bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral blood lymphocyte proviral DNA predicts neurocognitive impairment in clade C HIV
Authors: Ruhanya Vurayai , Jacobs Graeme Brendon , Nyandoro George , Paul Robert H. , Joska John A. , Seedat Soraya , Glashoff Richard Helmuth , Engelbrecht Susan 
Published: July 2020

AbstractIt is not known if proviral DNA in the periphery corresponds to cognitive status in clade C as it does in clade B and recombinant forms. A cross-sectional study was conducted on participants investigated for HIV-associated neurocognitive impairment in South Africa. HIV-1 proviral DNA was quantified using a PCR assay targeting a highly conserved HIV-1 LTR-gag region. Fifty-four (36.7%) participants were cognitively impaired and 93 (63.3%) were not impaired. Forty-three (79.6%) of the cognitively impaired participants were female and 11 (20.4%) were male. There was no significant age difference between cognitively impaired and unimpaired participants (p = 0.42). HIV-1 DNA in cognitively impaired PLWH was significantly higher than in cognitively normal individuals (p = .016). Considering impaired participants, lymphocyte HIV-1 DNA was significantly higher in males than females (p = 0.02). There was a modest positive correlation between lymphocyte HIV-1 DNA and global deficit scores (GDS) r = 0.176; p = 0.03). The two measures of viral load, lymphocyte HIV-1 DNA copies/million and plasma RNA copies/ml, were positively correlated (r = 0.39; p < .001). After adjusting for other covariates, age, sex, treatment status, and the interactions between impairment and treatment, the multivariate regression showed association between proviral load and neurocognitive impairment; omega effect size was 0.04, p value = 0.010. The burden of HIV-1 peripheral blood lymphocyte proviral DNA corresponds to neurocognitive impairment among individuals infected with clade C disease. Therefore, therapeutic strategies to reduce the HIV-1 proviral DNA reservoir in lymphocytes may improve neurocognitive outcomes in PLWH.
Similarities and Differences in Cellular Processing of Biologically Relevant Nanoparticles
Authors: Kepsutlu Burcu , McNally James 
Published: July 2020

AbstractNanoparticles are endocytosed and trafficked within cells by selecting one or more of the cell's intrinsic processing pathways. However, general rules which drive this selection have not yet been defined. Therefore, each nanoparticle has to be investigated separately to determine its endocytosis and intracellular trafficking pathways. By using cryo SXT to investigate the cellular interaction of two different nanoparticles, we have uncovered some general rules about nanoparticle interactions with cells. Our results highlight not only the importance of cryo-SXT for nanoparticle investigation in the medical field, but also demonstrate that a well-controlled analysis makes it possible to discern general rules about cell-nanoparticle interactions.
Multifocal photoacoustic microscopy using a single-element ultrasonic transducer through an ergodic relay
Authors: Li Yang , Wong Terence T. W. , Shi Junhui , Hsu Hsun-Chia , Wang Lihong V. 
Published: July 2020

AbstractOptical-resolution photoacoustic microscopy (OR-PAM) has demonstrated high-spatial-resolution imaging of optical absorption in biological tissue. To date, most OR-PAM systems rely on mechanical scanning with confocally aligned optical excitation and ultrasonic detection, limiting the wide-field imaging speed of these systems. Although several multifocal OR-PA (MFOR-PA) systems have attempted to address this limitation, they are hindered by the complex design in a constrained physical space. Here, we present a two-dimensional (2D) MFOR-PAM system that utilizes a 2D microlens array and an acoustic ergodic relay. Using a single-element ultrasonic transducer, this system can detect PA signals generated from 400 optical foci in parallel and then raster scan the optical foci patterns to form an MFOR-PAM image. This system improves the imaging resolution of an acoustic ergodic relay system from 220 to 13 μm and enables 400-folds shorter scanning time than that of a conventional OR-PAM system at the same resolution and laser repetition rate. We demonstrated the imaging ability of the system with both in vitro and in vivo experiments.
Post-transplant multimorbidity index and quality of life in patients with chronic graft-versus-host disease—results from a joint evaluation of a prospective German multicenter validation trial and a cohort from the National Institutes of Health
Authors: Wolff Daniel , Herzberg Philipp Y. , Herrmann Anne , Pavletic Steven Z. , Heussner Pia , Mumm Friederike , Höfer Christina , Hilgendorf Inken , Hemmati Philipp G. , Holler Ernst , Greinix Hildegard , Mitchell Sandra A. 
Published: July 2020

