bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docking sites inside Cas9 for adenine base editing diversification and RNA off-target elimination
Authors: Li Shuo , Yuan Bo , Cao Jixin , Chen Jingqi , Chen Jinlong , Qiu Jiayi , Zhao Xing-Ming , Wang Xiaolin , Qiu Zilong , Cheng Tian-Lin 
Published: November 2020

AbstractBase editing tools with diversified editing scopes and minimized RNA off-target activities are required for broad applications. Nevertheless, current Streptococcus pyogenes Cas9 (SpCas9)-based adenine base editors (ABEs) with minimized RNA off-target activities display constrained editing scopes with efficient editing activities at positions 4-8. Here, functional ABE variants with diversified editing scopes and reduced RNA off-target activities are identified using domain insertion profiling inside SpCas9 and with different combinations of TadA variants. Engineered ABE variants in this study display narrowed, expanded or shifted editing scopes with efficient editing activities across protospacer positions 2-16. And when combined with deaminase engineering, the RNA off-target activities of engineered ABE variants are further minimized. Thus, domain insertion profiling provides a framework to improve and expand ABE toolkits, and its combination with other strategies for ABE engineering deserves comprehensive explorations in the future.
Understanding complex dynamics of behavioral, neurochemical and transcriptomic changes induced by prolonged chronic unpredictable stress in zebrafish
Authors: Demin Konstantin A. , Lakstygal Anton M. , Krotova Nataliya A. , Masharsky Alexey , Tagawa Natsuki , Chernysh Maria V. , Ilyin Nikita P. , Taranov Alexander S. , Galstyan David S. , Derzhavina Ksenia A. , Levchenko Nataliia A. , Kolesnikova Tatiana O. , Mor Mikael S. , Vasyutina Marina L. , Efimova Evgeniya V. , Katolikova Nataliia , Prjibelski Andrey D. , Gainetdinov Raul R. , de Abreu Murilo S. , Amstislavskaya Tamara G. , Strekalova Tatyana , Kalueff Allan V. 
Published: November 2020

AbstractStress-related neuropsychiatric disorders are widespread, debilitating and often treatment-resistant illnesses that represent an urgent unmet biomedical problem. Animal models of these disorders are widely used to study stress pathogenesis. A more recent and historically less utilized model organism, the zebrafish (Danio rerio), is a valuable tool in stress neuroscience research. Utilizing the 5-week chronic unpredictable stress (CUS) model, here we examined brain transcriptomic profiles and complex dynamic behavioral stress responses, as well as neurochemical alterations in adult zebrafish and their correction by chronic antidepressant, fluoxetine, treatment. Overall, CUS induced complex neurochemical and behavioral alterations in zebrafish, including stable anxiety-like behaviors and serotonin metabolism deficits. Chronic fluoxetine (0.1 mg/L for 11 days) rescued most of the observed behavioral and neurochemical responses. Finally, whole-genome brain transcriptomic analyses revealed altered expression of various CNS genes (partially rescued by chronic fluoxetine), including inflammation-, ubiquitin- and arrestin-related genes. Collectively, this supports zebrafish as a valuable translational tool to study stress-related pathogenesis, whose anxiety and serotonergic deficits parallel rodent and clinical studies, and genomic analyses implicate neuroinflammation, structural neuronal remodeling and arrestin/ubiquitin pathways in both stress pathogenesis and its potential therapy.
Epstein–Barr virus peptides derived from latent cycle proteins alter NKG2A + NK cell effector function
Authors: Mbiribindi Berenice , Pena Josselyn K. , Arvedson Matthew P. , Moreno Romero Claudia , McCarthy Sarah R. , Hatton Olivia L. , Esquivel Carlos O. , Martinez Olivia M. , Krams Sheri M. 
Published: November 2020

