bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dodecin as carrier protein for immunizations and bioengineering applications
Authors: Bourdeaux Florian , Kopp Yannick , Lautenschläger Julia , Gößner Ines , Besir Hüseyin , Vabulas R. Martin , Grininger Martin 
Published: March 2020

AbstractIn bioengineering, scaffold proteins have been increasingly used to recruit molecules to parts of a cell, or to enhance the efficacy of biosynthetic or signaling pathways. For example, scaffolds can be used to make weak or non-immunogenic small molecules immunogenic by attaching them to the scaffold, in this role called carrier. Here, we present the dodecin fromMycobacterium tuberculosis(mtDod) as a new scaffold protein.MtDod is a homododecameric complex of spherical shape, high stability and robust assembly, which allows the attachment of cargo at its surface. We show thatmtDod, either directly loaded with cargo or equipped with domains for non-covalent and covalent loading of cargo, can be produced recombinantly in high quantity and quality inEscherichia coli. Fusions ofmtDod with proteins of up to four times the size ofmtDod, e.g. with monomeric superfolder green fluorescent protein creating a 437 kDa large dodecamer, were successfully purified, showingmtDod’s ability to function as recruitment hub. Further,mtDod equipped with SYNZIP and SpyCatcher domains for post-translational recruitment of cargo was prepared of which themtDod/SpyCatcher system proved to be particularly useful. In a case study, we finally show thatmtDod peptide fusions allow producing antibodies against human heat shock proteins and the C-terminus of heat shock cognate 70 interacting protein (CHIP).For Table of Contents Only
Mating system modulates mate selection in aphidophagous ladybird,Menochilus sexmaculatus
Authors: Saxena Swati , Mishra Geetanjali , Omkar  
Published: March 2020

ABSTRACTMate competition and selection of mates is strongly influenced by the organism’s mating system. Monogamous matings provide more benefits as compared to polygamous matings. However, it has been proven that in polygamous systems, females gain benefits from the males, therefore indulging in multiple mating, leading males to access maximum females. In zigzag ladybird,Menochilus sexmaculatus, mate choice has been studied on several pre-and postcopulatory factors. However, mate choice as a function of mating system is still remains untouched. In the present study, we hypothesised that the mating system modulates mate selection of beetles. Adults were held in different mating systems and then males and females were tested in mate choice trials. Polygynous males were more preferred over monogynous males. However, males preferred monandrous females over polyandrous females. In a second experiment, we also included relatedness as additional factor. In female mate choice trials, females preferred unrelated monogynous males which were earlier rejected over related polygynous and in male mate choice trials, males preferred unrelated polyandrous females over related monandrous females. The results were not confined only to mate choice but significant effect was also observed on time to commence mating, copulation duration, fecundity and percent egg viability.
In vitroeffects on cellular shaping, contratility, cytoskeletal organization and mitochondrial activity in HL1 cells after different sounds stimulation. A qualitative pilot study and a theoretical physical model
Authors: Lin Carlo Dal , Radu Claudia Maria , Vitiello Giuseppe , Romano Paola , Polcari Albino , Iliceto Sabino , Simioni Paolo , Tona Francesco 
Published: March 2020

AbstractConvincing evidence has documented that mechanical vibrations profoundly affect the behaviour of different cell types and even the functions of different organs. Pressure waves such as those of sound could affect cytoskeletal molecules with coherent changes in their spatial organization and are conveyed to cellular nucleus via mechanotransduction. HL1 cells were grown and exposed to different sounds. Subsequently, cells were stained for phalloidin, beta-actin, alpha-tubulin, alpha-actinin-1 and MitoTracker®mitochondrial probe. The cells were analyzed with time-lapse and immunofluorescence/confocal microscopy. In this paper, we describe that different sound stimuli seem to influence the growth or death of HL1 cells, resulting in a different mitochondrial localization and expression of cytoskeletal proteins. Since the cellular behaviour seems to correlate with the meaning of the sound used, we speculate that it can be “understood” by the cells by virtue of the different sound waves geometric properties that we have photographed and filmed. A theoretical physical model is proposed to explain our preliminary results.
BK polyomavirus evades innate immune sensing by disrupting the mitochondrial network and membrane potential and by promoting mitophagy
Authors: Manzetti Julia , Weissbach Fabian H. , Unterstab Gunhild , Wernli Marion , Hopfer Helmut , Drachenberg Cinthia B. , Rinaldo Christine Hanssen , Hirsch Hans H. 
Published: March 2020

