bluuebunny/crossref_metadata_2025 huggingface dataset:
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

With 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

CUX2 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

Bioethanol 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

Major 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

Spinal 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

Hypertrophic 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

With 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

Alternaria 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

In 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

In 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.
Prevalence and risk factors for depression among training physicians in China and the United States
Authors: Chen Lihong , Zhao Zhuo , Wang Zhen , Zhou Ying , Zhou Xin , Pan Hui , Shen Fengtao , Zeng Suhua , Shao Xinhua , Frank Elena , Sen Srijan , Li Weidong , Burmeister Margit
Published: May 2022

During their first year of medical residency (internship), 35% of training physicians in the United States suffer at least one depression episode. We assessed whether there is a similar increase of depression among first year residents in China, and identified predictors of depression in the two systems. 1006 residents across three cohorts (2016–2017, 2017–2018 and 2018–2019) at Shanghai Jiao Tong University and Peking Union Medical College were assessed in parallel with three cohorts of 7028 residents at 100 + US institutions. The Patient Health Questionnaire-9 (PHQ-9) depressive symptoms were measured at baseline and quarterly. Demographic, personal and residency factors were assessed as potential predictors of PHQ-9 depression scores. Similar to training interns in the US, the proportion of participants in China who met depression criteria at least once during the first year of residency increased substantially, from 9.1 to 35.1%. History of depression and symptoms at baseline were common factors significantly associated with depression during residency. By contrast, neuroticism, early family environment, female gender and not being coupled were associated with depression risk only in the US, while young age was a predictor of depression only in China. Fear of workplace violence also was a predictor in China. Long duty hours and reduced sleep duration emerged as training predictors of depression in both countries. The magnitude of depression increase and work-related drivers of depression were similar between China and the US, suggesting a need for effective system reforms in both systems.
Modeling neuron growth using isogeometric collocation based phase field method
Authors: Qian Kuanren , Pawar Aishwarya , Liao Ashlee , Anitescu Cosmin , Webster-Wood Victoria , Feinberg Adam W. , Rabczuk Timon , Zhang Yongjie Jessica
Published: May 2022

We present a new computational framework of neuron growth based on the phase field method and develop an open-source software package called “NeuronGrowth_IGAcollocation”. Neurons consist of a cell body, dendrites, and axons. Axons and dendrites are long processes extending from the cell body and enabling information transfer to and from other neurons. There is high variation in neuron morphology based on their location and function, thus increasing the complexity in mathematical modeling of neuron growth. In this paper, we propose a novel phase field model with isogeometric collocation to simulate different stages of neuron growth by considering the effect of tubulin. The stages modeled include lamellipodia formation, initial neurite outgrowth, axon differentiation, and dendrite formation considering the effect of intracellular transport of tubulin on neurite outgrowth. Through comparison with experimental observations, we can demonstrate qualitatively and quantitatively similar reproduction of neuron morphologies at different stages of growth and allow extension towards the formation of neurite networks.
Assessment of major centelloside ratios in Centella asiatica accessions grown under identical ecological conditions, bioconversion clues and identification of elite lines
Authors: Kunjumon Renju , Johnson Anil John , Sukumaryamma Remadevi Rajani Kurup , Baby Sabulal
Published: May 2022

