bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epitope-specific immunity against Staphylococcus aureus coproporphyrinogen III oxidase
Authors: Klimka Alexander , Mertins Sonja , Nicolai Anne Kristin , Rummler Liza Marie , Higgins Paul G. , Günther Saskia Diana , Tosetti Bettina , Krut Oleg , Krönke Martin 
Published: January 2021

AbstractStaphylococcus aureus represents a serious infectious threat to global public health and a vaccine against S. aureus represents an unmet medical need. We here characterise two S. aureus vaccine candidates, coproporphyrinogen III oxidase (CgoX) and triose phosphate isomerase (TPI), which fulfil essential housekeeping functions in heme synthesis and glycolysis, respectively. Immunisation with rCgoX and rTPI elicited protective immunity against S. aureus bacteremia. Two monoclonal antibodies (mAb), CgoX-D3 and TPI-H8, raised against CgoX and TPI, efficiently provided protection against S. aureus infection. MAb-CgoX-D3 recognised a linear epitope spanning 12 amino acids (aa), whereas TPI-H8 recognised a larger discontinuous epitope. The CgoX-D3 epitope conjugated to BSA elicited a strong, protective immune response against S. aureus infection. The CgoX-D3 epitope is highly conserved in clinical S. aureus isolates, indicating its potential wide usability against S. aureus infection. These data suggest that immunofocusing through epitope-based immunisation constitutes a strategy for the development of a S. aureus vaccine with greater efficacy and better safety profile.
Identification of a neutralizing epitope within minor repeat region of Plasmodium falciparum CS protein
Authors: Calvo-Calle J. Mauricio , Mitchell Robert , Altszuler Rita , Othoro Caroline , Nardin Elizabeth 
Published: January 2021

AbstractMalaria remains a major cause of morbidity and mortality worldwide with 219 million infections and 435,000 deaths predominantly in Africa. The infectivePlasmodiumsporozoite is the target of a potent humoral immune response that can protect murine, simian and human hosts against challenge by malaria-infected mosquitoes. Early murine studies demonstrated that sporozoites or subunit vaccines based on the sporozoite major surface antigen, the circumsporozoite (CS) protein, elicit antibodies that primarily target the central repeat region of the CS protein. In the current murine studies, using monoclonal antibodies and polyclonal sera obtained following immunization withP. falciparumsporozoites or synthetic repeat peptides, we demonstrate differences in the ability of these antibodies to recognize the major and minor repeats contained in the central repeat region. The biological relevance of these differences in fine specificity was explored using a transgenicP. bergheirodent parasite expressing theP. falciparumCS repeat region. In these in vitro and in vivo studies, we demonstrate that the minor repeat region, comprised of three copies of alternating NANP and NVDP tetramer repeats, contains an epitope recognized by sporozoite-neutralizing antibodies. In contrast, murine monoclonal antibodies specific for the major CS repeats (NANP)ncould be isolated from peptide-immunized mice that had limited or no sporozoite-neutralizing activity. These studies highlight the importance of assessing the fine specificity and functions of antirepeat antibodies elicited byP. falciparumCS-based vaccines and suggest that the design of immunogens to increase antibody responses to minor CS repeats may enhance vaccine efficacy.
Giant lungfish genome elucidates the conquest of land by vertebrates
Authors: Meyer Axel , Schloissnig Siegfried , Franchini Paolo , Du Kang , Woltering Joost M. , Irisarri Iker , Wong Wai Yee , Nowoshilow Sergej , Kneitz Susanne , Kawaguchi Akane , Fabrizius Andrej , Xiong Peiwen , Dechaud Corentin , Spaink Herman P. , Volff Jean-Nicolas , Simakov Oleg , Burmester Thorsten , Tanaka Elly M. , Schartl Manfred 
Published: January 2021