AbstractComorbidity after allogeneic hematopoietic stem cell transplantation (alloHSCT) impairs quality of life (QoL), physical functioning, and survival. We developed a new standardized measure to capture comorbidity after transplantation, the Post-transplant Multimorbidity Index (PTMI) in a cohort of 50 long term survivors. We subsequently evaluated the content validity and impact on survival and QoL within a multicenter trial, including 208 patients (pts) after alloHSCT, who were prospectively evaluated applying the FACT-BMT, the Human Activity Profile (HAP), the SF-36 v.2, PTMI and the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI). The most prevalent comorbidities were compensated arterial hypertension (28.4%), ambulatory infections (25.5%), iron overload (23%), mild renal function impairment (20%), and osteoporosis (13%). Applying the PTMI 13% of patients had no comorbidity, while 37.1% had 1–3 comorbidities, 27.4% had 4–6 comorbidities, and 13.5% had > 6 comorbidities. Chronic graft-versus-host disease (cGvHD) was significantly associated with the PTMI, while age and prior acute GvHD were not. In contrast, the HCT-CI was not associated with the presence of cGvHD. cGvHD was significantly associated with depression (r = 0.16), neurological disease (r = 0.21), osteoporosis (r = 0.18) and nonmelanoma skin cancer (r = 0.26). The PTMI demonstrated strong measurement properties and compared to the HCT-CI captured a wider range of comorbidities associated with cGvHD.
RIP3-mediated necroptosis is regulated by inter-filament assembly of RIP homotypic interaction motif
Authors: Hu Hong , Wu Xialian , Wu Guoxiang , Nan Ning , Zhang Jing , Zhu Xinxin , Zhang Yu , Shu Zhaoqian , Liu Jia , Liu Xiaoyan , Lu Junxia , Wang Huayi 
Published: July 2020

AbstractNecroptosis is mediated by signaling complexes called necrosomes, which contain receptor-interacting protein 3 (RIP3) and upstream effectors, such as RIP1. In necrosomes, the RIP homotypic interaction motif (RHIM) of RIP3 and RIP1 forms amyloidal complex. But how the amyloidal necrosomes control RIP3 activation and cell necroptosis has not been determined. Here, we showed that RIP3 amyloid fibrils could further assemble into large fibrillar networks which presents as cellular puncta during necroptosis. A viral RHIM-containing necroptosis inhibitor M45 could form heteroamyloid with RIP3 in cells and prevent RIP3 puncta formation and cell necroptosis. We characterized mutual antagonism between RIP3–RHIM and M45–RHIM in necroptosis regulation, which was caused by distinct inter-filament interactions in RIP3, M45 amyloids revealed with atomic force microscopy. Moreover, double mutations Asn464 and Met468 in RIP3–RHIM to Asp disrupted RIP3 kinase-dependent necroptosis. While the mutant RIP3(N464D/M468D) could form amyloid as wild type upon necroptosis induction. Based on these results, we propose that RIP3 amyloid formation is required but not sufficient in necroptosis signaling, the ordered inter-filament assembly of RIP3 is critical in RIP3 amyloid mediated kinase activation and cell necroptosis.
Pyroptotic cell death in the R6/2 mouse model of Huntington’s disease: new insight on the inflammasome
Authors: Paldino Emanuela , D’Angelo Vincenza , Sancesario Giuseppe , Fusco Francesca R. 
Published: July 2020

AbstractMechanisms of tissue damage in Huntington’s disease involve excitotoxicity, mitochondrial damage, and neuroinflammation, including microglia activation. In the present study, we investigate the role of pyroptosis process in the striatal neurons of the R6/2 mouse model of Huntington’s disease. Transgenic mice were sacrificed at 4 and 13 weeks of age. After sacrifice, histological and immunohistochemical studies were performed. We found that NLRP3 and Caspase-1 were intensely expressed in 13-week-old R6/2 mice. Moreover, NLRP3 expression levels were higher in striatal spiny projection neurons and in parvalbumin interneurons, which are prone to degenerate in HD.
Demographic and prosocial intrapersonal characteristics of biobank participants and refusers: the findings of a survey in the Netherlands
Authors: Broekstra Reinder , Aris-Meijer Judith , Maeckelberghe Els , Stolk Ronald , Otten Sabine 
Published: July 2020

