bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive selection and intrinsic disorder are associated with multifunctional C4(AC4) proteins and geminivirus diversification
Authors: Deom Carl Michael , Brewer Marin Talbot , Severns Paul M. 
Published: May 2021

AbstractViruses within the Geminiviridae family cause extensive agricultural losses. Members of four genera of geminiviruses contain a C4 gene (AC4 in geminiviruses with bipartite genomes). C4(AC4) genes are entirely overprinted on the C1(AC1) genes, which encode the replication-associated proteins. The C4(AC4) proteins exhibit diverse functions that may be important for geminivirus diversification. In this study, the influence of natural selection on the evolutionary diversity of 211 C4(AC4) genes relative to the C1(AC1) sequences they overlap was determined from isolates of the Begomovirus and Curtovirus genera. The ratio of nonsynonymous (dN) to synonymous (dS) nucleotide substitutions indicated that C4(AC4) genes are under positive selection, while the overlapped C1(AC1) sequences are under purifying selection. Ninety-one of 200 Begomovirus C4(AC4) genes encode elongated proteins with the extended regions being under neutral selection. C4(AC4) genes from begomoviruses isolated from tomato from native versus exotic regions were under similar levels of positive selection. Analysis of protein structure suggests that C4(AC4) proteins are entirely intrinsically disordered. Our data suggest that non-synonymous mutations and mutations that increase the length of C4(AC4) drive protein diversity that is intrinsically disordered, which could explain C4/AC4 functional variation and contribute to both geminivirus diversification and host jumping.
A novel system for intensive Diadema antillarum propagation as a step towards population enhancement
Authors: Pilnick Aaron R. , O’Neil Keri L. , Moe Martin , Patterson Joshua T. 
Published: May 2021

AbstractThe long-spined sea urchin Diadema antillarum was once an abundant reef grazing herbivore throughout the Caribbean. During the early 1980s, D. antillarum populations were reduced by > 93% due to an undescribed disease. This event resulted in a lack of functional reef herbivory and contributed to ongoing ecological shifts from hard coral towards macroalgae dominated reefs. Limited natural recovery has increased interest in a range of strategies for augmenting herbivory. An area of focus has been developing scalable ex situ methods for rearing D. antillarum from gametes. The ultimate use of such a tool would be exploring hatchery origin restocking strategies. Intensive ex situ aquaculture is a potentially viable, yet difficult, method for producing D. antillarum at scales necessary to facilitate restocking. Here we describe a purpose-built, novel recirculating aquaculture system and the broodstock management and larval culture process that has produced multiple D. antillarum cohorts, and which has the potential for practical application in a dedicated hatchery setting. Adult animals held in captivity can be induced to spawn year-round, with some evidence for annual and lunar periodicity. Fecundity and fertilization rates are both consistently very high, yet challenges persist in both late stage larval development and early post-settlement survival. Initial success was realized with production of 100 juvenile D. antillarum from ~ 1200 competent larvae. While the system we describe requires a significant level of investment and technical expertise, this work advances D. antillarum culture efforts in potential future hatchery settings and improves the viability of scalable ex situ production for population enhancement.
Gene expression alterations in salivary gland epithelia of Sjögren’s syndrome patients are associated with clinical and histopathological manifestations
Authors: Dela Cruz Ariana , Kartha Vinay , Tilston-Lunel Andrew , Mi Rongjuan , Reynolds Taylor L. , Mingueneau Michael , Monti Stefano , Jensen Janicke L. , Skarstein Kathrine , Varelas Xaralabos , Kukuruzinska Maria A. 
Published: May 2021

