bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deubiquitinase USP47-stabilized splicing factor IK regulates the splicing of ATM pre-mRNA
Authors: Ka Hye In , Lee Sunyi , Han Sora , Jeong Ae Lee , Park Ji Young , Joo Hyun Jeong , Soh Su Jung , Park Doyeon , Yang Young 
Published: May 2020

AbstractIK depletion leads to an aberrant mitotic entry because of chromosomal misalignment through the enhancement of Aurora B activity at the interphase. Here, we demonstrate that IK, a spliceosomal component, plays a crucial role in the proper splicing of the ATM pre-mRNA among other genes related with the DNA Damage Response (DDR). Intron 1 in the ATM pre-mRNA, having lengths <200 bp, was not spliced in the IK-depleted cells and led to a deficiency of the ATM protein. Subsequently, the IK depletion-induced ATM protein deficiency impaired the ability to repair the damaged DNA. Because the absence of SMU1 results in IK degradation, the mechanism underlying IK degradation was exploited. IK was ubiquitinated in the absence of SMU1 and then subjected to proteolysis through the 26S proteasome. To prevent the proteolytic degradation of IK, a deubiquitinating enzyme, USP47, directly interacted with IK and stabilized it through deubiquitination. Collectively, our results suggest that IK is required for proper splicing of the ATM pre-mRNA and USP47 contributes toward the stabilization of IK.
Immune cell profiling of COVID-19 patients in the recovery stage
by single-cell sequencing
Authors: Wen Wen , Su Wenru , Tang Hao , Le Wenqing , Zhang Xiaopeng , Zheng Yingfeng , Liu Xiuxing , Xie Lihui , Li Jianmin , Ye Jinguo , Dong Liwei , Cui Xiuliang , Miao Yushan , Wang Depeng , Dong Jiantao , Xiao Chuanle , Chen Wei , Wang Hongyang 
Published: May 2020

AbstractCOVID-19, caused by SARS-CoV-2, has recently affected over 1,200,000
people and killed more than 60,000. The key immune cell subsets change and their
states during the course of COVID-19 remain unclear. We sought to comprehensively
characterize the transcriptional changes in peripheral blood mononuclear cells
during the recovery stage of COVID-19 by single-cell RNA sequencing technique. It
was found that T cells decreased remarkably, whereas monocytes increased in patients
in the early recovery stage (ERS) of COVID-19. There was an increased ratio of
classical CD14++ monocytes with high inflammatory gene
expression as well as a greater abundance of
CD14++IL1β+ monocytes in
the ERS. CD4+ T cells and CD8+
T cells decreased significantly and expressed high levels of inflammatory genes in
the ERS. Among the B cells, the plasma cells increased remarkably, whereas the naïve
B cells decreased. Several novel B cell-receptor (BCR) changes were identified, such
as IGHV3-23 and IGHV3-7, and isotypes (IGHV3-15, IGHV3-30, and IGKV3-11) previously
used for virus vaccine development were confirmed. The strongest pairing
frequencies, IGHV3-23-IGHJ4, indicated a monoclonal state associated with SARS-CoV-2
specificity, which had not been reported yet. Furthermore, integrated analysis
predicted that IL-1β and M-CSF may be novel candidate target genes for inflammatory
storm and that TNFSF13, IL-18, IL-2, and IL-4 may be beneficial for the recovery of
COVID-19 patients. Our study provides the first evidence of an inflammatory immune
signature in the ERS, suggesting COVID-19 patients are still vulnerable after
hospital discharge. Identification of novel BCR signaling may lead to the
development of vaccines and antibodies for the treatment of COVID-19.
Transcriptional and epigenetic basis of Treg cell development and function: its genetic anomalies or variations in autoimmune diseases
Authors: Ohkura Naganari , Sakaguchi Shimon 
Published: May 2020

