bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the appropriate oral lipid tolerance test model for investigating plasma triglyceride elevation in mice
Authors: Ochiai Masaru 
Published: June 2020

AbstractThe oral lipid tolerance test (OLTT) has been known to assess intestinal fat metabolism and whole-body lipid metabolism, but rodent models for OLTT are not yet established. Differences in OLTT methodology preclude the generation of definitive results, which may cause some confusion about the anti-hypertriglyceridemia effects of the test materials. To standardize and generate more appropriate methodology for the OLTT, we examined the effects of mice strain, dietary lipid sources, fasting period, and gender on lipid-induced hypertriglyceridemia in mice. First, lipid-induced hypertriglyceridemia was more strongly observed in male ddY mice than in C57BL/6N or ICR mice. Second, the administration of olive and soybean oils remarkably repressed lipid-induced hypertriglyceridemia in male ddY mice. Third, fasting period before the OLTT largely affected the plasma triglyceride elevation. Fasting for 12 h, but less than 48 h, provoked lipid-induced hypertriglyceridemia in male ddY mice. Fourth, we explored the suppressive effects of epigallocatechin gallate (EGCG), a green tea polyphenol, on lipid-induced hypertriglyceridemia. The administration of 100 mg/kg of EGCG suppressed lipid-induced hypertriglyceridemia and intestinal lipase activity in male ddY mice after 12 h fasting. Fifth, EGCG-induced suppressive effects were observed after lipid-induced hypertriglyceridemia was triggered in male mice. Lastly, lipid-induced hypertriglyceridemia could be more effectively induced in mice fed a high-fat diet for 1 week before the OLTT. These findings indicate that male ddY mice after 12 h fasting displayed marked lipid-induced hypertriglyceridemia in response to soybean oil and, hence, may be a more appropriate OLTT model.
ENSO drives lateral separation of FAD-associated skipjack and bigeye tuna in the Western Tropical Pacific
Authors: Leung Shirley , Mislan K. A. S. , Thompson LuAnne 
Published: June 2020

AbstractIncidental capture of juvenile bigeye tuna in fish aggregating device (FAD)-associated purse seine fisheries targeting skipjack tuna have contributed significantly to the degradation of bigeye stocks in the Western Tropical Pacific (WTP) Ocean. One way to reduce this incidental catch is to simply limit purse seine fishing effort; however, skipjack tuna stocks are healthy and economically important to many small island nations in the region. Here we assess whether there is sufficient lateral separation of skipjack and bigeye within FAD-associated purse seine fisheries in the WTP to allow limiting bigeye catch while maintaining a robust skipjack fishery. Based on monthly 5°-longitude-by-5°-latitude catch and effort data, FAD-associated bigeye and skipjack catch per unit effort (CPUE) covary tightly throughout the WTP, such that lateral separation between the two species is generally small. There are, however, significant variations in the amount of separation over both space and time. Waters within the Party to the Nauru Agreement exclusive economic zones (EEZs) belonging to Palau, Solomon Islands, and Tuvalu regularly exhibit some of the smallest bigeye-to-skipjack catch ratios, especially during El Niño. In contrast, waters within Kiribati’s Phoenix Islands EEZ regularly exhibit some of the largest bigeye-to-skipjack catch ratios, which are particularly high during La Niña. In general, El Niño lowers bigeye-to-skipjack catch ratios east of 170°E, while La Niña lowers bigeye-to-skipjack catch ratios west of 170°E. These ENSO-driven variations in separability are larger and more widespread than those driven by seasonality, due to larger associated variations in environmental conditions. Sea surface height anomalies may be particularly useful for demarcating the different environments preferred by skipjack and bigeye throughout the WTP. Sea surface temperatures, temperatures at 100 m, and thermocline depths may also help distinguish between the two species’ preferred habitats in many areas. These analyses can help better inform the complex decisions made by both fishers during operations and fisheries managers during creation of effective, dynamic policies to preserve bigeye stocks in the WTP. They also show that climate variability can have substantial effects on the spatial distributions of top pelagic predators and their interactions with one another.
The discovery of potential natural products for targeting SARS-CoV-2 spike protein by virtual screening
Authors: Chen Guan-Yu , Yao Tsung-You , Ahmed Azaj , Pan Yi-Cheng , Yang Juan-Cheng , Wu Yang-Chang 
Published: June 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters into the cells through its spike proteins binding to human angiotensin-converting enzyme 2 (ACE2) protein and causes virus infection in host cells. Until now, there are no available antiviral drugs have been reported that can effectively block virus infection. The study aimed to discover the potential compounds to prevent viral spike proteins to bind to the human ACE2 proteins from Taiwan Database of Extracts and Compounds (TDEC) by structure-based virtual screening. In this study, to rapidly discover potential inhibitors against SARS-CoV-2 spike proteins, the molecular docking calculation was performed by AutoDock Vina program. Herein, we found that 39 potential compounds may have good binding affinities and can respectively bind to the viral receptor-binding domain (RBD) of spike protein in the prefusion conformation and spike-ACE2 complex proteinin silico. Among those compounds, especially natural products thioflexibilolide A and candidine that were respectively isolated from the soft coralsSinularia flexibilisandPhaius mishmensismay have better binding affinity than others. This study provided the predictions that these compounds may have the potential to prevent SARS-CoV-2 spike protein from entry into cells.
Altered central pain processing in fibromyalgia – a multimodal neuroimaging case-control study using arterial spin labelling
Authors: Müller Monika , Wüthrich Florian , Federspiel Andrea , Wiest Roland , Egloff Niklaus , Reichenbach Stephan , Exadaktylos Aristomenis , Jüni Peter , Curatolo Michele , Walther Sebastian 
Published: June 2020