AbstractSjögren’s syndrome (SS) is a complex autoimmune disease associated with lymphocytic infiltration and secretory dysfunction of salivary and lacrimal glands. Although the etiology of SS remains unclear, evidence suggests that epithelial damage of the glands elicits immune and fibrotic responses in SS. To define molecular changes underlying epithelial tissue damage in SS, we laser capture microdissected (LCM) labial salivary gland epithelia from 8 SS and 8 non-SS controls for analysis by RNA sequencing (RNAseq). Computational interrogation of gene expression signatures revealed that, in addition to a division of SS and non-SS samples, there was a potential intermediate state overlapping clustering of SS and non-SS samples. Differential expression analysis uncovered signaling events likely associated with distinct SS pathogenesis. Notable signals included the enrichment of IFN-γ and JAK/STAT-regulated genes, and the induction of genes encoding secreted factors, such as LTF, BMP3, and MMP7, implicated in immune responses, matrix remodeling and tissue destruction. Identification of gene expression signatures of salivary epithelia associated with mixed clinical and histopathological characteristics suggests that SS pathology may be defined by distinct molecular subtypes. We conclude that gene expression changes arising in the damaged salivary epithelia may offer novel insights into the signals contributing to SS development and progression.
Muscle metabolome and adipose tissue mRNA expression of lipid metabolism-related genes in over-conditioned dairy cows differing in serum-metabotype
Authors: Sadri Hassan , Ghaffari Morteza Hosseini , Schuh Katharina , Koch Christian , Sauerwein Helga 
Published: May 2021

AbstractOver-conditioned dairy cows, classified by body condition score (BCS) and backfat thickness (BFT) are less able to metabolically adapt to the rapidly increasing milk yield after parturition. Based on serum metabolome and cluster analyses, high BCS cows (HBCS) could be classified into metabotypes that are more similar to normal (NBCS) cows, i.e., HBCS predicted normal (HBCS-PN) than the HBCS predicted high (HBCS-PH) cows—similar to the concept of obese but metabolically healthy humans. Our objective was to compare muscle metabolome and mRNA abundance of genes related to lipogenesis and lipolysis in adipose tissue between HBCS-PH (n = 13), HBCS-PN (n = 6), and NBCS-PN (n = 15). Tail-head subcutaneous fat was biopsied on d −49, 3, 21, and 84 relative to parturition. Potential differences in the oxidative capacity of skeletal muscle were assessed by targeted metabolomics in M. semitendinosus from d 21. Besides characteristic changes with time, differences in the mRNA abundance were limited to lipogenesis-related genes on d −49 (HBCS-PH > HBCS-PN). The HBCS-PH had more than two-fold higher muscle concentrations of short (C2, C4-OH, C6-OH) and long-chain acylcarnitines (C16, C18, and C18:1) than HBCS-PN, indicating a greater oxidative capacity for fatty acids (and utilization of ketones) in muscle of HBCS-PN than HBCS-PH cows.
Discovery of cryptic plant diversity on the rooftops of the Alps
Authors: Boucher Florian C. , Dentant Cédric , Ibanez Sébastien , Capblancq Thibaut , Boleda Martí , Boulangeat Louise , Smyčka Jan , Roquet Cristina , Lavergne Sébastien 
Published: May 2021

AbstractHigh elevation temperate mountains have long been considered species poor owing to high extinction or low speciation rates during the Pleistocene. We performed a phylogenetic and population genomic investigation of an emblematic high-elevation plant clade (Androsace sect. Aretia, 31 currently recognized species), based on plant surveys conducted during alpinism expeditions. We inferred that this clade originated in the Miocene and continued diversifying through Pleistocene glaciations, and discovered three novel species of Androsace dwelling on different bedrock types on the rooftops of the Alps. This highlights that temperate high mountains have been cradles of plant diversity even during the Pleistocene, with in-situ speciation driven by the combined action of geography and geology. Our findings have an unexpected historical relevance: H.-B. de Saussure likely observed one of these species during his 1788 expedition to the Mont Blanc and we describe it here, over two hundred years after its first sighting.
Dynamic modulation of social influence by indirect reciprocity
Authors: Zonca Joshua , Folsø Anna , Sciutti Alessandra 
Published: May 2021

AbstractIndirect reciprocity is a pervasive social norm that promotes human cooperation. Helping someone establishes a good reputation, increasing the probability of receiving help from others. Here we hypothesize that indirect reciprocity regulates not only cooperative behavior but also the exchange of opinions within a social group. In a novel interactive perceptual task (Experiment 1), we show that participants relied more on the judgments of an alleged human partner when a second alleged peer had been endorsing participants’ opinions. By doing so, participants did not take into account the reliability of their partners’ judgments and did not maximize behavioral accuracy and monetary reward. This effect declined when participants did not expect future interactions with their partners, suggesting the emergence of downstream mechanisms of reciprocity linked to the management of reputation. Importantly, all these effects disappeared when participants knew that the partners’ responses were computer-generated (Experiment 2). Our results suggest that, within a social group, individuals may weight others’ opinions through indirect reciprocity, highlighting the emergence of normative distortions in the process of information transmission among humans.
Penetration of sweet cherry skin by 45Ca-salts: pathways and factors
Authors: Winkler Andreas , Knoche Moritz 
Published: May 2021