AbstractNaturally arising regulatory CD4+T (Treg) cells, which specifically express the transcription factor FoxP3 in the nucleus and CD25 and CTLA-4 on the cell surface, are a T-cell subpopulation specialized for immune suppression, playing a key role in maintaining immunological self-tolerance and homeostasis. FoxP3 is required for Treg function, especially for its suppressive activity. However, FoxP3 expression per se is not necessary for Treg cell lineage commitment in the thymus and insufficient for full Treg-type gene expression in mature Treg cells. It is Treg-specific epigenetic changes such as CpG demethylation and histone modification that can confer a stable and heritable pattern of Treg type gene expression on developing Treg cells in a FoxP3-independent manner. Anomalies in the formation of Treg-specific epigenome, in particular, Treg-specific super-enhancers, which largely include Treg-specific DNA demethylated regions, are indeed able to cause autoimmune diseases in rodents. Furthermore, in humans, single nucleotide polymorphisms in Treg-specific DNA demethylated regions associated with Treg signature genes, such asIL2RA (CD25)andCTLA4, can affect the development and function of naïve Treg cells rather than effector T cells. Such genetic variations are therefore causative of polygenic common autoimmune diseases including type 1 diabetes and rheumatoid arthritis via affecting endogenous natural Treg cells. These findings on the transcription factor network with FoxP3 at a key position as well as Treg-specific epigenetic landscape facilitate our understanding of Treg cell development and function, and can be exploited to prepare functionally stable FoxP3-expressing Treg cells from antigen-specific conventional T cells to treat autoimmune diseases.
TRAF3IP3 negatively regulates cytosolic RNA induced anti-viral signaling by promoting TBK1 K48 ubiquitination
Authors: Deng Meng , Tam Jason W. , Wang Lufei , Liang Kaixin , Li Sirui , Zhang Lu , Guo Haitao , Luo Xiaobo , Zhang Yang , Petrucelli Alex , Davis Beckley K. , Conti Brian J. , June Brickey W. , Ko Ching-Chang , Lei Yu L. , Sun Shaocong , Ting Jenny P. -Y. 
Published: May 2020

AbstractInnate immunity to nucleic acids forms the backbone for anti-viral immunity and several inflammatory diseases. Upon sensing cytosolic viral RNA, retinoic acid-inducible gene-I-like receptors (RLRs) interact with the mitochondrial antiviral signaling protein (MAVS) and activate TANK-binding kinase 1 (TBK1) to induce type I interferon (IFN-I). TRAF3-interacting protein 3 (TRAF3IP3, T3JAM) is essential for T and B cell development. It is also well-expressed by myeloid cells, where its role is unknown. Here we report that TRAF3IP3 suppresses cytosolic poly(I:C), 5’ppp-dsRNA, and vesicular stomatitis virus (VSV) triggers IFN-I expression in overexpression systems and Traf3ip3−/− primary myeloid cells. The mechanism of action is through the interaction of TRAF3IP3 with endogenous TRAF3 and TBK1. This leads to the degradative K48 ubiquitination of TBK1 via its K372 residue in a DTX4-dependent fashion. Mice with myeloid-specific gene deletion of Traf3ip3 have increased RNA virus-triggered IFN-I production and reduced susceptibility to virus. These results identify a function of TRAF3IP3 in the regulation of the host response to cytosolic viral RNA in myeloid cells.
A microsporidian impairs Plasmodium falciparum transmission in Anopheles arabiensis mosquitoes
Authors: Herren Jeremy K. , Mbaisi Lilian , Mararo Enock , Makhulu Edward E. , Mobegi Victor A. , Butungi Hellen , Mancini Maria Vittoria , Oundo Joseph W. , Teal Evan T. , Pinaud Silvain , Lawniczak Mara K. N. , Jabara Jordan , Nattoh Godfrey , Sinkins Steven P. 
Published: May 2020