AbstractImmune escape contributes to viral persistence, yet little is known about human polyomaviruses. BK-polyomavirus (BKPyV) asymptomatically infects 90% of the human population, but causes early allograft failure in 10% of kidney transplants. Despite inducing potent virus-specific T-cells and neutralizing antibodies, BKPyV persists in the kidneys and regularly escapes from immune control as indicated by urinary shedding in immunocompetent individuals. Here, we report that BKPyV disrupts the mitochondrial network and its membrane potential when expressing the 66aa-long agnoprotein during late replication. Agnoprotein impairs nuclear IRF3-translocation, interferon-βexpression, and promotes p62-mitophagy in vitro and in kidney transplant biopsies. Agnoprotein-mutant viruses unable to disrupt mitochondria show reduced replication, which can be rescued by type-I-interferon-blockade, TBK1-inhibition, or CoCl2treatment. Agnoprotein is necessary and sufficient, using its amino-terminal and central domain for mitochondrial targeting and disruption, respectively. JCPyV- and SV40-infection similarly disrupt the mitochondrial network indicating a conserved mechanism facilitating polyomavirus persistence and post-transplant disease.
Calculation of fungal and bacterial inorganic nitrogen immobilization rates in soil
Authors: Li Xiaobo , He Hongbo , Zhang Xudong , Kazanci Caner , Li Zhian , Necpalova Magdalena , Ma Qianqian 
Published: March 2020

AbstractMicrobial inorganic nitrogen (N) immobilization is an important mechanism in the retention of N in soils. However, as a result of the high diversity and complexity of soil microorganisms, there is still no effective approach to measuring the respective immobilization rates of inorganic N by fungi and bacteria, which are the two dominant microbial communities in soils. We propose a mathematical framework, combining the experimentally measurable gross inorganic N immobilization rate and proxies for fungal and bacterial inorganic N immobilization rates, to quantify the respective immobilization rates of inorganic N by fungal and bacterial communities in soil. Our approach will help to unravel the mechanisms of N retention in soils.
Reward learning and working memory: effects of massed versus spaced training and post-learning delay period
Authors: Wimmer G. Elliott , Poldrack Russell A. 
Published: March 2020

AbstractNeuroscience research has illuminated the mechanisms supporting learning from reward feedback, demonstrating a critical role for the striatum and midbrain dopamine system. However, in humans, short-term working memory that is dependent on frontal and parietal cortices can also play an important role, particularly in commonly-used paradigms in which learning is relatively condensed in time. Given the growing use of reward-based learning tasks in translational studies in computational psychiatry, it is important to understand the degree of working memory contributions and whether gradual learning mechanisms can be better isolated. In our experiments, we manipulated the spacing between repetitions along with a post-learning delay preceding a test phase. We found that learning was slower for stimuli repeated after a long delay (spaced-trained) compared to those repeated immediately (massed-trained), likely reflecting the remaining contribution of feedback learning mechanisms when working memory is not available. Brief interruptions of massed learning led to drops in subsequent performance. Further, individual differences in working memory capacity positively correlated with massed learning performance. Critically, after a delay period but not immediately, relative preferences decayed in the massed condition and increased in the spaced condition. Overall, our results provide additional support for a large role of working memory in reward-based learning in temporally condensed designs. We suggest that spacing training within or between sessions is a promising approach to better isolate and understand mechanisms supporting gradual reward-based learning, with particular importance for understanding potential learning dysfunctions in addiction and psychiatric disorders.
Fine-mapping and QTL tissue-sharing information improve causal gene identification and transcriptome prediction performance
Authors: Barbeira Alvaro N. , Liang Yanyu , Bonazzola Rodrigo , Wang Gao , Wheeler Heather E. , Melia Owen J. , Aguet François ,   GTEx Consortiumt, Ardlie Kristin G , Wen Xiaoquan , Im Hae K. 
Published: March 2020