AbstractFibromyalgia is characterized by chronic pain and a striking discrepancy between objective signs of tissue damage and severity of pain. Function and structural alterations in brain areas involved in pain processing may explain this feature. Previous case-control studies in fibromyalgia focused on acute pain processing using experimentally-evoked pain paradigms. Yet, these studies do not allow conclusions about chronic, stimulus-independent pain. Resting-state cerebral blood flow (rsCBF) acquired by arterial spin labelling (ASL) may be a more accurate marker for chronic pain. The objective was to integrate four different functional and structural neuroimaging markers to evaluate the neural correlate of chronic, stimulus-independent pain using a resting-state paradigm. In line with the pathophysiological concept of enhanced central pain processing we hypothesized that rsCBF is increased in fibromyalgia in areas involved in processing of acute pain.We performed an age matched case-control study of 32 female fibromyalgia patients and 32 pain-free controls and calculated group-differences in rsCBF, resting state functional connectivity, grey matter density and cortical thickness using whole-brain and region of interest analyses. We adjusted all analyses for depression and anxiety. As centrally acting drugs are likely to interfere with neuroimaging markers, we performed a subgroup analysis limited to patients not taking such drugs.We found no differences between cases and control in rsCBF of the thalamus, the basal ganglia, the insula, the somatosensory cortex, the prefrontal cortex, the anterior cingulum and supplementary motor area as brain previously identified to be involved in acute processing in fibromyalgia. The results remained robust across all four neuroimaging markers and when limiting the study population to patients not taking centrally acting drugs and matched controls.In conclusion, we found no evidence for functional or structural alterations in brain areas involved in pain processing in fibromyalgia that could reflect neural correlates of chronic stimulus-independent pain.
Molecular Evolution of SARS-CoV-2 Structural Genes: Evidence of Positive Selection in Spike Glycoprotein
Authors: Zhan Xiao-Yong , Zhang Ying , Zhou Xuefu , Huang Ke , Qian Yichao , Leng Yang , Yan Leping , Huang Bihui , He Yulong 
Published: June 2020