AbstractResearch in genetics relies heavily on voluntary contributions of personal data. We aimed to acquire insights into the differences between participants and refusers of participation in a Dutch population-based biobank. Accordingly, we assessed the demographic and prosocial intrapersonal characteristics of respondents who participated (n = 2615) or refused to participate (n = 404) in the Lifelines biobank and databank. Our results indicated that health-related values critically influence participation decisions. The participation threshold for Lifelines was determined by an absence of health-related values and of trust in government. Therefore, considering these factors in communication and recruitment strategies could enhance participation in biomedical research. No indications were found of a stronger general prosociality of participants or their trust in researchers beyond the context of biobanking. This emphasizes the contextual understanding of the decision of participation in biobanking. Our findings may contribute to improving recruitment strategies by incorporating relevant values and/or highlighting prosocial benefits. Moreover, they foreground the need to address trust issues in collaborations between data repositories and commercial companies. Future research should explore how prosocial intrapersonal characteristics drive participation and withdrawal decisions and relate to contextual attributes.
Retromer stabilization results in neuroprotection in a model of Amyotrophic Lateral Sclerosis
Authors: Muzio Luca , Sirtori Riccardo , Gornati Davide , Eleuteri Simona , Fossaghi Andrea , Brancaccio Diego , Manzoni Leonardo , Ottoboni Linda , Feo Luca De , Quattrini Angelo , Mastrangelo Eloise , Sorrentino Luca , Scalone Emanuele , Comi Giancarlo , Marinelli Luciana , Riva Nilo , Milani Mario , Seneci Pierfausto , Martino Gianvito 
Published: July 2020

AbstractAmyotrophic Lateral Sclerosis (ALS) is a fatal disease characterized by the degeneration of upper and lower motor neurons (MNs). We find a significant reduction of the retromer complex subunit VPS35 in iPSCs-derived MNs from ALS patients, in MNs from ALS post mortem explants and in MNs from SOD1G93A mice. Being the retromer involved in trafficking of hydrolases, a pathological hallmark in ALS, we design, synthesize and characterize an array of retromer stabilizers based on bis-guanylhydrazones connected by a 1,3-phenyl ring linker. We select compound 2a as a potent and bioavailable interactor of VPS35-VPS29. Indeed, while increasing retromer stability in ALS mice, compound 2a attenuates locomotion impairment and increases MNs survival. Moreover, compound 2a increases VPS35 in iPSCs-derived MNs and shows brain bioavailability. Our results clearly suggest the retromer as a valuable druggable target in ALS.
Néel-type skyrmion in WTe2/Fe3GeTe2 van der Waals heterostructure
Authors: Wu Yingying , Zhang Senfu , Zhang Junwei , Wang Wei , Zhu Yang Lin , Hu Jin , Yin Gen , Wong Kin , Fang Chi , Wan Caihua , Han Xiufeng , Shao Qiming , Taniguchi Takashi , Watanabe Kenji , Zang Jiadong , Mao Zhiqiang , Zhang Xixiang , Wang Kang L. 
Published: July 2020

AbstractThe promise of high-density and low-energy-consumption devices motivates the search for layered structures that stabilize chiral spin textures such as topologically protected skyrmions. At the same time, recently discovered long-range intrinsic magnetic orders in the two-dimensional van der Waals materials provide a new platform for the discovery of novel physics and effects. Here we demonstrate the Dzyaloshinskii–Moriya interaction and Néel-type skyrmions are induced at the WTe2/Fe3GeTe2 interface. Transport measurements show the topological Hall effect in this heterostructure for temperatures below 100 K. Furthermore, Lorentz transmission electron microscopy is used to directly image Néel-type skyrmion lattice and the stripe-like magnetic domain structures as well. The interfacial coupling induced Dzyaloshinskii–Moriya interaction is estimated to have a large energy of 1.0 mJ m−2. This work paves a path towards the skyrmionic devices based on van der Waals layered heterostructures.
Ceramic resonators for targeted clinical magnetic resonance imaging of the breast
Authors: Shchelokova Alena , Ivanov Viacheslav , Mikhailovskaya Anna , Kretov Egor , Sushkov Ivan , Serebryakova Svetlana , Nenasheva Elizaveta , Melchakova Irina , Belov Pavel , Slobozhanyuk Alexey , Andreychenko Anna 
Published: July 2020