AbstractThe integration of transcriptomic studies and GWAS (genome-wide association studies) via imputed expression has seen extensive application in recent years, enabling the functional characterization and causal gene prioritization of GWAS loci. However, the techniques for imputing transcriptomic traits from DNA variation remain underdeveloped. Furthermore, associations found when linking eQTL studies to complex traits through methods like PrediXcan can lead to false positives due to linkage disequilibrium between distinct causal variants. Therefore, the best prediction performance models may not necessarily lead to more reliable causal gene discovery. With the goal of improving discoveries without increasing false positives, we develop and compare multiple transcriptomic imputation approaches using the most recent GTEx release of expression and splicing data on 17,382 RNA-sequencing samples from 948 post-mortem donors in 54 tissues. We find that informing prediction models with posterior causal probability from fine-mapping (dap-g) and borrowing information across tissues (mashr) lead to better performance in terms of number and proportion of significant associations that are colocalized and the proportion of silver standard genes identified as indicated by precision-recall and ROC (Receiver Operating Characteristic) curves. All prediction models are made publicly available atpredictdb.org.Author summaryIntegrating molecular biology information with genome-wide association studies (GWAS) sheds light on the mechanisms tying genetic variation to complex traits. However, associations found when linking eQTL studies to complex traits through methods like PrediXcan can lead to false positives due to linkage disequilibrium of distinct causal variants. By integrating fine-mapping information into the models, and leveraging the widespread tissue-sharing of eQTLs, we improve the proportion of likely causal genes among significant gene-trait associations, as well as the prediction of “ground truth” genes.
Transcriptome-wide profiles of circular RNA and RNA binding protein interactions reveal effects on circular RNA biogenesis and cancer pathway expression
Authors: Okholm Trine Line Hauge , Sathe Shashank , Park Samuel S. , Kamstrup Andreas Bjerregaard , Rasmussen Asta Mannstaedt , Shankar Archana , Fristrup Niels , Nielsen Morten Muhlig , Vang Søren , Dyrskjøt Lars , Aigner Stefan , Damgaard Christian Kroun , Yeo Gene , Pedersen Jakob Skou 
Published: March 2020

AbstractCircular RNAs (circRNAs) are stable, often highly expressed RNA transcripts with potential to modulate other regulatory RNAs. A few circRNAs have been shown to bind RNA binding proteins (RBPs), however, little is known about the prevalence and strength of these interactions in different biological contexts. Here, we comprehensively evaluate the interplay between circRNAs and RBPs in the ENCODE cell lines, HepG2 and K562, by profiling the expression of circRNAs in fractionated total RNA-sequencing samples and analyzing binding sites of 150 RBPs in large eCLIP data sets. We show that KHSRP binding sites are enriched in flanking introns of circRNAs in both HepG2 and K562 cells, and that KHSRP depletion affects circRNA biogenesis. Additionally, we show that exons forming circRNAs are generally enriched with RBP binding sites compared to non-circularizing exons. To detect individual circRNAs with regulatory potency, we computationally identify circRNAs that are highly covered by RBP binding sites and experimentally validate circRNA-RBP interactions by RNA immunoprecipitations. We characterize circCDYL, a highly expressed circRNA with clinical and functional implications in bladder cancer, which is covered with GRWD1 binding sites. We confirm that circCDYL binds GRWD1in vivoand functionally characterizes the effect of circCDYL-GRWD1 interactions on target genes in HepG2. Furthermore, we confirm interactions between circCDYL and RBPs in bladder cancer cells and demonstrate that circCDYL depletion affects hallmarks of cancer and perturbs the expression of key cancer genes, e.g.TP53andMYC. Finally, we show that elevated levels of highly RBP-covered circRNAs, including circCDYL, are associated with overall survival of bladder cancer patients. Our study demonstrates transcriptome-wide and cell-type-specific circRNA-RBP interactions that could play important regulatory roles in tumorigenesis.
In SilicoInvestigations on Curcuminoids fromCurcuma longaas Positive Regulators of Wnt/β-catenin Signaling Pathway in Wound Healing
Authors: Islam Reshad Riyan Al , Alam Sayka , Raihan Humaira Binte , Meem Kamrun Nahar , Rahman Fatima , Zahid Fardin , Rafid Md. Ikram , Rahman S. M. Obaydur , Omit Sadman , Ali Md. Hazrat 
Published: March 2020

