem cell-derived cardiomyocytes significantly decreases MYH7 and increases MYH6, suggesting a regulatory role for BRG1 in the pathological imbalance of the two myosin heavy chain isoforms in human HCM. These data are the first demonstration of BRG1 as a specific biomarker for human HCM and provide foundation for future studies of epigenetics in human cardiac disease.
Terahertz absorption characteristics of ammonium salt solution based on self-sampling microfluidic chip
Authors: Meng Qinghao , Qian Siyu , Ding Jing , Li Qingjun , Zhao Xinyuan , Su Bo , Zhang Cunlin 
Published: May 2022

AbstractWith the continuous development of terahertz (THz) detection technology, the use of terahertz spectroscopy to study chemical samples has become one of the indispensable tools in the field of biochemistry. While most biomolecules biological activity can only be expressed in aqueous solutions, water as a polar molecule has strong absorption properties for terahertz waves, making it difficult to use terahertz technology to study the activity of biological samples in aqueous solutions. In this study, a sandwich-type terahertz microfluidic chip with high terahertz wave transmission was designed and combined with a terahertz time domain spectroscopy (THz-TDS) system to test the terahertz spectra of distilled water, 0.9 mol/L NH4Cl, (NH4)2SO4, (NH4)2CO3 and CH3COONH4 solutions, respectively, and to investigate the effect of the electric field action time on the hydrogen bond in the solution under the action of an external electric field. The experimental results show that the terahertz spectra of different ammonium solutions at the same concentration differ significantly, indicating that the ion hydration process affects the intermolecular hydrogen bonding in water, while the applied electric field also affects the hydrogen bonding in water, resulting in a change in the terahertz waves water absorption.
Characterization of NRPS and PKS genes involved in the biosynthesis of SMs in Alternaria dauci including the phytotoxic polyketide aldaulactone
Authors: Courtial Julia , Helesbeux Jean-Jacques , Oudart Hugo , Aligon Sophie , Bahut Muriel , Hamon Bruno , N’Guyen Guillaume , Pigné Sandrine , Hussain Ahmed G. , Pascouau Claire , Bataillé-Simoneau Nelly , Collemare Jérôme , Berruyer Romain , Poupard Pascal 
Published: May 2022

AbstractAlternaria dauci is a Dothideomycete fungus, causal agent of carrot leaf blight. As a member of the Alternaria genus, known to produce a lot of secondary metabolite toxins, A. dauci is also supposed to synthetize host specific and non-host specific toxins playing a crucial role in pathogenicity. This study provides the first reviewing of secondary metabolism genetic basis in the Alternaria genus by prediction of 55 different putative core genes. Interestingly, aldaulactone, a phytotoxic benzenediol lactone from A. dauci, was demonstrated as important in pathogenicity and in carrot partial resistance to this fungus. As nothing is known about aldaulactone biosynthesis, bioinformatic analyses on a publicly available A. dauci genome data set that were reassembled, thanks to a transcriptome data set described here, allowed to identify 19 putative secondary metabolism clusters. We exploited phylogeny to pinpoint cluster 8 as a candidate in aldaulactone biosynthesis. This cluster contains AdPKS7 and AdPKS8, homologs with genes encoding a reducing and a non-reducing polyketide synthase. Clusters containing such a pair of PKS genes have been identified in the biosynthesis of resorcylic acid lactones or dihydroxyphenylacetic acid lactones. AdPKS7 and AdPKS8 gene expression patterns correlated with aldaulactone production in different experimental conditions. The present results highly suggest that both genes are responsible for aldaulactone biosynthesis.
Inactivation of SARS-CoV-2 by a chitosan/α-Ag2WO4 composite generated by femtosecond laser irradiation
Authors: Pereira Paula Fabiana Santos , de Paula e Silva Ana Carolina Alves , da Silva Pimentel Bruna Natália Alves , Pinatti Ivo Mateus , Simões Alexandre Zirpoli , Vergani Carlos Eduardo , Barreto-Vieira Débora Ferreira , da Silva Marcos Alexandre Nunes , Miranda Milene Dias , Monteiro Maria Eduarda Santos , Tucci Amanda , Doñate-Buendía Carlos , Mínguez-Vega Gladys , Andrés Juan , Longo Elson 
Published: May 2022