AbstractLungfishes belong to lobe-fined fish (Sarcopterygii) that, in the Devonian period, ‘conquered’ the land and ultimately gave rise to all land vertebrates, including humans1–3. Here we determine the chromosome-quality genome of the Australian lungfish (Neoceratodus forsteri), which is known to have the largest genome of any animal. The vast size of this genome, which is about 14× larger than that of humans, is attributable mostly to huge intergenic regions and introns with high repeat content (around 90%), the components of which resemble those of tetrapods (comprising mainly long interspersed nuclear elements) more than they do those of ray-finned fish. The lungfish genome continues to expand independently (its transposable elements are still active), through mechanisms different to those of the enormous genomes of salamanders. The 17 fully assembled lungfish macrochromosomes maintain synteny to other vertebrate chromosomes, and all microchromosomes maintain conserved ancient homology with the ancestral vertebrate karyotype. Our phylogenomic analyses confirm previous reports that lungfish occupy a key evolutionary position as the closest living relatives to tetrapods4,5, underscoring the importance of lungfish for understanding innovations associated with terrestrialization. Lungfish preadaptations to living on land include the gain of limb-like expression in developmental genes such as hoxc13 and sall1 in their lobed fins. Increased rates of evolution and the duplication of genes associated with obligate air-breathing, such as lung surfactants and the expansion of odorant receptor gene families (which encode proteins involved in detecting airborne odours), contribute to the tetrapod-like biology of lungfishes. These findings advance our understanding of this major transition during vertebrate evolution.
High energy implementation of coil-target scheme for guided re-acceleration of laser-driven protons
Authors: Ahmed Hamad , Hadjisolomou Prokopis , Naughton Kealan , Alejo Aaron , Brauckmann Stephanie , Cantono Giada , Ferguson Simon , Cerchez Mirela , Doria Domenico , Green James , Gwynne Deborah , Hodge Thomas , Kumar Deepak , Macchi Andrea , Prasad Rajendra , Willi Oswald , Borghesi Marco , Kar Satyabrata 
Published: January 2021

AbstractDeveloping compact ion accelerators using intense lasers is a very active area of research, motivated by a strong applicative potential in science, industry and healthcare. However, proposed applications in medical therapy, as well as in nuclear and particle physics demand a strict control of ion energy, as well as of the angular and spectral distribution of ion beam, beyond the intrinsic limitations of the several acceleration mechanisms explored so far. Here we report on the production of highly collimated ($$\sim 0.2^{\circ }$$

∼
0
.

2
∘

half angle divergence), high-charge (10s of pC) and quasi-monoenergetic proton beams up to $$\sim$$
∼
50 MeV, using a recently developed method based on helical coil targetry. In this concept, ions accelerated from a laser-irradiated foil are post-accelerated and conditioned in a helical structure positioned at the rear of the foil. The pencil beam of protons was produced by guided post-acceleration at a rate of $$\sim$$
∼
2 GeV/m, without sacrificing the excellent beam emittance of the laser-driven proton beams. 3D particle tracing simulations indicate the possibility of sustaining high acceleration gradients over extended helical coil lengths, thus maximising the gain from such miniature accelerating modules.
Optimal pulse length of insonification for Piezo1 activation and intracellular calcium response
Authors: Liao Defei , Hsiao Ming-Yen , Xiang Gaoming , Zhong Pei 
Published: January 2021

AbstractUltrasound (US) neuromodulation, especially sonogenetics, has been demonstrated with potential applications in noninvasive and targeted treatment of various neurological disorders. Despite the growing interest, the mechanism for US neuromodulation remains elusive, and the optimal condition for eliciting a neural response with minimal adverse effect has not been identified. Here, we investigate the Piezo1 activation and intracellular calcium response elicited by acoustical streaming induced shear stress under various US exposure conditions. We find that Piezo1 activation and resultant intracellular calcium response depend critically on shear stress amplitude and pulse length of the stimulation. Under the same insonification acoustic energy, we further identify an optical pulse length that leads to maximum cell deformation, Piezo1 activation, and calcium response with minimal injury, confirmed by numerical modeling of Piezo1 channel gating dynamics. Our results provide insight into the mechanism of ultrasonic activation of Piezo1 and highlight the importance of optimizing US exposure conditions in sonogenetics applications.
A comprehensive analysis of the phylogenetic signal in ramp sequences in 211 vertebrates
Authors: McKinnon Lauren M. , Miller Justin B. , Whiting Michael F. , Kauwe John S. K. , Ridge Perry G. 
Published: January 2021