AbstractCurcuma longa(Turmeric) is a traditionally used herb in wound healing. The efficacy of fresh Turmeric paste to heal wound has already been investigated in multiple ethnobotanical studies. Wnt/β-catenin signaling pathway plays a significant role in wound healing and injury repair processes which has been evident in differentin vitrostudies. This study aims to analyze the potentiality of Curcuminoids (Curcumin I, Curcumin II and Curcumin III) fromCurcuma longato bind and enhance the activity of two intracellular signaling proteins-Casein Kinase-1 (CK1) and Glycogen Synthase Kinase-3β (GSK3B) involved in Wnt/β-catenin signaling pathway. Present study is largely based on computer-based molecular docking program which mimics thein vivocondition and works on specific algorithm to interpret the binding affinity and poses of a ligand molecule to a receptor. Curcumin I showed better affinity of binding with CK1 (−10.31 Kcal/mol binding energy) and Curcumin II showed better binding affinity (−7.55 Kcal/mol binding energy) for GSK3B. Subsequently, Drug likeness property, ADME/Toxicity profile, Pharmacological activity and Site of metabolism of the Curcuminoids were also analyzed. All of the ligand molecules showed quite similar pharmacological properties.
Angiotensin II induces apoptosis in human induced pluripotent stem cell-derived cardiomyocytes
Authors: Gao Qiang , Wang Ping , Wu Zhiming , Qiu Hailong , Lin Bin , Chen Jimei , Cen Jianzheng , Zhuang Jian 
Published: March 2020

AbstractBackgroundThe renin-angiotensin system (RAS) functions fundamentally to regulate the pathological process of cardiovascular diseases, such as heart failure and hypertension. As the major effector in RAS, angiotensin II activates angiotensin II receptors to initiate the downstream pathways, which lead to the phenotypes including apoptosis, hypertrophy, and cardiac remodeling. Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) are being applied as a promising platform for personalized medicine to heart diseases. However, whether angiotensin II induces apoptosis in iPSC-CM is still obscure, which raises an uncertainty about the clinical applications of iPSC-CM.MethodsWe treated iPSC-CM with angiotensin II at eight concentrations (0 nM, 1 nM, 10 nM, 100 nM, 1 μM, 10 μM, 100 μM and 1 mM) and four incubation durations (24 hours, 48 hours, 6 days and 10 days), then PrestoBlue reagent and a apoptosis marker were used to examine the viability and apoptosis status of cardiomyocytes from each group. The expression levels of some apoptosis and proliferation related genes were also analyzed.ResultsHigh concentration angiotensin II with a long-term treatment caused apoptosis and cell viability drop-off in iPSC-CM. Specifically, under a 10-day treatment with 1 mM angiotensin II, the viability of iPSC-CM was reduced by an average of 41% (p=2.073E-08), and the percentage of apoptotic cells was 2.74 times higher than the controls averagely (p=6.248E-12). The data mining of previous RNA-seq data revealed that angiotensin II receptor type I was the major receptor in iPSC-CM. Conclusions: For the first time, our data confirmed the apoptotic effect of angiotensin II to iPSC-CM. The angiotensin II concentrations and exposure time for apoptosis induction were depicted in our study, which provided supports to iPSC-CM as anin vitromodel for cardiovascular disease study.
Population sequencing enhances understanding of tea plant evolution
Authors: Wang Xinchao , Feng Hu , Chang Yuxiao , Ma Chunlei , Wang Liyuan , Hao Xinyuan , Li A’lun , Cheng Hao , Wang Lu , Cui Peng , Jin Jiqiang , Wang Xiaobo , Wei Kang , Ai Cheng , Zhao Sheng , Wu Zhichao , Li Youyong , Liu Benying , Wang Guo-Dong , Chen Liang , Ruan Jue , Yang Yajun 
Published: March 2020

AbstractTea is an economically important plant characterized by a large genome size and high heterozygosity and species diversity. In this study, we assembled a 3.26 Gb high-quality chromosome-scale genome for tea using the ‘Longjing 43’ cultivar ofCamellia sinensisvar.sinensis. Population resequencing of 139 tea accessions from around the world was used to investigate the evolution of tea and to reveal the phylogenetic relationships among tea accessions. With the spread of tea cultivation, hybridization has increased the heterozygosity and wide-ranging gene flow among tea populations. Population genetics and transcriptomics analyses revealed that during domestication, the selection for disease resistance and flavor inC. sinensisvar.sinensispopulations has been stronger than that inC. sinensisvar.assamicapopulations. The data compiled in this study provide new resources for the marker assisted breeding of tea and are a basis for further research on the genetics and evolution of tea.
A displacement and velocity based dual model of saccadic eye movements best explains kinematic variability
Authors: Varsha V , Padhi Radhakant , Murthy Aditya 
Published: March 2020