AbstractNatural killer (NK) cells control viral infection through the interaction between inhibitory receptors and human leukocyte antigen (HLA) ligands and bound peptide. NK cells expressing the inhibitory receptor NKG2A/CD94 recognize and respond to autologous B cells latently infected with Epstein–Barr virus (EBV). The mechanism is not yet understood, thus we investigated peptides derived from seven latent proteins of EBV in the interaction of NKG2A and its ligand HLA-E. Functional analysis demonstrated that EBV peptides can bind to HLA-E and block inhibition of NK cell effector function. Moreover, analysis of DNA from 79 subjects showed sequence variations in the latent protein, LMP1, which alters NK responses to EBV. We provide evidence that peptides derived from EBV latent cycle proteins can impair the recognition of NKG2A despite being presented by HLA-E, resulting in NK cell activation.
Biosynthesis of zinc oxide nanoparticles by cell-biomass and supernatant of Lactobacillus plantarum TA4 and its antibacterial and biocompatibility properties
Authors: Mohd Yusof Hidayat , Abdul Rahman Nor’Aini , Mohamad Rosfarizan , Zaidan Uswatun Hasanah , Samsudin Anjas Asmara 
Published: November 2020

AbstractThis study aims to utilize the cell-biomass (CB) and supernatant (CFS) of zinc-tolerant Lactobacillus plantarum TA4 as a prospective nanofactory to synthesize ZnO NPs. The surface plasmon resonance for the biosynthesized ZnO NPs-CFS and ZnO NPs-CB was 349 nm and 351 nm, respectively, thereby confirming the formation of ZnO NPs. The FTIR analysis revealed the presence of proteins, carboxyl, and hydroxyl groups on the surfaces of both the biosynthesized ZnO NPs that act as reducing and stabilizing agents. The DLS analysis revealed that the poly-dispersity indexes was less than 0.4 for both ZnO NPs. In addition, the HR-TEM micrographs of the biosynthesized ZnO NPs revealed a flower-like pattern for ZnO NPs-CFS and an irregular shape for ZnO NPs-CB with particles size of 291.1 and 191.8 nm, respectively. In this study, the biosynthesized ZnO NPs exhibited antibacterial activity against pathogenic bacteria in a concentration-dependent manner and showed biocompatibility with the Vero cell line at specific concentrations. Overall, CFS and CB of L. plantarum TA4 can potentially be used as a nanofactory for the biological synthesis of ZnO NPs.
Characterizing the function of EPB41L4A in the predisposition to papillary thyroid carcinoma
Authors: Comiskey Daniel F. , He Huiling , Liyanarachchi Sandya , Sheikh Mehek S. , Hendrickson Isabella V. , Yu Lianbo , Brock Pamela L. , de la Chapelle Albert 
Published: November 2020

AbstractPapillary thyroid carcinoma (PTC) is the most common histotype of thyroid carcinoma. The heritability of PTC is high compared to other cancers, but its underlying causes are unknown. A recent genome-wide association study revealed the association of a variant at the 5q22 locus, rs73227498, with PTC predisposition. We report that rs17134155, a variant in high linkage disequilibrium with rs73227498, is located in an enhancer region downstream of coding transcripts of EPB41L4A. Rs17134155 showed significant enhancer activity in luciferase assays, and haplotypes containing the protective allele of this variant conferred a significantly lower risk of PTC. While the index SNP, rs73227498, acted as a significant cis-eQTL for expression of EPB41L4A, rs17134155 was a significant cis-sQTL for the alternative splicing of a non-coding transcript of EPB41L4A, called EPB41L4A-203. We also performed knockdown of EPB41L4A followed by microarray analysis. Some of the top differentially-expressed genes were represented among regulators of the WNT/β-catenin signaling pathway. Our results indicate that an enhancer region at 5q22 regulates the expression and splicing of EPB41L4A transcripts. We also provide evidence that EPB41L4A expression is involved in regulating growth and differentiation pathways, suggesting that decreased expression of EPB41L4A is a mechanism in the predisposition to PTC.
Specific decreasing of Na+ channel expression on the lateral membrane of cardiomyocytes causes fatal arrhythmias in Brugada syndrome
Authors: Tsumoto Kunichika , Ashihara Takashi , Naito Narumi , Shimamoto Takao , Amano Akira , Kurata Yasutaka , Kurachi Yoshihisa 
Published: November 2020