Centellosides viz., asiatic acid, madecassic acid, asiaticoside, madecassoside, are the major bioactive molecules in Centella asiatica. In this study madecassic acid:asiatic acid, madecassoside:asiaticoside (C6-hydroxylation versus non-hydroxylation) and asiaticoside:asiatic acid, madecassoside:madecassic acid (C28-glycoside versus aglycone) ratios in 50 C. asiatica accessions originally collected from their natural habitats in south India and grown under identical ecological conditions for six generations were determined using validated HPTLC-densitometry protocols. Asiatic acid, madecassic acid, asiaticoside and madecassoside contents ranged from 0.00–0.29% (average 0.03 ± 0.06%; 28 accessions recorded asiatic acid content as zero), 0.02–0.72% (0.12 ± 0.13%), 0.04–2.41% (0.44 ± 0.52%) and 0.15–5.27% (1.59 ± 1.26%), respectively. Distinctly, C6-hydroxylated (madecassic acid:asiatic acid 4.00, madecassoside:asiaticoside 3.61) and C28-glycosylated (asiaticoside:asiatic acid 14.67, madecassoside: madecassic acid 13.25) centellosides dominated over the respective non-derivatized entities. Our results infer that both C6-hydroxylation by CYP450-dependent monooxygenases and C28-glycosylation by UDP-Glc glucosyltransferases are dominant bioconversion steps in C. asiatica. Besides, this study discovered six elite lines of C. asiatica, with their (asiaticoside + madecassoside) contents above the industrial benchmark (≥ 4%) from south India. Two elite clones with asiaticoside contents ≥ 2% were also identified. Standardization of the agrotechniques of these elite lines could lead to their industrial applications. Further, this study emphasizes the need for standardizing all four centellosides as biomarkers in C. asiatica raw drugs, pharmaceutical and cosmetic products.
Nuclear RNA transcript levels modulate nucleocytoplasmic distribution of ALS/FTD-associated protein FUS
Authors: Tsai Yueh-Lin , Mu Yu Chun , Manley James L.
Published: May 2022

Fused in Sarcoma (FUS) is a nuclear RNA/DNA binding protein that mislocalizes to the cytoplasm in the neurodegenerative diseases ALS and FTD. Despite the existence of FUS pathogenic mutations that result in nuclear import defects, a subset of ALS/FTD patients display cytoplasmic accumulation of wild-type FUS, although the underlying mechanism is unclear. Here we confirm that transcriptional inhibition, specifically of RNA polymerase II (RNAP II), induces FUS cytoplasmic translocation, but we show that several other stresses do not. We found unexpectedly that the epitope specificity of different FUS antibodies significantly affects the apparent FUS nucleocytoplasmic ratio as determined by immunofluorescence, explaining inconsistent observations in previous studies. Significantly, depletion of the nuclear mRNA export factor NXF1 or RNA exosome cofactor MTR4 promotes FUS nuclear retention, even when transcription is repressed, while mislocalization was independent of the nuclear protein export factor CRM1 and import factor TNPO1. Finally, we report that levels of nascent RNAP II transcripts, including those known to bind FUS, are reduced in sporadic ALS iPS cells, linking possible aberrant transcriptional control and FUS cytoplasmic mislocalization. Our findings thus reveal that factors that influence accumulation of nuclear RNAP II transcripts modulate FUS nucleocytoplasmic homeostasis, and provide evidence that reduced RNAP II transcription can contribute to FUS mislocalization to the cytoplasm in ALS.
Retinal drusen in glomerulonephritis with or without immune deposits suggest systemic complement activation in disease pathogenesis
Authors: Harraka P. , Mack H. , Colville D. , Barit D. , Langsford D. , Pianta T. , Ierino F. , Savige Judy
Published: May 2022

Retinal drusen are characteristic of macular degeneration and complement activation, but also occur in C3, lupus and IgA nephropathy. This cross-sectional observational study compared drusen counts in different forms of glomerulonephritis. Consecutive individuals with glomerulonephritis attending a general renal or transplant clinic underwent retinal imaging with a non-mydriatic camera. Drusen were counted in deidentified images by trained graders, compared with matched hospital patients, and correlated with clinical features. Eighty-four individuals with glomerulonephritis had a mean drusen count of 10 ± 27 compared with 3 ± 8 in hospital controls (p = 0.007). Fourteen individuals with glomerulonephritis (17%) and 4 hospital controls (4/49, 8%) had increased drusen counts (≥ 10) (p = 0.20). Increased drusen counts ≥ 10 were present in 13 (13/63, 21%)  of those with glomerulonephritis and immune deposits [membranous (n = 8), antiglomerular basement membrane nephritis (n = 6), FSGS (n = 49)], and one of the 21 (5%) with glomerulonephritis without immune deposits [ANCA-associated (n = 15), minimal change disease (n = 6)]. In antibody-mediated glomerulonephritis (n = 14), mean drusen counts were 2 ± 3 in individuals with normal kidney function, 16 ± 41 with impaired function and 5 ± 7 with kidney failure . Mean counts were 24 ± 56 in individuals with glomerular IgG deposits and 1 ± 1 in those without (p = 0.76), and 23 ± 60 with complement deposits and 4 ± 8 in those without. Drusen counts were also less in immunosuppressed individuals (p = 0.049). The demonstration of retinal drusen in some forms of glomerulonephritis is consistent with systemic complement activation, and suggests that treatment targeting the complement pathways is worthwhile.
Spatio-temporal evolution and driving factors of carbon storage in the Western Sichuan Plateau
Authors: Xiang Mingshun , Wang Chunjian , Tan Yuxiang , Yang Jin , Duan Linsen , Fang Yanni , Li Wenheng , Shu Yang , Liu Mengli
Published: May 2022