Noise is a ubiquitous component of motor systems which leads to behavioral variability of all types of movements, including saccadic eye movements. Nonetheless, systems-based models of saccadic eye movements are deterministic and do not explain the observed saccade variability, only their central tendencies. Using stochastic models, we studied the variability in saccade behavior to test and distinguish between previously proposed deterministic saccade models. For this, the inter-trial variability in saccade displacement trajectories of human subjects was quantified while they performed repeated saccadic eye movements to a peripheral target. Based on fits to the data, we showed that existing models based on either displacement or velocity failed to capture the observed patterns in the variability of saccade trajectories. However, the observed behavior was captured by a dual control system, using a combination of displacement and velocity signal. The proposed model fits the mean displacement trajectory as well as the existing deterministic models. Taken together, our results suggest that the saccade system uses both desired displacement and velocity information.New and NoteworthyWe studied saccade behavior with a focus on the variability of the saccade trajectory. A stochastic model of the saccade system suggests that a dual control involving the control of displacement and velocity explains saccade behavior better than previously proposed models that utilize only displacement or velocity information. Our study resolves previous ambiguity regarding the use of displacement or velocity signals to guide saccades and provides a natural explanation for neural recordings that indicate multiplexing of displacement and velocity related information in the firing activity of neurons in the superior colliculus, a critical node in the oculomotor network that codes for saccadic eye movements.
Gonadulins, the fourth type of Insulin-related peptides in Decapods
Authors: Veenstra Jan A. 
Published: March 2020

AbstractInsulin and related peptides play important roles in the regulation of growth and reproduction. Until recently three different types of insulin-related peptides had been identified from decapod crustaceans. The identification of two novel insulin-related peptides fromSagmariasus verreauxiandCherax quadricarinatussuggested that there might a fourth type. Publicly available short read archives show that orthologs of these peptides are commonly present in these animals. Most decapods have two genes coding such peptides, butPenaeusspecies have likely only one and some palaemonids have three. Interestingly, expression levels can vary more than thousand-fold in the gonads ofPortunus trituberculatus, where gonadulin 1 is expressed by the testis and gonadulin 2 by the ovary. Although these peptides are also expressed in other tissues, the occasionally very high expression in the gonads led to them being called gonadulins.
Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C
Authors: Kent Alyssa , Vill Albert , Shi Qiaojuan , Satlin Michael J. , Brito Ilana Lauren 
Published: March 2020

AbstractThe gut microbiome harbors a ‘silent reservoir’ of antibiotic resistance (AR) genes that is thought to contribute to the emergence of multidrug-resistant pathogens through the process of horizontal gene transfer (HGT). To counteract the spread of AR genes, it is paramount to know which organisms harbor mobile AR genes and with which organisms they engage in HGT. Despite methods to characterize the bulk presence1, abundance2and function3of AR genes in the gut, technological limitations of short-read sequencing have precluded linking bacterial taxa to specific mobile genetic elements (MGEs) and their concomitant AR genes. Here, we apply and evaluate a high-throughput, culture-independent method for surveilling the bacterial carriage of MGEs, based on bacterial Hi-C protocols. We compare two healthy individuals with a cohort of seven neutropenic patients undergoing hematopoietic stem cell transplantation, who receive multiple courses of antibiotics throughout their prolonged hospitalizations, and are thus acutely vulnerable to the threat of multidrug-resistant infections4. We find that the networks of HGT are surprisingly distinct between individuals, yet AR and mobile genes are more dispersed across taxa within the neutropenic patients than the healthy subjects. Our data further suggest that HGT is occurring throughout the course of treatment in the microbiomes of neutropenic patients and within the guts of healthy individuals over a similar timeframe. Whereas most efforts to understand the spread of AR genes have focused on pathogenic species, our findings shed light on the role of the human gut microbiome in this process.