AbstractReduced cardiac sodium (Na+) channel current (INa) resulting from the loss-of-function of Na+ channel is a major cause of lethal arrhythmias in Brugada syndrome (BrS). Inspired by previous experimental studies which showed that in heart diseases INa was reduced along with expression changes in Na+ channel within myocytes, we hypothesized that the local decrease in INa caused by the alteration in Na+ channel expression in myocytes leads to the occurrence of phase-2 reentry, the major triggering mechanism of lethal arrhythmias in BrS. We constructed in silico human ventricular myocardial strand and ring models, and examined whether the Na+ channel expression changes in each myocyte cause the phase-2 reentry in BrS. Reducing Na+ channel expression in the lateral membrane of each myocyte caused not only the notch-and-dome but also loss-of-dome type action potentials and slowed conduction, both of which are typically observed in BrS patients. Furthermore, the selective reduction in Na+ channels on the lateral membrane of each myocyte together with spatial tissue heterogeneity of Na+ channel expression caused the phase-2 reentry and phase-2 reentry-mediated reentrant arrhythmias. Our data suggest that the BrS phenotype is strongly influenced by expression abnormalities as well as genetic abnormalities of Na+ channels.
The northernmost haulout site of South American sea lions and fur seals in the western South Atlantic
Authors: Procksch Natália , Grandi M. Florencia , Ott Paulo Henrique , Groch Karina , Flores Paulo A. C. , Zagonel Marcelo , Crespo Enrique A. , Machado Rodrigo , Pavez Guido , Guimarães Murilo , Veronez Maurício , de Oliveira Larissa Rosa 
Published: November 2020

AbstractWe present estimates of the seasonal and spatial occupation by pinnipeds of the Wildlife Refuge of Ilha dos Lobos (WRIL), based on aerial photographic censuses. Twenty aerial photographic censuses were analysed between July 2010 and November 2018. To assess monthly differences in the numbers of pinnipeds in the WRIL we used a Generalized Linear Mixed Model. Spatial analysis was carried out using Kernel density analysis of the pinnipeds on a grid plotted along the WRIL. Subadult male South American sea lions (Otaria flavescens) were the most abundant pinniped in the WRIL. Potential females of this species were also recorded during half of the census. The maximum number of pinnipeds observed in the WRIL was 304 in September 2018, including an unexpected individual southern elephant seal (Mirounga leonina), and a high number of South American fur seal yearlings (Arctocephalus australis). However, there was no statistically significant difference in counts between months. In all months analysed, pinnipeds were most often found concentrated in the northern portion of the island, with the highest abundances reported in September. This study confirms the importance of the WRIL as a haulout site for pinnipeds in Brazil, recommends that land research and recreational activities occur in months when no pinnipeds are present, and encourages a regulated marine mammal-based tourism during winter and spring months.
Investigation of the crystallization process of CSD-ErBCO on IBAD-substrate via DSD approach
Authors: Hayasaka R. , Cayado P. , Erbe M. , Freitag W. , Hänisch J. , Holzapfel B. , Ito S. , Hashizume H. 
Published: November 2020

AbstractREBa2Cu3O7-δ (REBCO, RE: rare earth, such as Y and Gd) compounds have been extensively studied as a superconducting layer in coated conductors. Although ErBCO potentially has better superconducting properties than YBCO and GdBCO, little research has been made on it, especially in chemical solution deposition (CSD). In this work, ErBCO films were deposited on IBAD (ion-beam-assisted-deposition) substrates by CSD with low-fluorine solutions. The crystallization process was optimized to achieve the highest self-field critical current density (Jc) at 77 K. Commonly, for the investigation of a CSD process involving numerous process factors, one factor is changed keeping the others constant, requiring much time and cost. For more efficient investigation, this study adopted a novel design-of-experiment technique, definitive screening design (DSD), for the first time in CSD process. Two different types of solutions containing Er-propionate or Er-acetate were used to make two types of samples, Er-P and Er-A, respectively. Within the investigated range, we found that crystallization temperature, dew point, and oxygen partial pressure play a key role in Er-P, while the former two factors are significant for Er-A. DSD revealed these significant factors among six process factors with only 14 trials. Moreover, the DSD approach allowed us to create models that predict Jc accurately. These models revealed the optimum conditions giving the highest Jc values of 3.6 MA/cm2 for Er-P and 3.0 MA/cm2 for Er-A. These results indicate that DSD is an attractive approach to optimize CSD process.
Acute kidney injury risk in orthopaedic trauma patients pre and post surgery using a biomarker algorithm and clinical risk score
Authors: Kurth Mary Jo , McBride William T. , McLean Gavin , Watt Joanne , Domanska Anna , Lamont John V. , Maguire Daniel , Fitzgerald Peter , Ruddock Mark W. 
Published: November 2020