AbstractCalcium is beneficial to sweet cherry physiology. The objective was to investigate factors affecting uptake of Ca into mature sweet cherry fruit through their skins. Penetration of 45Ca-salts was monitored using whole fruit or excised fruit skins mounted in diffusion cells. Penetration of 45CaCl2 into intact fruit and through excised skins increased with time. Sealing the pedicel/fruit junction decreased penetration, but sealing the stylar scar had no effect. There was little difference in permeances of the fruit skin to 45CaCl2, 45Ca(NO3)2, 45Ca-formate, 45Ca-acetate, 45Ca-lactate or 45Ca-propionate. Only 45Ca-heptagluconate penetrated at a slower rate. Increasing temperature markedly increased Ca-penetration. Penetration was most rapid at 35 °C, intermediate at 22 °C and slowest at 12 °C. Increasing relative humidity (RH) from 0, 28, 75 to 100% increased penetration of 45CaCl2, but penetration of 45Ca-formate was restricted to 100% RH. Increasing the RH from 50 to 100% at 96 h after droplet application had no effect on penetration of 45CaCl2, but increased penetration of 45Ca-formate. The results reveal that: (1) the fruit/pedicel junction is a site of preferential Ca-uptake and (2) Ca-penetration is limited by the mobility of the Ca ion in the dried-down droplet residue when the point of deliquescence of the applied salt exceeds the ambient RH.
Kefir metabolites in a fly model for Alzheimer’s disease
Authors: Batista Letícia Leandro , Malta Serena Mares , Guerra Silva Heitor Cappato , Borges Luiza Diniz Ferreira , Rocha Lays Oliveira , da Silva Jéssica Regina , Rodrigues Tamiris Sabrina , Venturini Gabriela , Padilha Kallyandra , da Costa Pereira Alexandre , Espindola Foued Salmen , Ueira-Vieira Carlos 
Published: May 2021

AbstractAlzheimer’s Disease (AD) is the most common cause of dementia among elderly individuals worldwide, leading to a strong motor-cognitive decline and consequent emotional distress and codependence. It is traditionally characterized by amyloidogenic pathway formation of senile plaques, and recent studies indicate that dysbiosis is also an important factor in AD’s pathology. To overcome dysbiosis, probiotics—as kefir—have shown to be a great therapeutic alternative for Alzheimer’s disease. In this present work, we explored kefir as a probiotic and a metabolite source as a modulator of microbiome and amyloidogenic pathway, using a Drosophila melanogaster model for AD (AD-like flies). Kefir microbiota composition was determined through 16S rRNA sequencing, and the metabolome of each fraction (hexane, dichloromethane, ethyl acetate, and n-butanol) was investigated. After treatment, flies had their survival, climbing ability, and vacuolar lesions accessed. Kefir and fraction treated flies improved their climbing ability survival rate and neurodegeneration index. In conclusion, we show that kefir in natura, as well as its fractions may be promising therapeutic source against AD, modulating amyloidogenic related pathways.
Small molecule inhibitors of the mitochondrial ClpXP protease possess cytostatic potential and re-sensitize chemo-resistant cancers
Authors: Meßner Martina , Mandl Melanie M. , Hackl Mathias W. , Reinhardt Till , Ardelt Maximilian A. , Szczepanowska Karolina , Frädrich Julian E. , Waschke Jens , Jeremias Irmela , Fux Anja , Stahl Matthias , Vollmar Angelika M. , Sieber Stephan A. , Pachmayr Johanna 
Published: May 2021