AbstractRamp sequences increase translational speed and accuracy when rare, slowly-translated codons are found at the beginnings of genes. Here, the results of the first analysis of ramp sequences in a phylogenetic construct are presented. Ramp sequences were compared from 247 vertebrates (114 Mammalian and 133 non-mammalian), where the presence and absence of ramp sequences was analyzed as a binary character in a parsimony and maximum likelihood framework. Additionally, ramp sequences were mapped to the Open Tree of Life synthetic tree to determine the number of parallelisms and reversals that occurred, and those results were compared to random permutations. Parsimony and maximum likelihood analyses of the presence and absence of ramp sequences recovered phylogenies that are highly congruent with established phylogenies. Additionally, 81% of vertebrate mammalian ramps and 81.2% of other vertebrate ramps had less parallelisms and reversals than the mean from 1000 randomly permuted trees. A chi-square analysis of completely orthologous ramp sequences resulted in a p-value < 0.001 as compared to random chance. Ramp sequences recover comparable phylogenies as other phylogenomic methods. Although not all ramp sequences appear to have a phylogenetic signal, more ramp sequences track speciation than expected by random chance. Therefore, ramp sequences may be used in conjunction with other phylogenomic approaches if many orthologs are taken into account. However, phylogenomic methods utilizing few orthologs should be cautious in incorporating ramp sequences because individual ramp sequences may provide conflicting signals.
Role of physical activity and fitness on sleep in sedentary middle-aged adults: the FIT-AGEING study
Authors: Mochón-Benguigui Sol , Carneiro-Barrera Almudena , Castillo Manuel J. , Amaro-Gahete Francisco J. 
Published: January 2021

AbstractThe association of physical activity and fitness with sleep still remains unclear since there is a lack of studies in this field of research using objective measurements of these variables. This study aimed to investigate the association of objectively-measured sedentariness, physical activity levels, and physical fitness with sleep quantity and quality in sedentary middle-aged adults. A total of 74 volunteers (52.7% women; aged 53.7 ± 5.1) were recruited for the present study. Cardiorespiratory fitness was measured through a maximal treadmill test, and muscular strength by extension and flexion peak torque, and by the hand grip test. Physical activity and objective sleep parameters were determined through accelerometry, and subjective sleep by the Pittsburgh Sleep Quality Index (PSQI). Reduced levels of sedentariness, greater VO2max, and greater muscular strength were positively related to improved objective sleep quantity and quality (all P ≤ 0.05). Furthermore, higher levels of overall physical activity, VO2max, and muscular strength were related to better subjective sleep quantity and quality (all P ≤ 0.05). Reduced sedentariness and increased physical activity and fitness may be a potential prevention and/or treatment pathway to reduce sleep disturbances and, in general, to improve patients physical and psychological health for a successful aging process.
Molecular analyses identifies new domains and structural differences among Streptococcus pneumoniae immune evasion proteins PspC and Hic
Authors: Du Shanshan , Vilhena Cláudia , King Samantha , Sahagún-Ruiz Alfredo , Hammerschmidt Sven , Skerka Christine , Zipfel Peter F. 
Published: January 2021

AbstractThe PspC and Hic proteins of Streptococcuspneumoniae are some of the most variable microbial immune evasion proteins identified to date. Due to structural similarities and conserved binding profiles, it was assumed for a long time that these pneumococcal surface proteins represent a protein family comprised of eleven subgroups. Recently, however, the evaluation of more proteins revealed a greater diversity of individual proteins. In contrast to previous assumptions a pattern evaluation of six PspC and five Hic variants, each representing one of the previously defined subgroups, revealed distinct structural and likely functionally regions of the proteins, and identified nine new domains and new domain alternates. Several domains are unique to PspC and Hic variants, while other domains are also present in other virulence factors encoded by pneumococci and other bacterial pathogens. This knowledge improved pattern evaluation at the level of full-length proteins, allowed a sequence comparison at the domain level and identified domains with a modular composition. This novel strategy increased understanding of individual proteins variability and modular domain composition, enabled a structural and functional characterization at the domain level and furthermore revealed substantial structural differences between PspC and Hic proteins. Given the exceptional genomic diversity of the multifunctional PspC and Hic proteins a detailed structural and functional evaluation need to be performed at the strain level. Such knowledge will also be useful for molecular strain typing and characterizing PspC and Hic proteins from new clinical S. pneumoniae strains.
Nutritional status and anxious and depressive symptoms in anorexia nervosa: a prospective study
Authors: Pleplé A. , Lalanne C. , Huas C. , Mattar L. , Hanachi M. , Flament M. F. , Carchon I. , Jouen F. , Berthoz S. , Godart N. 
Published: January 2021