AbstractCurrently, human magnetic resonance (MR) examinations are becoming highly specialized with a pre-defined and often relatively small target in the body. Conventionally, clinical MR equipment is designed to be universal that compromises its efficiency for small targets. Here, we present a concept for targeted clinical magnetic resonance imaging (MRI), which can be directly integrated into the existing clinical MR systems, and demonstrate its feasibility for breast imaging. The concept comprises spatial redistribution and passive focusing of the radiofrequency magnetic flux with the aid of an artificial resonator to maximize the efficiency of a conventional MR system for the area of interest. The approach offers the prospect of a targeted MRI and brings novel opportunities for high quality specialized MR examinations within any existing MR system.
Mapping allosteric communications within individual proteins
Authors: Wang Jian , Jain Abha , McDonald Leanna R. , Gambogi Craig , Lee Andrew L. , Dokholyan Nikolay V. 
Published: July 2020

AbstractAllostery in proteins influences various biological processes such as regulation of gene transcription and activities of enzymes and cell signaling. Computational approaches for analysis of allosteric coupling provide inexpensive opportunities to predict mutations and to design small-molecule agents to control protein function and cellular activity. We develop a computationally efficient network-based method, Ohm, to identify and characterize allosteric communication networks within proteins. Unlike previously developed simulation-based approaches, Ohm relies solely on the structure of the protein of interest. We use Ohm to map allosteric networks in a dataset composed of 20 proteins experimentally identified to be allosterically regulated. Further, the Ohm allostery prediction for the protein CheY correlates well with NMR CHESCA studies. Our webserver, Ohm.dokhlab.org, automatically determines allosteric network architecture and identifies critical coupled residues within this network.
The suboptimality of perceptual decision making with multiple alternatives
Authors: Yeon Jiwon , Rahnev Dobromir 
Published: July 2020

AbstractIt is becoming widely appreciated that human perceptual decision making is suboptimal but the nature and origins of this suboptimality remain poorly understood. Most past research has employed tasks with two stimulus categories, but such designs cannot fully capture the limitations inherent in naturalistic perceptual decisions where choices are rarely between only two alternatives. We conduct four experiments with tasks involving multiple alternatives and use computational modeling to determine the decision-level representation on which the perceptual decisions are based. The results from all four experiments point to the existence of robust suboptimality such that most of the information in the sensory representation is lost during the transformation to a decision-level representation. These results reveal severe limits in the quality of decision-level representations for multiple alternatives and have strong implications about perceptual decision making in naturalistic settings.
Exploiting natural chemical photosensitivity of anhydrotetracycline and tetracycline for dynamic and setpoint chemo-optogenetic control
Authors: Baumschlager Armin , Rullan Marc , Khammash Mustafa 
Published: July 2020

AbstractThe transcriptional inducer anhydrotetracycline (aTc) and the bacteriostatic antibiotic tetracycline (Tc) are commonly used in all fields of biology for control of transcription or translation. A drawback of these and other small molecule inducers is the difficulty of their removal from cell cultures, limiting their application for dynamic control. Here, we describe a simple method to overcome this limitation, and show that the natural photosensitivity of aTc/Tc can be exploited to turn them into highly predictable optogenetic transcriptional- and growth-regulators. This new optogenetic class uniquely features both dynamic and setpoint control which act via population-memory adjustable through opto-chemical modulation. We demonstrate this method by applying it for dynamic gene expression control and for enhancing the performance of an existing optogenetic system. We then expand the utility of the aTc system by constructing a new chemical bandpass filter that increases its aTc response range. The simplicity of our method enables scientists and biotechnologists to use their existing systems employing aTc/Tc for dynamic optogenetic experiments without genetic modification.
Stable high-capacity and high-rate silicon-based lithium battery anodes upon two-dimensional covalent encapsulation
Authors: Zhang Xinghao , Wang Denghui , Qiu Xiongying , Ma Yingjie , Kong Debin , Müllen Klaus , Li Xianglong , Zhi Linjie 
Published: July 2020