AbstractSARS-CoV-2 caused a global pandemic in early 2020 and has resulted in more than 8,000,000 infections as well as 430,000 deaths in the world so far. Four structural proteins, envelope (E), membrane (M), nucleocapsid (N) and spike (S) glycoprotein, play a key role in controlling the entry into human cells and virion assembly of SARS-CoV-2. However, how these genes evolve during its human to human transmission is largely unknown. In this study, we screened and analyzed roughly 3090 SARS-CoV-2 isolates from GenBank database. The distribution of the four gene alleles is determined:16 for E, 40 for M, 131 for N and 173 for S genes. Phylogenetic analysis shows that global SARS-CoV-2 isolates can be clustered into three to four major clades based on the protein sequences of these genes. Intragenic recombination event isn’t detected among different alleles. However, purifying selection has conducted on the evolution of these genes. By analyzing full genomic sequences of these alleles using codon-substitution models (M8, M3 and M2a) and likelihood ratio tests (LRTs) of codeML package, it reveals that codon 614 of S glycoprotein has subjected to strong positive selection pressure and a persistent D614G mutation is identified. The definitive positive selection of D614G mutation is further confirmed by internal fixed effects likelihood (IFEL) and Evolutionary Fingerprinting methods implemented in Hyphy package. In addition, another potential positive selection site at codon 5 in the signal sequence of the S protein is also identified. The allele containing D614G mutation has undergone significant expansion during SARS-CoV-2 global pandemic, implying a better adaptability of isolates with the mutation. However, L5F allele expansion is relatively restricted. The D614G mutation is located at the subdomain 2 (SD2) of C-terminal portion (CTP) of the S1 subunit. Protein structural modeling shows that the D614G mutation may cause the disruption of salt bridge among S protein monomers increase their flexibility, and in turn promote receptor binding domain (RBD) opening, virus attachment and entry into host cells. Located at the signal sequence of S protein as it is, L5F mutation may facilitate the protein folding, assembly, and secretion of the virus. This is the first evidence of positive Darwinian selection in thespikegene of SARS-CoV-2, which contributes to a better understanding of the adaptive mechanism of this virus and help to provide insights for developing novel therapeutic approaches as well as effective vaccines by targeting on mutation sites.
The adaptive architecture is shaped by population ancestry and not by selection regime
Authors: Otte Kathrin A. , Nolte Viola , Mallard François , Schlötterer Christian 
Published: June 2020

AbstractUnderstanding the genetic architecture of adaptive phenotypes is a key question in evolutionary biology. One particularly promising approach is Evolve and Resequence (E&R), which combines advantages of experimental evolution such as time series, replicate populations and controlled environmental conditions, with whole genome sequencing. The recent analysis of replicate populations from two differentDrosophila simulansfounder populations, which were adapting to the same novel hot environment, uncovered very different architectures - either many selection targets with large heterogeneity among replicates or fewer selection targets with a consistent response among replicates. Here, we exposed the founder population from Portugal to a cold temperature regime. Although almost no selection targets were shared between the hot and cold selection regime, the adaptive architecture was similar: we identified a moderate number of loci under strong selection (19 selected alleles, mean selection coefficient = 0.072) and very parallel responses in the cold evolved replicates. This similarity across different environments indicates that the adaptive architecture depends more on the ancestry of the founder population than the specific selection regime. These observations have a pronounced impact on our understanding of adaptation in natural populations.
Cellular exocytosis gene (EXOC6/6B): a potential molecular link for the susceptibility and mortality of COVID-19 in diabetic patients
Authors: Hachim Mahmood Yaseen , Hachim Ibrahim Yaseen , Heialy Saba Al , Taneera Jalal , sulaiman Nabil 
Published: June 2020

AbstractDiabetes is one of the most critical comorbidities linked to an increased risk of severe complications in the current coronavirus disease 2019 (COVID-19) pandemic. A better molecular understanding of COVID-19 in people with type diabetes mellitus (T2D) is mandatory, especially in countries with a high rate of T2D, such as the United Arab Emirates (UAE). Identification of the cellular and molecular mechanisms that make T2D patients prone to aggressive course of the disease can help in the discovery of novel biomarkers and therapeutic targets to improve our response to the disease pandemic. Herein, we employed a system genetics approach to explore potential genomic, transcriptomic alterations in genes specific to lung and pancreas tissues, affected by SARS-CoV-2 infection, and study their association with susceptibility to T2D in Emirati patients. Our results identified the Exocyst complex component, 6 (EXOC6/6B) gene (a component for docks insulin granules to the plasma membrane) with documented INDEL in 3 of 4 whole genome sequenced Emirati diabetic patients. Publically available transcriptomic data showed that lung infected with SARS-CoV-2 showed significantly lower expression ofEXOC6/6Bcompared to healthy lungs.In conclusion, our data suggest thatEXOC6/6Bmight be an important molecular link between dysfunctional pancreatic islets and ciliated lung epithelium that makes diabetic patients more susceptible to severe SARS-COV-2 complication.
Characterization of the Novel Mitochondrial Genome Segregation Factor TAP110 inTrypanosoma brucei
Authors: Amodeo Simona , Kalichava Ana , Fradera-Sola Albert , Bertiaux-Lequoy Eloïse , Guichard Paul , Butter Falk , Ochsenreiter Torsten 
Published: June 2020