AbstractThe interweaving of malnutrition and symptoms of anxiety and depression in anorexia Nervosa (AN) is mentioned without any consensus regarding the course of anxious-depressive symptoms in relation to nutritional status in the course of treatment of patients with AN. The objectives of the current study in a large sample of AN inpatients were to assess the relationships between anxiety and depression symptoms and nutritional status both over the course of inpatient treatment and at discharge. 222 consecutive inpatients with AN (DSM-IV TR) were assessed (entrance and discharge) for duration of illness, psychiatric treatments, sociodemographic data and with psychometric scales for different psychopathological symptoms [depressive (BDI), anxiety and depressive (HAD scale), obsessive–compulsive (MOCI) and social phobia (LSAS fear score)]. Nutritional status was assessed with Body Mass Index (BMI) and body composition by bioelectrical impedance. The Fat free mass index [FFMI = FFM (kg)/height (m2)] was considered for the analysis. Two models were developed where the dependent variables were each psychopathological score at discharge (BDI, HAD anxiety, MOCI, and LSAS fear) in the cross-sectional model, and their variation in the longitudinal model (where a positive score reflected symptom decrease at discharge). A fixed set of predictors, defined on presumed clinical and statistical relevance (FFMI in the cross-sectional model and Variation of FFMI in the longitudinal model), were considered in each model, without any model selection procedure. This is the first study to confirm a positive relationship between the course of eating disorder symptoms and that of anxious-depressive symptoms during inpatient treatment of AN even after adjustment on a vast array of possibly confounding factors.
Modelling normal age-related changes in individual retinal layers using location-specific OCT analysis
Authors: Trinh Matt , Khou Vincent , Zangerl Barbara , Kalloniatis Michael , Nivison-Smith Lisa 
Published: January 2021

AbstractCurrent descriptions of retinal thickness across normal age cohorts are mostly limited to global analyses, thus overlooking spatial variation across the retina and limiting spatial analyses of retinal and optic nerve disease. This retrospective cross-sectional study uses location-specific cluster analysis of 8 × 8 macular average grid-wise thicknesses to quantify topographical patterns and rates of normal, age-related changes in all individual retinal layers of 253 eyes of 253 participants across various age cohorts (n = 23–69 eyes per decade). Most retinal layers had concentric spatial cluster patterns except the retinal nerve fibre layer (RNFL) which displayed a nasal, asymmetric radial pattern. Age-related thickness decline mostly occurred after the late 4th decade, described by quadratic regression models. The ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer nuclear layer + Henle’s fibre layer (ONL+HFL) were significantly associated with age (p < 0.0001 to < 0.05), demonstrating similar rates of thickness decline (mean pooled slope =  − 0.07 µm/year), while the IS/OS had lesser mean pooled thickness slopes for all clusters (− 0.04 µm/year). The RNFL, OPL, and RPE exhibited no significant age-related thickness change, and the RNFL were significantly associated with sex. Analysis using spatial clusters compared to the ETDRS sectors revealed more extensive spatial definition and less variability in the former method. These spatially defined, clustered normative data and age-correction functions provide an accessible method of retinal thickness analysis with more spatial detail and less variability than the ETDRS sectors, potentially aiding the diagnosis and monitoring of retinal and optic nerve disease.
Human ex vivo lung perfusion: a novel model to study human lung diseases
Authors: Cárdenes Nayra , Sembrat John , Noda Kentaro , Lovelace Tyler , Álvarez Diana , Bittar Humberto E. Trejo , Philips Brian J. , Nouraie Mehdi , Benos Panayiotis V. , Sánchez Pablo G. , Rojas Mauricio 
Published: January 2021