AbstractThe human mitochondrial ClpXP protease complex (HsClpXP) has recently attracted major attention as a target for novel anti-cancer therapies. Despite its important role in disease progression, the cellular role of HsClpXP is poorly characterized and only few small molecule inhibitors have been reported. Herein, we screened previously established S. aureus ClpXP inhibitors against the related human protease complex and identified potent small molecules against human ClpXP. The hit compounds showed anti-cancer activity in a panoply of leukemia, liver and breast cancer cell lines. We found that the bacterial ClpXP inhibitor 334 impairs the electron transport chain (ETC), enhances the production of mitochondrial reactive oxygen species (mtROS) and thereby promotes protein carbonylation, aberrant proteostasis and apoptosis. In addition, 334 induces cell death in re-isolated patient-derived xenograft (PDX) leukemia cells, potentiates the effect of DNA-damaging cytostatics and re-sensitizes resistant cancers to chemotherapy in non-apoptotic doses.
The association between four scoring systems and 30-day mortality among intensive care patients with sepsis: a cohort study
Authors: Hu Tianyang , Lv Huajie , Jiang Youfan 
Published: May 2021

AbstractSeveral commonly used scoring systems (SOFA, SAPS II, LODS, and SIRS) are currently lacking large sample data to confirm the predictive value of 30-day mortality from sepsis, and their clinical net benefits of predicting mortality are still inconclusive. The baseline data, LODS score, SAPS II score, SIRS score, SOFA score, and 30-day prognosis of patients who met the diagnostic criteria of sepsis were retrieved from the Medical Information Mart for Intensive Care III (MIMIC-III) intensive care unit (ICU) database. Receiver operating characteristic (ROC) curves and comparisons between the areas under the ROC curves (AUC) were conducted. Decision curve analysis (DCA) was performed to determine the net benefits between the four scoring systems and 30-day mortality of sepsis. For all cases in the cohort study, the AUC of LODS, SAPS II, SIRS, SOFA were 0.733, 0.787, 0.597, and 0.688, respectively. The differences between the scoring systems were statistically significant (all P-values < 0.0001), and stratified analyses (the elderly and non-elderly) also showed the superiority of SAPS II among the four systems. According to the DCA, the net benefit ranges in descending order were SAPS II, LODS, SOFA, and SIRS. For stratified analyses of the elderly or non-elderly groups, the results also showed that SAPS II had the most net benefit. Among the four commonly used scoring systems, the SAPS II score has the highest predictive value for 30-day mortality from sepsis, which is better than LODS, SIRS, and SOFA. The results of the DCA curves show that using the SAPS II score to predict the 30-day mortality of intensive care patients with sepsis to guide clinical applications may obtain the highest net benefit.
Designing a multi-epitope vaccine against Mycobacteroides abscessus by pangenome-reverse vaccinology
Authors: Dar Hamza Arshad , Ismail Saba , Waheed Yasir , Ahmad Sajjad , Jamil Zubia , Aziz Hafsa , Hetta Helal F. , Muhammad Khalid 
Published: May 2021

AbstractMycobacteroides abscessus (Previously Mycobacterium abscessus) is an emerging microorganism of the newly defined genera Mycobacteroides that causes mainly skin and tissue diseases in humans. The recent availability of total 34 fully sequenced genomes of different strains belonging to this species has provided an opportunity to utilize this genomics data to gain novel insights and guide the development of specific antimicrobial therapies. In the present study, we collected collectively 34 complete genome sequences of M. abscessus from the NCBI GenBank database. Pangenome analysis was conducted on these genomes to understand the genetic diversity and to obtain proteins associated with its core genome. These core proteins were then subjected to various subtractive filters to identify potential antigenic targets that were subjected to multi-epitope vaccine design. Our analysis projected the open pangenome of M. abscessus containing 3443 core genes. After applying various stepwise filtration steps on the core proteins, a total of four potential antigenic targets were identified. Utilizing their constituent CD4 and CD8 T-cell epitopes, a multi-epitope based subunit vaccine was computationally designed. Sequence-based analysis as well as structural characterization revealed the immunological effectiveness of this designed vaccine. Further molecular docking, molecular dynamics simulation and binding free energy estimation with Toll-like receptor 2 indicated strong structural associations of the vaccine with the immune receptor. The promising results are encouraging and need to be validated by additional wet laboratory studies for confirmation.
Urban access across the globe: an international comparison of different transport modes
Authors: Wu Hao , Avner Paolo , Boisjoly Genevieve , Braga Carlos K. V. , El-Geneidy Ahmed , Huang Jie , Kerzhner Tamara , Murphy Brendan , Niedzielski Michał A. , Pereira Rafael H. M. , Pritchard John P. , Stewart Anson , Wang Jiaoe , Levinson David 
Published: May 2021