AbstractProper mitochondrial genome inheritance is key for eukaryotic cell survival, however little is known about the molecular mechanism controlling this process.Trypanosoma brucei, a protozoan parasite, contains a singular mitochondrial genome aka kinetoplast DNA (kDNA). kDNA segregation requires anchoring of the genome to the basal body via the tripartite attachment complex (TAC). Several components of the TAC as well as their assembly have been described, it however remains elusive how the TAC connects to the kDNA. Here, we characterize the TAC associated protein TAP110 and for the first time use ultrastructure expansion microscopy in trypanosomes to reveal that TAP110 is the currently most proximal kDNA segregation factor. The kDNA proximal positioning is also supported by RNAi depletion of TAC102, which leads to loss of TAP110 at the TAC. Overexpression of TAP110 leads to expression level changes of several mitochondrial proteins and a delay in the separation of the replicated kDNA networks. In contrast to other kDNA segregation factors TAP110 remains only partially attached to the flagellum after DNAse and detergent treatment and can only be solubilized in dyskinetoplastic cells, suggesting that interaction with the kDNA might be important for stability of the TAC association. Furthermore, we demonstrate that the TAC, but not the kDNA, is required for correct TAP110 localizationin vivoand suggest that TAP110 might interact with other proteins to form a >669 kDa complex.Summary StatementTAP110 is a novel mitochondrial genome segregation factor inTrypanosoma bruceithat associates with the previously described TAC component TAC102. Ultrastructure expansion microscopy reveals its proximal position to the kDNA.
CRISPR-finder: A high throughput and cost effective method for identifying successfully editedA. thalianaindividuals
Authors: Symeonidi Efthymia , Regalado Julian , Schwab Rebecca , Weigel Detlef 
Published: June 2020

AbstractBackgroundGenome editing with the CRISPR/Cas9 system allows the user to mutate a targeted region of the genome using an endonuclease (Cas9) and an artificial single-guide RNA (sgRNA). Both because of variable efficiency with which such mutations arise and because the repair process produces a spectrum of mutations, one needs to ascertain the genome sequence at the targeted locus for many individuals that have been subjected to CRISPR/Cas9 mutagenesis. This process can be laborious, expensive and inefficient with conventional methods such as the T7E1 assay or Sanger sequencing. An alternative comprises methods for amplicon sequencing, but most available protocols do not include a facile way for high throughput generation of the samples for sequencing.ResultsIn this study we provide a full pipeline based on amplicon sequencing, CRISPR-finder. We provide a complete protocol for the generation of amplicons up until the identification of the exact mutations in the targeted region. CRISPR-finder can be used to process thousands of individuals in a single sequencing run. For example, we were able to analyze in one sequencing reaction over 900Arabidopsis thalianaindividuals whose genomes had been targeted with the CRISPR/Cas9 system.ConclusionsIn order to validate the potential of CRISPR-finder, we targeted theISOCHORISMATE SYNTHASE 1gene inA. thalianausing the CRISPR/Cas9 system. We successfully identified a mutant line in which the production of salicylic acid was impaired compared to the wild type, as expected. These features establish CRISPR-finder as a high-throughput, cost-effective and -efficient genotyping method of individuals whose genomes have been targeted using the CRISPR/Cas9 system.
Generation of Heart Organoids Modeling Early Human Cardiac Development Under Defined Conditions
Authors: Israeli Yonatan , Gabalski Mitchell , Ball Kristen , Wasserman Aaron , Zou Jinyun , Ni Guangming , Zhou Chao , Aguirre Aitor 
Published: June 2020