AbstractIn the current COVID-19 pandemic, the next generation of innovative materials with enhanced anti-SARS-CoV-2 activity is urgently needed to prevent the spread of this virus within the community. Herein, we report the synthesis of chitosan/α-Ag2WO4 composites synthetized by femtosecond laser irradiation. The antimicrobial activity against Escherichia coli, Methicilin-susceptible Staphylococcus aureus (MSSA), and Candida albicans was determined by estimating the minimum inhibitory concentration (MIC) and minimal bactericidal/fungicidal concentration (MBC/MFC). To assess the biocompatibility of chitosan/α-Ag2WO4 composites in a range involving MIC and MBC/MFC on keratinocytes cells (NOK-si), an alamarBlue™ assay and an MTT assay were carried out. The SARS-CoV-2 virucidal effects was analyzed in Vero E6 cells through viral titer quantified in cell culture supernatant by PFU/mL assay. Our results showed a very similar antimicrobial activity of chitosan/α-Ag2WO4 3.3 and 6.6, with the last one demonstrating a slightly better action against MSSA. The chitosan/α-Ag2WO4 9.9 showed a wide range of antimicrobial activity (0.49–31.25 µg/mL). The cytotoxicity outcomes by alamarBlue™ revealed that the concentrations of interest (MIC and MBC/MFC) were considered non-cytotoxic to all composites after 72 h of exposure. The Chitosan/α-Ag2WO4 (CS6.6/α-Ag2WO4) composite reduced the SARS-CoV-2 viral titer quantification up to 80% of the controls. Then, our results suggest that these composites are highly efficient materials to kill bacteria (Escherichia coli, Methicillin-susceptible Staphylococcus aureus, and the yeast strain Candida albicans), in addition to inactivating SARS-CoV-2 by contact, through ROS production.
Controlling the characteristics of injected and accelerated electron bunch in corrugated plasma channel by temporally asymmetric laser pulses
Authors: Sedaghat M. , Amouye Foumani A. , Niknam A. R. 
Published: May 2022

AbstractIn laser-driven plasma wakefield accelerators, the accelerating electric field is orders of magnitude stronger than in conventional radio-frequency particle accelerators, but the dephasing between the ultrarelativistic electron bunch and the wakefield traveling at the group velocity of the laser pulse puts a limit on the energy gain. Quasi-phase-matching, enabled by corrugated plasma channels, is a technique for overcoming the dephasing limitation. The attainable energy and the final properties of accelerated electron beams are of utmost importance in laser wakefield acceleration (LWFA). In this work, using two-dimensional particle-in-cell simulations, the effect of the driving pulse duration on the performance of quasi-phase-matched laser wakefield acceleration (QPM-LWFA) is investigated. It is observed that for a pulse duration around half the plasma period, the maximum energy gain of the beam electrons finds its peak value. However, the results show that for a pulse of that duration the collimation of the bunch is much worse, compared to the case where the pulse duration is twice as long. Furthermore, the dynamics of the laser pulse and the evolution of the quality of the externally-injected electron bunch are studied for a symmetric pulse with sine-squared temporal profile, a positive skew pulse (i.e., one with sharp rise and slow fall), and a negative skew pulse (i.e., one with a slow rise and sharp fall). The results indicate that for a laser pulse with an appropriate pulse length compared with the plasma wavelength, the wakefield amplitude can be greatly enhanced by using a positive skew pulse, which leads to higher energy gain. Initially, this results from the stronger ponderomotive force associated with a fast rise time. Later, due to the distinct evolution of the three pulses with different initial profiles, the wakefield excited by the positive skew pulse becomes even stronger. In our simulations, the maximum energy gain for the asymmetric laser pulse with a fast rise time is almost two times larger than for the temporally symmetric laser pulse. Nevertheless, stronger focusing and defocusing fields are generated as well if a positive skew pulse is applied, which degrade the collimation of the bunch. These results should be taken into account in the design of miniature particle accelerators based on QPM-LWFA.