The carbon sequestration function of the ecosystem is one of the most important functions of ecosystem service, and it of great significance to study the spatio-temporal differentiation of carbon storage for promoting regional sustainable development. Ecosystems on the Western Sichuan Plateau are highly variable, but its spatio-temporal differentiation and driving factors are not yet clear. In this study, on the basis of land use monitoring data, meteorological and demographic data interpreted from Landsat remote sensing image, and through GIS analysis tools, the carbon storage module of InVEST (Integrated Valuation of Ecosystem Services and Trade-offs) model was used to estimate carbon storage and geodetector was used to detect the driving factors of carbon storage spatial differentiation. The results show that: (1) The carbon storage increased to 1.2455 × 1010 t from 1.2438 × 1010 t in the past 20 years, the ecosystem developed in a healthy way overall. (2) Carbon storage show High-High and Low-Low aggregation characteristics, but the area decreased by 1481.81 km2 and 311.11 km2 respectively, and the spatial cluster effect gradually weakened. (3) HAI is the leading factor causing the spatio-temporal differentiation of regional carbon storage, followed by temperature and NDVI; the interaction between factors significantly enhances the spatial differentiation of carbon storage, indicating that the change of carbon storage is the result of the joint action of natural and socioeconomic factors. The results of the study provide some theoretical basis for the development of differentiated ecological regulation models and strategies, and help to promote high-quality regional development.
Seasonal changes and decrease of suicides and suicide attempts in France over the last 10 years
Authors: Ambar Akkaoui Marine , Chan-Chee Christine , Laaidi Karine , Fifre Gregory , Lejoyeux Michel , Vaiva Guillaume , Peyre Hugo , Geoffroy Pierre A.
Published: May 2022

The objective of this study was to examine the evolution of suicides and suicide attempts over the last 10 years in France. We analyzed the number of deaths by suicide and suicide attempts in metropolitan France (2009–2018) from French national databases, on a daily, weekly or monthly basis. Seasonal variation in suicide rates was modeled using a cosinor function. Based on this model, we determined the association of suicides and suicide attempts with geographic characteristics, age, gender, means used and psychiatric disorders. The number of suicides and suicide attempts decreased over the last ten years in France (mean decrease of 14.49% and 11.69% per year). We observed a significant and recurrent seasonal pattern of suicides and suicide attempts in France, with a peak in spring. The suicide and suicide attempt rates were higher in the northern departments of France. Suicides were more frequent for men (75%) and middle-age individuals (45–54 years old), while suicide attempts were more frequent for women (62%) and young adults and middle-age individual (15–19 and 40–49 years old). Nearly two-thirds of the patients who attempted suicide suffered from comorbid psychiatric disorders. Mood disorders was the most frequent comorbid psychiatric disorder (54%). Voluntary drug intoxication was the most common means of suicide attempt (80%), and hanging was the most common means of suicide (54%). The number of suicides and suicide attempts decreased in France over the last 10 years, with large and recurrent seasonal variations. These findings could be used to alert and adjust prevention policies, as well as developing preventive strategies such as chronotherapeutics.
Superposition of vortex beams generated by polarization conversion in uniaxial crystals
Authors: Craciun Alexandru , Grigore Oana-Valeria
Published: May 2022