AbstractA possible malaria control approach involves the dissemination in mosquitoes of inherited symbiotic microbes to block Plasmodium transmission. However, in the Anopheles gambiae complex, the primary African vectors of malaria, there are limited reports of inherited symbionts that impair transmission. We show that a vertically transmitted microsporidian symbiont (Microsporidia MB) in the An. gambiae complex can impair Plasmodium transmission. Microsporidia MB is present at moderate prevalence in geographically dispersed populations of An. arabiensis in Kenya, localized to the mosquito midgut and ovaries, and is not associated with significant reductions in adult host fecundity or survival. Field-collected Microsporidia MB infected An. arabiensis tested negative for P. falciparum gametocytes and, on experimental infection with P. falciparum, sporozoites aren’t detected in Microsporidia MB infected mosquitoes. As a microbe that impairs Plasmodium transmission that is non-virulent and vertically transmitted, Microsporidia MB could be investigated as a strategy to limit malaria transmission.
Non-vector-borne transmission of lumpy skin disease virus
Authors: Aleksandr Kononov , Olga Byadovskaya , David Wallace B. , Pavel Prutnikov , Yana Pestova , Svetlana Kononova , Alexander Nesterov , Vladimir Rusaleev , Dmitriy Lozovoy , Alexander Sprygin 
Published: May 2020

AbstractThe transmission of “lumpy skin disease virus” (LSDV) has prompted intensive research efforts due to the rapid spread and high impact of the disease in recent years, especially in Eastern Europe and Balkan countries. In this study, we experimentally evaluate the vaccine-derived virulent recombinant LSDV strain (Saratov/2017) and provide solid evidence on the capacity of the virus for transmission in a vector-proof environment. In the 60-day long experiment, we used inoculated bulls (IN group) and two groups of in-contact animals (C1 and C2), with the former (C1) being in contact with the inoculated animals at the onset of the trial and the latter (C2) being introduced at day 33 of the experiment. The infection in both groups of contact animals was confirmed clinically, serologically and virologically, and viremia was demonstrated in blood, nasal and ocular excretions, using molecular tools. Further studies into LSDV biology are a priority to gain insights into whether the hypothesized indirect contact mode evidenced in this study is a de novo-created feature, absent from both parental stains of the novel (recombinant) LSDV isolate used, or whether it was dormant, but then unlocked by the process of genetic recombination. Author summary: In global terms, LSD has been termed a “neglected disease” due to its historic natural occurrence of being restricted to Africa and, occasionally, Israel. However, after its slow spread throughout the Middle East, the disease is now experiencing a resurgence of research interest following a recent and rapid spread into more northern latitudes. Given the dearth of solid findings on potential transmission mechanisms, no efficient or reliable control program currently exists, which does not involve the use of live attenuated vaccines or stamping out policies – both of which are controversial for implementation in non-endemic regions or countries. The vector-borne mode is the only working concept currently available, but with scarce evidence to support the aggressive spread northwards – except for human-assisted spread, including legal or illegal animal transportation. The emergence of outbreaks is not consistently linked to weather conditions, with the potential for new outbreaks to occur and spread rapidly. Here, for the first time, we provide evidence for indirect contact-mode transmission for a naturally-occurring recombinant LSDV isolated from the field. In an insect-proof facility, we obtained solid evidence that the novel LSDV strain can pass to in-contact animals. Given the recombinant nature of the virus utilised, its genetic background relating to the observed transmission pattern within the study needs to be delineated.
Transcriptomic profiles reveal differences in zinc metabolism, inflammation, and tight junction proteins in duodenum from cholesterol gallstone subjects
Authors: Riveras Eleodoro , Azocar Lorena , Moyano Tomas C. , Ocares Marcia , Molina Hector , Romero Diego , Roa Juan C. , Valbuena Jose R. , Gutiérrez Rodrigo A. , Miquel Juan F. 
Published: May 2020