AbstractExperimental animal models to predict physiological responses to injury and stress in humans have inherent limitations. Therefore, the development of preclinical human models is of paramount importance. Ex vivo lung perfusion (EVLP) has typically been used to recondition donor lungs before transplantation. However, this technique has recently advanced into a model to emulate lung mechanics and physiology during injury. In the present study, we propose that the EVLP of diseased human lungs is a well-suited preclinical model for translational research on chronic lung diseases. Throughout this paper, we demonstrate this technique's feasibility in pulmonary arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF), emphysema, and non-disease donor lungs not suitable for transplantation. In this study, we aimed to perfuse the lungs for 6 h with the EVLP system. This facilitated a robust and continuous assessment of airway mechanics, pulmonary hemodynamics, gas exchange, and biochemical parameters. We then collected at different time points tissue biopsies of lung parenchyma to isolate RNA and DNA to identify each disease's unique gene expression. Thus, demonstrating that EVLP could successfully serve as a clinically relevant experimental model to derive essential insights into pulmonary pathophysiology and various human lung diseases.
Temperature dependence for high electrical performance of Mn-doped high surface area activated carbon (HSAC) as additives for hybrid capacitor
Authors: Otgonbayar Zambaga , Fatema Kamrun Nahar , Yang Sunhye , Kim Ick-Jun , Kim Minchul , Shim Sang Eun , Oh Won-Chun 
Published: January 2021

AbstractHerein, we manufactured the positive and negative electrodes for the hybrid capacitor. The Mn-doped High surface area of Activated carbon composite used for the positive electrode and as-prepared composite was calcined at 600 °C and 800 °C. The morphological structures and pore-size distributions of MnYP-600HTT and MnYP-800HTT were characterized by means of XRD, SEM, EDAX, TEM, and BET. According to the BET specific surface-area evaluation, MnYP-600HTT and MnYP-800HTT were 1272.6 and 1388.1 m2/g, respectively. Total pore volumes were 0.627 and 0.687 cm3/g, which is beneficial for forming ion-transport channels in electrochemical reactions. The MnYP-600HTT electrode had a high specific capacity of 177.2 mAh/g at 20C, and the capacity retention was 64.8%. During the entire cycling, MnYP-600HTT had excellent cyclic stability in 500 cycles along with high efficiency. The robust design of the MnYP-600HTT and MnYP-800HTT cathode materials introduced in this work pave the way for designing next-generation supercapacitors operating at ultra-high C rates. The Mn-doped high surface of activated carbon had stable energy density and superior cycling stability that were demonstrated in supercapacitor systems.
Integration of genome-wide association study and expression quantitative trait locus mapping for identification of endometriosis-associated genes
Authors: Chou Ya-Ching , Chen Ming-Jer , Chen Pi-Hua , Chang Ching-Wen , Yu Mu-Hsien , Chen Yi-Jen , Tsai Eing-Mei , Tsai Shih-Feng , Kuo Wun-Syuan , Tzeng Chii-Ruey 
Published: January 2021

AbstractTo determine whether genetic predisposition to endometriosis varies depending on ethnicity and in association with expression quantitative trait loci (eQTL) in a Taiwanese population. We conducted a genome-wide association study (GWAS) and replicated it in 259 individuals with laparoscopy-confirmed stage III or IV endometriosis (cases) and 171 women without endometriosis (controls). Their genomic DNA was extracted from blood and evaluated by the GWAS of Taiwan Biobank Array. Novel genetic variants that predispose individuals to endometriosis were identified using GWAS and replication, including rs10739199 (P = 6.75 × 10−5) and rs2025392 (P = 8.01 × 10−5) at chromosome 9, rs1998998 (P = 6.5 × 10−6) at chromosome 14, and rs6576560 (P = 9.7 × 10−6) at chromosome 15. After imputation, strong signals were exhibited by rs10822312 (P = 1.80 × 10−7) at chromosome 10, rs58991632 (P = 1.92 × 10−6) and rs2273422 (P = 2.42 × 10−6) at chromosome 20, and rs12566078 (P = 2.5 × 10−6) at chromosome 1. We used the Genotype-Tissue Expression (GTEx) database to observe eQTL. Among these SNPs, the cis-eQTL rs13126673 of inturned planar cell polarity protein (INTU) showed significant association with INTU expression (P = 5.1 × 10–33). Moreover, the eQTL analysis was performed on endometriotic tissues from women with endometriosis. The expression of INTU in 78 endometriotic tissue of women with endometriosis is associated with rs13126673 genotype (P = 0.034). To our knowledge, this is the first GWAS to link endometriosis and eQTL in a Taiwanese population.