An optical system comprising a c-cut uniaxial crystal positioned between two axicons and illuminated by a Gaussian or a Laguerre–Gauss mode was used to demonstrate the generation of various vector vortex beams. We focused the generated beams using a 1 m focal length lens and we investigated their intensity profile and the polarization state in the focal plane of the focusing element. We showed that the achieved intensity profile can be controlled by changing the polarization state of the beam incident on the crystal. We observed that, for a particular configuration of the system, the initial circular symmetry of the beam is no longer preserved. The experiments were performed with Ti:Sapphire lasers that were operated in continuous wave mode, as well as in pulsed regime. The optical system presented here ensures a convenient way to generate a great variety of vector vortex beams and it is expected to be of interest for applications that use low and high-power laser sources, such as STED microscopy, light trapping, or material processing.
Multiple long-range host shifts of major Wolbachia supergroups infecting arthropods
Authors: Gomes Tiago M. F. F. , Wallau Gabriel L. , Loreto Elgion L. S.
Published: May 2022

Wolbachiais a genus of intracellular bacterial endosymbionts found in 20–66% of all insect species and a range of other invertebrates. It is classified as a single species,Wolbachia pipientis, divided into supergroups A to U, with supergroups A and B infecting arthropods exclusively.Wolbachiais transmitted mainly via vertical transmission through female oocytes, but can also be transmitted across different taxa by host shift (HS): the direct transmission ofWolbachiacells between organisms without involving vertically transmitted gametic cells. To assess the HS contribution, we recovered 50 orthologous genes from over 1000Wolbachiagenomes, reconstructed their phylogeny and calculated gene similarity. Of 15 supergroup AWolbachialineages, 10 have similarities ranging from 95 to 99.9%, while their hosts’ similarities are around 60 to 80%. For supergroup B, four out of eight lineages, which infect diverse and distantly-related organisms such as Acari, Hemiptera and Diptera, showed similarities from 93 to 97%. These results show thatWolbachiagenomes have a much higher similarity when compared to their hosts’ genes, which is a major indicator of HS. Our comparative genomic analysis suggests that, at least for supergroups A and B, HS is more frequent than expected, occurring even between distantly-related species.
An immune gene signature to predict prognosis and immunotherapeutic response in lung adenocarcinoma
Authors: Chen Hongquan , Lin Renxi , Lin Weibin , Chen Qing , Ye Dongjie , Li Jing , Feng Jinan , Cheng Wenxiu , Zhang Mingfang , Qi Yuanlin
Published: May 2022

Lung adenocarcinoma is one of the most common malignant tumors worldwide. The purpose of this study was to construct a stable immune gene signature for prediction of prognosis (IGSPP) and response to immune checkpoint inhibitors (ICIs) therapy in LUAD patients. Five genes were screened by weighted gene coexpression network analysis, Cox regression and LASSO regression analyses and were used to construct the IGSPP. The survival rate of the IGSPP low-risk group was higher than that of the IGSPP high-risk group. Multivariate Cox regression analysis showed that IGSPP could be used as an independent prognostic factor for the overall survival of LUAD patients. IGSPP genes were enriched in cell cycle pathways. IGSPP gene mutation rates were higher in the high-risk group. CD4 memory-activated T cells, M0 and M1 macrophages had higher infiltration abundance in the high-risk group, which was associated with poor overall survival. In contrast, the abundance of resting CD4 memory T cells, monocytes, resting dendritic cells and resting mast cells associated with a better prognosis was higher in the low-risk group. TIDE scores and the expressions of different immune checkpoints showed that patients in the high-risk IGSPP group benefited more from ICIs treatment. In short, an IGSPP of LUAD was constructed and characterized. It could be used to predict the prognosis and benefits of ICIs treatment in LUAD patients.
The isolation and expression analysis of cinnamate 4-hydroxylase and chalcone synthase genes of Scrophularia striata under different abiotic elicitors
Authors: Rostami Zeinab , Fazeli Arash , Hojati Zohreh
Published: May 2022