AbstractCholesterol Gallstone Disease (GSD) is a common multifactorial disorder characterized by crystallization and aggregation of biliary cholesterol in the gallbladder. The global prevalence of GSD is ~10–20% in the adult population but rises to 28% in Chile (17% among men and 30% among women). The small intestine may play a role in GSD pathogenesis, but the molecular mechanisms have not been clarified. Our aim was to identify the role of the small intestine in GSD pathogenesis. Duodenal biopsy samples were obtained from patients with GSD and healthy volunteers. GSD status was defined by abdominal ultrasonography. We performed a transcriptome study in a discovery cohort using Illumina HiSeq. 2500, and qPCR, immunohistochemistry and immunofluorescence were used to validate differentially expressed genes among additional case-control cohorts. 548 differentially expressed genes between GSD and control subjects were identified. Enriched biological processes related to cellular response to zinc, and immune and antimicrobial responses were observed in GSD patients. We validated lower transcript levels of metallothionein, NPC1L1 and tight junction genes and higher transcript levels of genes involved in immune and antimicrobial pathways in GSD patients. Interestingly, serum zinc and phytosterol to cholesterol precursor ratios were lower in GSD patients. A significant association was observed between serum zinc and phytosterol levels. Our results support a model where proximal small intestine plays a key role in GSD pathogenesis. Zinc supplementation, modulation of proximal microbiota and/or intestinal barrier may be novel targets for strategies to prevent GSD.
Clinical Performance of Flash Glucose Monitoring System in Patients with Liver Cirrhosis and Diabetes Mellitus
Authors: Costa Dalila , Lourenço Joana , Monteiro Ana Margarida , Castro Beatriz , Oliveira Patricia , Tinoco Maria Carmo , Fernandes Vera , Marques Olinda , Gonçalves Raquel , Rolanda Carla 
Published: May 2020

AbstractFlash glucose monitoring system (FGMS) is an improved subset of continuous glucose monitoring with a recognized effectiveness on glycemic control, though validation in patients with Liver Cirrhosis (LC) is lacking. To evaluate the accuracy of FGMS in patients with Type 2 Diabetes Mellitus (DM) and LC, a prospective, case-control study was performed in 61 ambulatory patients with LC and DM (LC group, n = 31) or DM (Control group, n = 30). During 14 days, patients performed 4 assessments per day of self-monitoring of blood glucose (SMBG, reference value) followed by FGMS scanning. There were 2567 paired SMBG and FGMS values used in the accuracy analysis, with an overall mean absolute relative difference (MARD) of 12.68% in the LC group and 10.55% in the control group (p < 0,001). In patients with LC, the percentage of readings within Consensus Consensus Error Grid analysis Zone A and A + B were 80.36% and 99,26%, respectively. Sensor clinical accuracy was not affected by factors such as body mass index, age, gender, Child-Pugh score or edematoascitic decompensation. This is the first study to approach FGMS clinical accuracy in LC, revealing a potential usability of this system to monitor glycemic control in this population.
A promising and cost-effective biochar adsorbent derived from jujube pit for the removal of Pb(II) from aqueous solution
Authors: Gao Junkai , Liu Yu , Li Xuebin , Yang Mouyuan , Wang Jinbao , Chen Yan 
Published: May 2020

AbstractThis study evaluated the Pb(II) sorption capacity of jujube pit biochar (JPB) in aqueous solution, which was derived from jujube pit by pyrolysis and used as a promising and economical adsorbent. More importantly, the utilization of JPB could realize the recycling of agricultural residues. The JPB was characterized using conventional science technologies, including SEM, BET and FT-IR, and the sorption capacity of JPB for lead ions was investigated according to different adsorption parameters, such as the kinetics data, solution pH, isotherms data, coexisting ions of Na+ and K+, desorption and reusability, and solution temperature. The results of kinetics data suggested that the lead ion adsorption process by JPB could be fast to reach equilibrium within 30 min. Additionally, the adsorption capacity of JPB for Pb(II) was calculated to be maximum for 137.1 mg/g at pH 6.0. More importantly, after five cycles of desorption and reuse, the JPB still reached 70% of its original adsorption capacity. All the results suggested that JPB had a broad application prospect for the purification of lead ions in practical.
Cell viscoelasticity is linked to fluctuations in cell biomass distributions
Authors: Nguyen Thang L. , Polanco Edward R. , Patananan Alexander N. , Zangle Thomas A. , Teitell Michael A. 
Published: May 2020