AbstractAcute kidney injury (AKI) after major trauma is associated with increased mortality. The aim of this study was to assess if measurement of blood biomarkers in combination with clinical characteristics could be used to develop a tool to assist clinicians in identifying which orthopaedic trauma patients are at risk of AKI. This is a prospective study of 237 orthopaedic trauma patients who were consecutively scheduled for open reduction and internal fixation of their fracture between May 2012 and August 2013. Clinical characteristics were recorded, and 28 biomarkers were analysed in patient blood samples. Post operatively a combination of H-FABP, sTNFR1 and MK had the highest predictive ability to identify patients at risk of developing AKI (AUROC 0.885). Three clinical characteristics; age, dementia and hypertension were identified in the orthopaedic trauma patients as potential risks for the development of AKI. Combining biomarker data with clinical characteristics allowed us to develop a proactive AKI clinical tool, which grouped patients into four risk categories that were associated with a clinical management regime that impacted patient care, management, length of hospital stay, and efficient use of hospital resources.
Follistatin expressed in mechanically-damaged salivary glands of male mice induces proliferation of CD49f+ cells
Authors: Ikeda A. , Yamamoto T. , Mineshiba J. , Takashiba S. 
Published: November 2020

AbstractSalivary glands (SGs) are very important for maintaining the physiological functions of the mouth. When SGs regenerate and repair from various damages, including mechanical, radiological, and immune diseases, acinar and granular duct cells originate from intercalated duct cells. However, the recovery is often insufficient because of SGs' limited self-repair function. Furthermore, the precise repair mechanism has been unclear. Here, we focused on CD49f, one of the putative stem cell markers, and characterized CD49f positive cells (CD49f+ cells) isolated from male murine SGs. CD49f+ cells possess self-renewal ability and express epithelial and pluripotent markers. Compared to CD49f negative cells, freshly isolated CD49f+ cells highly expressed inhibin beta A and beta B, which are components of activin that has anti-proliferative effects. Notably, an inhibitor of activin, follistatin was expressed in mechanically-damaged SGs, meanwhile no follistatin was expressed in normal SGs in vivo. Moreover, sub-cultured CD49f+ cells highly expressed both Follistatin and a series of proliferative genes, expressions of which were decreased by Follistatin siRNA. These findings indicated that the molecular interaction between activin and follistatin may induce CD49f+ cells proliferation in the regeneration and repair of mouse SGs.
Solution-processed, semitransparent organic photovoltaics integrated with solution-doped graphene electrodes
Authors: Chang Jan-Kai , Huang Yu-Yun , Lin Ding-Lun , Tau Jieh-I. , Chen Ting-Hao , Chen Mei-Hsin 
Published: November 2020

AbstractIn this work, by applying a transfer method simultaneously with a solution doping process for graphene as top electrodes, we demonstrate a solution-processed semitransparent organic photovoltaics (OPV). The work function of doped graphene under various doping conditions was investigated via photoemission spectroscopy. The transparent device was fabricated using PEDOT-doped graphene as electrodes, which provide an energetically favorable band alignment for carrier extractions. The solution-processed semitransparent organic photovoltaics exhibit the power conversion efficiency (PCE) of 4.2%, which is 85.7% of the PCE of control devices based on metallic reflecting electrodes, while maintaining good transparency at most visible wavelengths.
Peripheral oxytocin injection modulates vomeronasal sensory activity and reduces pup-directed aggression in male mice
Authors: Nakahara Thiago S. , Camargo Antonio P. , Magalhães Pedro H. M. , Souza Mateus A. A. , Ribeiro Pedro G. , Martins-Netto Paulo H. , Carvalho Vinicius M. A. , José Juliana , Papes Fabio 
Published: November 2020