The phenylpropanoid pathway serves as a rich source of metabolites in plants, and it is considered as a starting point for the production of many other important compounds such as the flavonoids, flavonols, coumarins, and lignans.Scrophularia striatais a member of the Lamiaceae family with some biological activities similar to flavonoid compounds such as antioxidant, antibacterial, anti-inflammatory and analgesic activities. Cinnamate 4-hydroxylase (C4H) and Chalcone synthase (CHS) are key enzymes of the phenylpropanoid pathway, leading to the biosynthesis of several secondary metabolites. In this study, twoS. striataCHS and C4H were isolated and then analyzed. The investigation of the expression of these genes was performed under the effects of three salicylic acid (SA), jasmonic acid (JA), and gibberellic acid (GA) at concentrations of 100 and 300 ppm with a completely randomized design at the transcript level using Real Time PCR method. These have different expression patterns at developmental stages. Moreover, these genes present different sensitivities to hormonal treatment. Considering the total results, it was found that the amount of expression of these genes during the reproductive phase is higher than that of the vegetative phase. Additionally, the treatment of 300 ppm SA in the reproductive phase is the most effective treatment on increasing the corresponding phenylpropanoid compounds. A correlation analysis was performed between the phenylpropanoid compounds content and both CHS and C4H expression values at different phenological development stages. The results indicate that the expression variations of both CHS and C4H are significantly related to the changes in total phenolic content. We believe that the isolation of CHS and C4H can be helpful in better understanding phenylpropanoid metabolis.
Odor perception and symptoms during acrolein exposure in individuals with and without building-related symptoms
Authors: Palmquist Eva , Claeson Anna-Sara
Published: May 2022

Building-related symptoms (BRS) is a significant work-related and public health problem, characterized by non-specific symptoms occurring in a particular building. The cause of BRS is unknown, but certain reactive compounds are suggested risk factors. The aim of this controlled exposure study was to investigate whether BRS cases report more odor annoyance and symptoms and show altered autonomous nervous system (ANS) response during exposure to the reactive aldehyde, acrolein in comparison with referents. Individuals with BRS (n = 18) and referents (n = 14) took part in two exposure sessions (80 min). One session contained heptane alone, and the other heptane and acrolein. Perceived odor annoyance; eye, nose, and throat symptoms; and ANS response were measured continuously. BRS cases did not experience more odor annoyance; eye, nose, and throat symptoms; or altered ANS response in comparison with referents during the exposures. Supplementary analyses revealed that BRS cases that also reported chemical intolerance perceived more symptoms than referents during acrolein exposure. Acrolein exposure at a concentration below previously reported sensory irritation detection thresholds is perceived as more irritating by a subgroup of BRS individuals compared with referents. The results of this study indicate that a subset of individuals with building related symptoms (BRS) has a lowered sensory irritation threshold towards acrolein exposure. Future guidelines on chemical exposures to acrolein should take time and individual sensitivity into account.
Clinico-epidemiology and management of hump-nosed pit viper (Hypnale spp.) bites in dogs
Authors: Adhikari Ranjith , Suriyagoda Lalith , Premarathna Amal D. , Tuvikene Rando , Mallawa Chandima , De Silva Niranjala , Dangolla Ashoka , Silva Indira , Gawarammana Indika
Published: May 2022