AbstractThe viscoelastic properties of mammalian cells can vary with biological state, such as during the epithelial-to-mesenchymal (EMT) transition in cancer, and therefore may serve as a useful physical biomarker. To characterize stiffness, conventional techniques use cell contact or invasive probes and as a result are low throughput, labor intensive, and limited by probe placement. Here, we show that measurements of biomass fluctuations in cells using quantitative phase imaging (QPI) provides a probe-free, contact-free method for quantifying changes in cell viscoelasticity. In particular, QPI measurements reveal a characteristic underdamped response of changes in cell biomass distributions versus time. The effective stiffness and viscosity values extracted from these oscillations in cell biomass distributions correlate with effective cell stiffness and viscosity measured by atomic force microscopy (AFM). This result is consistent for multiple cell lines with varying degrees of cytoskeleton disruption and during the EMT. Overall, our study demonstrates that QPI can reproducibly quantify cell viscoelasticity.
Al-, Ga-, Mg-, or Li-doped zinc oxide nanoparticles as electron transport layers for quantum dot light-emitting diodes
Authors: Alexandrov Alexei , Zvaigzne Mariya , Lypenko Dmitri , Nabiev Igor , Samokhvalov Pavel 
Published: May 2020

AbstractColloidal quantum dots and other semiconductor nanocrystals are essential components of next-generation lighting and display devices. Due to their easily tunable and narrow emission band and near-unity fluorescence quantum yield, they allow cost-efficient fabrication of bright, pure-color and wide-gamut light emitting diodes (LEDs) and displays. A critical improvement in the quantum dot LED (QLED) technology was achieved when zinc oxide nanoparticles (NPs) were first introduced as an electron transport layer (ETL) material, which tremendously enhanced the device brightness and current efficiency due to the high mobility of electrons in ZnO and favorable alignment of its energy bands. During the next decade, the strategy of ZnO NP doping allowed the fabrication of QLEDs with a brightness of about 200 000 cd/m2and current efficiency over 60 cd/A. On the other hand, the known ZnO doping approaches rely on a very fine tuning of the energy levels of the ZnO NP conduction band minimum; hence, selection of the appropriate dopant that would ensure the best device characteristics is often ambiguous. Here we address this problem via detailed comparison of QLEDs whose ETLs are formed by a set of ZnO NPs doped with Al, Ga, Mg, or Li. Although magnesium-doped ZnO NPs are the most common ETL material used in recently designed QLEDs, our experiments have shown that their aluminum-doped counterparts ensure better device performance in terms of brightness, current efficiency and turn-on voltage. These findings allow us to suggest ZnO NPs doped with Al as the best ETL material to be used in future QLEDs.
MicroRNA Profiling of Highly Enriched Human Corneal Epithelial Stem Cells by Small RNA Sequencing
Authors: Kalaimani Lavanya , Devarajan Bharanidharan , Subramanian Umadevi , Ayyasamy Vanniarajan , Namperumalsamy Venkatesh Prajna , Veerappan Muthukkaruppan , Chidambaranathan Gowri Priya 
Published: May 2020