AbstractBehaviors are shaped by hormones, which may act either by changing brain circuits or by modifying sensory detection of relevant cues. Pup-directed behaviors have been previously shown to change via action of hormones at the brain level. Here, we investigated hormonal control of pup-induced activity in the vomeronasal organ, an olfactory sensory structure involved in the detection of non-volatile chemosignals. Vomeronasal activity decreases as males switch from a pup-aggressive state to a non-aggressive parenting state, after they socially contact a female. RNA sequencing, qPCR, and in situ hybridization were used to identify expression, in the vomeronasal sensory epithelium, of candidate GPCR hormone receptors chosen by in silico analyses and educated guesses. After identifying that oxytocin and vasopressin receptors are expressed in the vomeronasal organ, we injected the corresponding hormones in mice and showed that oxytocin administration reduced both pup-induced vomeronasal activity and aggressive behavior. Conversely, injection of an oxytocin receptor antagonist in female-primed male animals, which normally exhibit reduced vomeronasal activity, significantly increased the number of active vomeronasal neurons. These data link oxytocin to the modulation of olfactory sensory activity, providing a possible mechanism for changes in male behavior after social experience with females.
Au–Ag alloy nanoparticle-incorporated AgBr plasmonic photocatalyst
Authors: Naya Shin-ichi , Tada Hiroaki 
Published: November 2020

AbstractA solid-phase photochemical method produces Au–Ag alloy nanoparticles (NPs) with a sharp size distribution and varying composition in AgBr crystals (Au–Ag@AgBr). These features render Au–Ag@AgBr promising as a material for the plasmonic photocatalyst further to provide a possibility of elucidating the action mechanism due to the optical tunability. This study shows that the visible-light activity of Au–Ag@AgBr for degradation of model water pollutant is very sensitive to the alloy composition with a maximum at the mole percent of Au to all Ag in AgBr (y) = 0.012 mol%. Clear positive correlation is observed between the photocatalytic activity and the quality factor defined as the ratio of the peak energy to the full width at half maximum of the localized surface plasmon resonance band. This finding indicates that Au–Ag@AgBr works as a local electromagnetic field enhancement-type plasmonic photocatalyst in which the Au–Ag NPs mainly promotes the charge separation. This conclusion was further supported by the kinetic analysis of the light intensity-dependence of external quantum yield.
Corticotropin-releasing factor infusion in the bed nucleus of the stria terminalis of lactating mice alters maternal care and induces behavioural phenotypes in offspring
Authors: Creutzberg Kerstin Camile , Kestering-Ferreira Érika , Viola Thiago Wendt , Wearick-Silva Luis Eduardo , Orso Rodrigo , Heberle Bernardo Aguzzoli , Albrechet-Souza Lucas , de Almeida Rosa Maria Martins , Grassi-Oliveira Rodrigo 
Published: November 2020

AbstractThe peripartum period is accompanied by numerous physiological and behavioural adaptations organised by the maternal brain. These changes are essential for adequate expression of maternal behaviour, thereby ensuring proper development of the offspring. The corticotropin-releasing factor (CRF) plays a key role in a variety of behaviours accompanying stress, anxiety, and depression. There is also evidence that CRF contributes to maladaptations during the peripartum period. We investigated the effects of CRF in the bed nucleus of the stria terminalis (BNST) of lactating mice during maternal care and analysed locomotor activity and anxiety-like behaviour in the offspring. The BNST has been implicated in anxiety behaviour and regulation of the stress response. The effects of intra-BNST CRF administration were compared with those induced by the limited bedding (LB) procedure, a model that produces altered maternal behaviour. BALB/cJ dams were exposed to five infusions of CRF or saline into the BNST in the first weeks after birth while the LB dams were exposed to limited nesting material from postnatal days (P) 2–9. Maternal behaviour was recorded in intercalated days, from P1-9. Offspring anxiety-like behaviour was assessed during adulthood using the open-field, elevated plus-maze, and light/dark tests. Both intra-BNST CRF and LB exposure produced altered maternal care, represented by decreased arched-back nursing and increased frequency of exits from the nest. These changes in maternal care resulted in robust sex-based differences in the offspring’s behavioural responses during adulthood. Females raised by CRF-infused dams exhibited increased anxiety-like behaviour, whereas males presented a significant decrease in anxiety. On the other hand, both males and females raised by dams exposed to LB showed higher locomotor activity. Our study demonstrates that maternal care is impaired by intra-BNST CRF administrations, and these maladaptations are similar to exposure to adverse early environments. These procedures, however, produce distinct phenotypes in mice during young adulthood and suggest sex-based differences in the susceptibility to poor maternal care.