AbstractAccess (the ease of reaching valued destinations) is underpinned by land use and transport infrastructure. The importance of access in transport, sustainability, and urban economics is increasingly recognized. In particular, access provides a universal unit of measurement to examine cities for the efficiency of transport and land-use systems. This paper examines the relationship between population-weighted access and metropolitan population in global metropolitan areas (cities) using 30-min cumulative access to jobs for 4 different modes of transport; 117 cities from 16 countries and 6 continents are included. Sprawling development with the intensive road network in American cities produces modest automobile access relative to their sizes, but American cities lag behind globally in transit and walking access; Australian and Canadian cities have lower automobile access, but better transit access than American cities; combining compact development with an intensive network produces the highest access in Chinese and European cities for their sizes. Hence density and mobility co-produce better access. This paper finds access to jobs increases with populations sublinearly, so doubling the metropolitan population results in less than double access to jobs. The relationship between population and access characterizes regions, countries, and cities, and significant similarities exist between cities from the same country.
Table‐based formal specification approaches for control engineers—empirical studies of usability
Authors: Cha Suhyun , Vogel‐Heuser Birgit , Weigl Alexander , Ulbrich Mattias , Beckert Bernhard 
Published: May 2021

AbstractThe dependability characteristic of the control software of manufacturing systems is highlighted more than before, going through repeated changes to cope with various and varying requirements. Formal methods are researched to be applied to automation system engineering to obtain a more effective and efficient quality assurance. One of the approaches, a formal specification language named Generalised Test Tables has been developed with the aim of intuitiveness and accessibility for automation application developers. The result of the experiments conducted to assess the usability of this language is presented here. Focussing on evaluating effectiveness and user satisfaction, three paper‐based experiments have been conducted with students at the bachelor and master level. The evaluation results point to positive usability in both comparative effectiveness to conventional language, that is, Petri Nets, and subjective perception of user satisfaction.
Finite‐time convergence for bilateral teleoperation systems with disturbance and time‐varying delays
Authors: Dao Phuong Nam , Nguyen Van Tinh , Liu Yen‐Chen 
Published: May 2021

AbstractThis paper addresses the robust finite‐time sliding mode control algorithms for nonlinear bilateral teleoperators in the presence of variable time delays and disturbances. In this paper, the designs of terminal sliding control are proposed to guarantee the finite‐time convergence of not only the sliding variables but also the coordination errors on position tracking. The proposed control algorithm is able to ensure finite‐time convergence without requiring the relative velocities and power signal in the communication channel. Additionally, the finite‐time controller is developed with additional terms of sign and exponential function to tackle the variable time delay between two sides in bilateral teleoperators. The Lyapunov synthesis principle and additional lemmas are exploited to ensure the finite‐time stability of the closed‐loop system in the presence of delays and disturbance. The situations of free‐motion, passive, and non‐passive human/environment forces are considered for finite‐time convergence without the need of acceleration signals. Finally, numerical examples and experimental studies are carried out to illustrate the effectiveness of the proposed controllers.
A dual‐input DC‐DC structure with high voltage gain suggested for hybrid energy systems
Authors: Pourjafar Saeed , Shayeghi Hossein , Sedaghat Farzad , SeyedShenava SeyedJalal 
Published: May 2021

AbstractThis paper proposes a non‐isolated dual‐input DC‐DC converter with high voltage rate recommended for hybrid renewable sources/energy storage applications. The suggested converter can transfer power between two different sources in different conditions and can also provide the required energy of the load at the desired voltage level. The output voltage can be improved by utilizing magnetic coupling and a super voltage lift circuit (SLVC). The maximum voltage through the semiconductors can be decreased by using the SLVC technique. In addition, the suggested converter can draw continuous input current from two input DC supplies that lead to an increase in the lifetime of the input supplies. Besides, there is soft‐switching capability throughout the diodes, which leads to alleviate the reverse recovery losses and improve efficiency. To prove the performance of the suggested topology, the technical survey and mathematical analysis are carried out in the literature. A laboratory prototype with 20 and 12 V input DC supplies is prepared in this work to demonstrate the correctness of the recommenced converter operation.