AbstractThe objective of the study was to elucidate the microRNA (miRNA) profile of an enriched human corneal epithelial stem cell (CESC) population in comparison to differentiated central corneal epithelial cells (CCECs) by small RNA sequencing. The CESCs were enriched by differential enzymatic treatment to isolate the basal limbal epithelial cells followed by laser capture microdissection of cells with nucleus to cytoplasm ratio ≥0.7, from donor tissues. Small RNA sequencing was carried out using Illumina NextSeq. 500 platform and the validation of differentially expressed miRNAs by quantitative real-time PCR (qPCR) and locked nucleic acid miRNA in-situ hybridization (LNA-ISH). The sequencing identified 62 miRNAs in CESCs and 611 in CCECs. Six miRNAs: hsa-miR-21-5p, 3168, 143-3p, 10a-5p, 150-5p and 1910-5p were found to be significantly upregulated in enriched CESCs, which was further confirmed by qPCR and LNA-ISH. The expression of hsa-miR-143-3p was exclusive to clusters of limbal basal epithelial cells. The targets of the upregulated miRNAs were predicted to be associated with signaling pathways -Wnt, PI3K-AKT, MAPK and pathways that regulate pluripotency of stem cells, cell migration, growth and proliferation. Further studies are essential to elucidate their functional role in maintenance of stemness. The findings of the study also hypothesize the inherent potential of hsa-miR-143-3p to serve as a biomarker for identifying CESCs.
Region-specific effects of Scrapper on the abundance of glutamate and gamma-aminobutyric acid in the mouse brain
Authors: Eto Fumihiro , Sato Shumpei , Setou Mitsutoshi , Yao Ikuko 
Published: May 2020

AbstractThe brain consists of various areas with anatomical features. Neurons communicate with one another via excitatory or inhibitory synaptic transmission. Altered abundance of neurotransmitters, including glutamate and gamma-aminobutyric acid (GABA), in specific brain regions is closely involved in severe neurological diseases, such as schizophrenia and obsessive-compulsive disorder. SCRAPPER, a ubiquitin E3 ligase, regulates synaptic transmission. Scrapper gene deficiency results in defective neurotransmission due to excessive secretion of neurotransmitters. The present study employed matrix-assisted laser desorption/ionization imaging mass spectrometry to analyze the abundance of amino acid neurotransmitters in Scrapper knockout (SCR-KO) mice. SCR-KO mice exhibited significantly increased glutamate levels in the isocortex (CTX), corpus callosum (CC), thalamus (TH), midbrain (MB), cerebellar cortex (CBX), and caudoputamen (CP) and increased GABA levels in the CTX, CC, TH, MB, CBX and hypothalamus (HY) compared with wild-type mice. These findings indicate that Scrapper deficiency leads to upregulated glutamate and GABA levels in multiple regions. Our results show a differential, region-specific effect of Scrapper on the abundance of glutamate and GABA.
Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion
Authors: Frausto Ricardo F. , Swamy Vinay S. , Peh Gary S. L. , Boere Payton M. , Hanser E. Maryam , Chung Doug. D. , George Benjamin L. , Morselli Marco , Kao Liyo , Azimov Rustam , Wu Jessica , Pellegrini Matteo , Kurtz Ira , Mehta Jodhbir S. , Aldave Anthony J. 
Published: May 2020

AbstractThe advent of cell culture-based methods for the establishment and expansion of human corneal endothelial cells (CEnC) has provided a source of transplantable corneal endothelium, with a significant potential to challenge the one donor-one recipient paradigm. However, concerns over cell identity remain, and a comprehensive characterization of the cultured CEnC across serial passages has not been performed. To this end, we compared two established CEnC culture methods by assessing the transcriptomic changes that occur during in vitro expansion. In confluent monolayers, low mitogenic culture conditions preserved corneal endothelial cell state identity better than culture in high mitogenic conditions. Expansion by continuous passaging induced replicative cell senescence. Transcriptomic analysis of the senescent phenotype identified a cell senescence signature distinct for CEnC. We identified activation of both classic and new cell signaling pathways that may be targeted to prevent senescence, a significant barrier to realizing the potential clinical utility of in vitro expansion.