AbstractCardiovascular-related disorders are a significant worldwide health problem. Cardiovascular disease (CVD) is the leading cause of death in developed countries, making up a third of the mortality rate in the US1. Congenital heart defects (CHD) affect ∼1% of all live births2, making it the most common birth defect in humans. Current technologies provide some insight into how these disorders originate but are limited in their ability to provide a complete overview of disease pathogenesis and progression due to their lack of physiological complexity. There is a pressing need to develop more faithful organ-like platforms recapitulating complexin vivophenotypes to study human development and diseasein vitro. Here, we report the most faithfulin vitroorganoid model of human cardiovascular development to date using human pluripotent stem cells (hPSCs). Our protocol is highly efficient, scalable, shows high reproducibility and is compatible with high-throughput approaches. Furthermore, our hPSC-based heart organoids (hHOs) showed very high similarity to human fetal hearts, both morphologically and in cell-type complexity. hHOs were differentiated using a two-step manipulation of Wnt signaling using chemical inhibitors and growth factors in completely defined media and culture conditions. Organoids were successfully derived from multiple independent hPSCs lines with very similar efficiency. hHOs started beating at ∼6 days, were mostly spherical and grew up to ∼1 mm in diameter by day 15 of differentiation. hHOs developed sophisticated, interconnected internal chambers and confocal analysis for cardiac markers revealed the presence of all major cardiac lineages, including cardiomyocytes (TNNT2+), epicardial cells (WT1+,TJP+), cardiac fibroblasts (THY1+,VIM+), endothelial cells (PECAM1+), and endocardial cells (NFATC1+). Morphologically, hHOs developed well-defined epicardial and adjacent myocardial regions and presented a distinct vascular plexus as well as endocardial-lined microchambers. RNA-seq time-course analysis of hHOs, monolayer differentiated iPSCs and fetal human hearts revealed that hHOs recapitulate human fetal heart tissue development better than previously described differentiation protocols3,4. hHOs allow higher-order interaction of distinct heart tissues for the first time and display biologically relevant physical and topographical 3D cues that closely resemble the human fetal heart. Our model constitutes a powerful novel tool for discovery and translational studies in human cardiac development and disease.
Increased Expression of Chondroitin Sulfotransferases following AngII may Contribute to Pathophysiology Underlying Covid-19 Respiratory Failure: Impact may be Exacerbated by Decline in Arylsulfatase B Activity
Authors: Bhattacharyya Sumit , Kotlo Kumar , Tobacman Joanne K. 
Published: June 2020

AbstractThe precise mechanisms by which Covid-19 infection leads to hypoxia and respiratory failure have not yet been elucidated. Interactions between sulfated glycosaminoglycans (GAGs) and the SARS-CoV-2 spike glycoprotein have been identified as participating in viral adherence and infectivity. The spike glycoprotein binds to respiratory epithelium through the angiotensin converting enzyme 2 (ACE2) receptor, which endogenously interacts with Angiotensin (Ang) II to yield Angiotensin 1-7. In this report, we show that stimulation of human vascular smooth muscle cells by Ang II leads to increased mRNA expression of two chondroitin sulfotransferases (CHST11 and CHST15), which are required for synthesis of chondroitin 4-sulfate (C4S) and chondroitin 4,6-disulfate (CSE), respectively. Also, increased total sulfated GAGs, increased sulfotransferase activity, and increased expression of the proteoglycans biglycan, syndecan, perlecan, and versican followed treatment by Ang II. Candesartan, an Angiotensin II receptor blocker (Arb), largely, but incompletely, inhibited these increases, and the differences from baseline remained significant. These results suggest that another effect of Ang II also contributes to the increased expression of chondroitin sulfotransferases, total sulfated GAGs, and proteoglycans. We hypothesize that activation of ACE2 may contribute to these increases and suggest that the SARS-CoV-2 spike glycoprotein interaction with ACE2 may also increase chondroitin sulfotransferases, sulfated GAGs, and proteoglycans and thereby contribute to viral adherence to bronchioalveolar cells and to respiratory compromise in SARS-CoV-2 infection.