Human envenoming from the bite of the abundant hump-nosed pit viper (Hypnale spp.) (HNPV) is a frequent occurrence with victims experiencing unpleasant and sometimes life-threatening consequences. Further, clinico-pathology, treatment and management measures in HNPV envenomed dogs are under recognized. Prospective investigations were performed to assess the clinico-pathology and management options for HNPV envenomed dogs brought to the University of Peradeniya’s Veterinary Teaching Hospital from January, 2012 to March 2018. We recorded the local and systemic manifestations, hematological and urinary abnormalities of 78 dogs in which HNPV bite had been witnessed by the owner. Mild swelling, extensive swelling, hemorrhagic blistering and hemorrhagic bullae at the site of bite were observed in 59%, 31%, 6% and 4% of the dogs, respectively. Some dogs were subjected to surgical excision of necrotized tissue including limb amputation. We observed the following systemic clinical effects in envenomed dogs: neurotoxicity (13%), acute kidney injury (AKI) (14%) and coagulopathy (16%). All dogs showed leukocytosis with mean white blood cell count of 25.25 × 103/µL. Mild anemia and thrombocytopenia were detected in 29% of the dogs. There was a significant correlation between extent of local tissue injuries with length of hospitalization (LH). The mean time of coagulopathy observed was 21.3 h (IQR: 8–48 h). In coagulopathic dogs, there was a strong correlation between LH and extent of local tissue injury (rs = 0.7751, P < 0.0001); LH and whole blood clotting time(CT) (rs = 1.0, P < 0.0001); PT and aPTT (rs = 0.4712, P < 0.001). LH was significantly correlated with the development of AKI (p = 0.0013). Lack of specific antivenom (AVS) for HNPV envenoming provided an opportunity to study the remaining treatment options. Therefore, the study allowed the identification of local and systemic effects, hematological abnormalities, possible supportive treatments and drawbacks of management measures for envenomed dogs.
27-Hydroxycholesterol induces expression of zonula occludens-1 in monocytic cells via multiple kinases pathways
Authors: Cho Hyok-rae , Kim Bo-Young , Kim Koanhoi , Lee Dongjun , Eo Seong-Kug , Son Yonghae
Published: May 2022

Zonula occludens (ZO)-1, a tight-junction protein (TJP), is expressed in dendritic cells (DCs) but not in monocytes, and 27-hydroxycholesterol (27OHChol) drives the differentiation of monocytes into DCs. Because the effects of 27OHChol on ZO-1 are not yet clearly defined, we investigated whether 27OHChol induces expression of the TJP. The treatment of human THP-1 monocytic cells with 27OHChol resulted in the elevated transcript levels of ZO-1 but not of ZO-2 or -3. 27OHChol increased the total amount of ZO-1 protein in the cells as well as its level on the cells surface. Cholesterol, however, did not influence expression of ZO-1. And, the expression of ZO-1 protein was mediated by endoplasmic reticulum (ER)-to-Golgi body transport system. Pharmacological kinase inhibition with LY294002 (a PI3K inhibitor), U0126 (a MEK/ERK inhibitor), or PP2 (a Src family kinase inhibitor) resulted in impaired ZO-1 expression at both transcript and protein levels. Drugs that are reported to suppress DC differentiation also inhibited 27OHChol-mediated expression and the localization of ZO-1, indicating the coincidence of ZO-1 upregulation and DC differentiation. These results suggest that ZO-1 is differentially expressed while monocytes differentiate into DCs in the presence of 27OHChol via pathways in which distinct signaling molecules are involved.
Effect of the pressureless post-sintering on the hot isostatic pressed Al2O3 prepared from the oxidized AlN powder
Authors: Balázsi K. , Varanasi D. , Horváth Zs. E. , Furkó M. , Cinar F. S. , Balázsi C.
Published: May 2022

The effect of the pressureless post-sintering in hydrogen on the structural and mechanical properties of the hot isostatic pressed Al2O3 prepared by oxidized AlN powder has been studied. The micrometer size AlN powder has been oxidized in air at 900° C and sintered by hot isostatic pressing (HIP) at 1700 °C, 20 MPa nitrogen atmosphere for 5 h. Pressureless sintering (PS) has been applied for all HIP sintered samples in H2 gas at 1800° C for 10 h. It has been shown that the oxidation caused a core–shell AlN/Al2O3 structure and the amount of Al2O3 increased with increasing of the oxidation time of the AlN powder. For the first time, the green samples obtained from oxidized AlN powder have been successfully sintered first by HIP followed by post-sintering by PS under hydrogen without adding any sintering additives. All post-sintered samples exhibited the main α-Al2O3 phase. Sintering in H2 caused the full transformation of AlN to α-Al2O3 phase and their better densification. Therefore, the hardness values of post-sintered samples have been increased to 17–18 GPa having apparent densities between 3.11 and 3.39 g/cm3.