AbstractSilicon is a promising anode material for lithium-ion and post lithium-ion batteries but suffers from a large volume change upon lithiation and delithiation. The resulting instabilities of bulk and interfacial structures severely hamper performance and obstruct practical use. Stability improvements have been achieved, although at the expense of rate capability. Herein, a protocol is developed which we describe as two-dimensional covalent encapsulation. Two-dimensional, covalently bound silicon-carbon hybrids serve as proof-of-concept of a new material design. Their high reversibility, capacity and rate capability furnish a remarkable level of integrated performances when referred to weight, volume and area. Different from existing strategies, the two-dimensional covalent binding creates a robust and efficient contact between the silicon and electrically conductive media, enabling stable and fast electron, as well as ion, transport from and to silicon. As evidenced by interfacial morphology and chemical composition, this design profoundly changes the interface between silicon and the electrolyte, securing the as-created contact to persist upon cycling. Combined with a simple, facile and scalable manufacturing process, this study opens a new avenue to stabilize silicon without sacrificing other device parameters. The results hold great promise for both further rational improvement and mass production of advanced energy storage materials.
Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections
Authors: Sallah Neneh , Miley Wendell , Labo Nazzarena , Carstensen Tommy , Fatumo Segun , Gurdasani Deepti , Pollard Martin O. , Dilthey Alexander T. , Mentzer Alexander J. , Marshall Vickie , Cornejo Castro Elena M. , Pomilla Cristina , Young Elizabeth H. , Asiki Gershim , Hibberd Martin L. , Sandhu Manjinder , Kellam Paul , Newton Robert , Whitby Denise , Barroso Inês 
Published: July 2020

AbstractKaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr Virus (EBV) establish life-long infections and are associated with malignancies. Striking geographic variation in incidence and the fact that virus alone is insufficient to cause disease, suggests other co-factors are involved. Here we present epidemiological analysis and genome-wide association study (GWAS) in 4365 individuals from an African population cohort, to assess the influence of host genetic and non-genetic factors on virus antibody responses. EBV/KSHV co-infection (OR = 5.71(1.58–7.12)), HIV positivity (OR = 2.22(1.32–3.73)) and living in a more rural area (OR = 1.38(1.01–1.89)) are strongly associated with immunogenicity. GWAS reveals associations with KSHV antibody response in the HLA-B/C region (p = 6.64 × 10−09). For EBV, associations are identified for VCA (rs71542439, p = 1.15 × 10−12). Human leucocyte antigen (HLA) and trans-ancestry fine-mapping substantiate that distinct variants in HLA-DQA1 (p = 5.24 × 10−44) are driving associations for EBNA-1 in Africa. This study highlights complex interactions between KSHV and EBV, in addition to distinct genetic architectures resulting in important differences in pathogenesis and transmission.
A neurovascular high-frequency optical coherence tomography system enables in situ cerebrovascular volumetric microscopy
Authors: Ughi Giovanni J. , Marosfoi Miklos G. , King Robert M. , Caroff Jildaz , Peterson Lindsy M. , Duncan Benjamin H. , Langan Erin T. , Collins Amanda , Leporati Anita , Rousselle Serge , Lopes Demetrius K. , Gounis Matthew J. , Puri Ajit S. 
Published: July 2020

AbstractIntravascular imaging has emerged as a valuable tool for the treatment of coronary and peripheral artery disease; however, no solution is available for safe and reliable use in the tortuous vascular anatomy of the brain. Endovascular treatment of stroke is delivered under image guidance with insufficient resolution to adequately assess underlying arterial pathology and therapeutic devices. High-resolution imaging, enabling surgeons to visualize cerebral arteries' microstructure and micron-level features of neurovascular devices, would have a profound impact in the research, diagnosis, and treatment of cerebrovascular diseases. Here, we present a neurovascular high-frequency optical coherence tomography (HF-OCT) system, including an imaging console and an endoscopic probe designed to rapidly acquire volumetric microscopy data at a resolution approaching 10 microns in tortuous cerebrovascular anatomies. Using a combination of in vitro, ex vivo, and in vivo models, the feasibility of HF-OCT for cerebrovascular imaging was demonstrated.
Theoretical and empirical quantification of the accuracy of polygenic scores in ancestry divergent populations
Authors: Wang Ying , Guo Jing , Ni Guiyan , Yang Jian , Visscher Peter M. , Yengo Loic 
Published: July 2020

AbstractPolygenic scores (PGS) have been widely used to predict disease risk using variants identified from genome-wide association studies (GWAS). To date, most GWAS have been conducted in populations of European ancestry, which limits the use of GWAS-derived PGS in non-European ancestry populations. Here, we derive a theoretical model of the relative accuracy (RA) of PGS across ancestries. We show through extensive simulations that the RA of PGS based on genome-wide significant SNPs can be predicted accurately from modelling linkage disequilibrium (LD), minor allele frequencies (MAF), cross-population correlations of causal SNP effects and heritability. We find that LD and MAF differences between ancestries can explain between 70 and 80% of the loss of RA of European-based PGS in African ancestry for traits like body mass index and type 2 diabetes. Our results suggest that causal variants underlying common genetic variation identified in European ancestry GWAS are mostly shared across continents.