bluuebunny/crossref_metadata_2025_split huggingface dataset:
Agonists of orally expressed TRP channels stimulate salivary secretion and modify the salivary proteome
Authors: Houghton Jack William , Carpenter Guy , Hans Joachim , Pesaro Manuel , Lynham Steven , Proctor Gordon 
Published: June 2020

AbstractNatural compounds that can stimulate salivary secretion are of interest in developing treatments for xerostomia, the perception of a dry mouth, that affects between 10 and 30% of the adult and elderly population. Chemesthetic transient receptor potential (TRP) channels are expressed in the surface of the oral mucosa. The TRPV1 agonists capsaicin and piperine have been shown to increase salivary flow when introduced into the oral cavity but the sialogogic properties of other TRP channel agonists have not been investigated. In this study we have determined the influence of different TRP channel agonists on the flow and protein composition of saliva.Mouth rinsing with the TRPV1 agonist nonivamide or menthol, a TRPM8 agonist, increased whole mouth saliva (WMS) flow and total protein secretion compared to unstimulated saliva, the vehicle control mouth rinse or cinnamaldehyde, a TRPA1 agonist. Nonivamide also increased the flow of labial minor gland saliva but parotid saliva flow rate was not increased. The influence of TRP channel agonists on the composition and function of the salivary proteome was investigated using a multi-batch quantitative mass spectrometry method novel to salivary proteomics. Inter-personal and inter-mouth rinse variation was observed in the secreted proteomes and, using a novel bioinformatics method, inter-day variation was identified with some of the mouth rinses. Significant changes in specific salivary proteins were identified after all mouth rinses. In the case of nonivamide, these changes were attributed to functional shifts in the WMS secreted, primarily the over representation of salivary and non-salivary cystatins which was confirmed by immunoassay.This study provides new evidence of the impact of TRP channel agonists on the salivary proteome and the stimulation of salivary secretion by a TRPM8 channel agonist, which suggests that TRP channel agonists are potential candidates for developing treatments for sufferers of xerostomia.
Molecular determinants of MED1 interaction with the DNA bound VDR-RXR heterodimer
Authors: Belorusova Anna Y. , Bourguet Maxime , Hessmann Steve , Chalhoub Sandra , Kieffer Bruno , Cianférani Sarah , Rochel Natacha 
Published: June 2020

AbstractThe MED1 subunit of the Mediator complex is an essential coactivator of nuclear receptor-mediated transcriptional activation. While structural requirements for ligand-dependent binding of classical coactivator motifs of MED1 to numerous nuclear receptor ligand-binding domains have been fully elucidated, the recognition of the full-length or truncated coactivator by full nuclear receptor complexes remain unknown. Here we present structural details of the interaction between a large part of MED1 comprising its structured N-terminal and the flexible receptor-interacting domains and the mutual heterodimer of the vitamin D receptor (VDR) and the retinoid X receptor (RXR) bound to their cognate DNA response element. Using a combination of structural and biophysical methods we show that the ligand-dependent interaction between VDR and the second coactivator motif of MED1 is crucial for complex formation and we identify additional, previously unseen, interaction details. In particular, we identified RXR regions involved in the interaction with structured N-terminal domain of MED1, as well as VDR regions outside the classical coactivator binding cleft affected by coactivator recruitment. These findings highlight important roles of each receptor within the heterodimer in selective recognition of MED1 and contribute to our understanding of the nuclear receptor-coregulator complexes.
A new (old) approach to genotype-based phylogenomic inference within species, with an example from the saguaro cactus (Carnegiea gigantea)
Authors: Sanderson Michael J. , Búrquez Alberto , Copetti Dario , McMahon Michelle M. , Zeng Yichao , Wojciechowski Martin F. 
Published: June 2020

AbstractGenome sequence data are routinely being used to infer phylogenetic history within and between closely related diploid species, but few tree inference methods are specifically tailored to diploid genotype data. Here we re-examine the method of “polymorphism parsimony” (Inger 1967; Farris 1978; Felsenstein 1979), originally introduced to study morphological characters and chromosome inversion polymorphisms, to evaluate its utility for unphased diploid genotype data in large scale phylogenomic data sets. We show that it is equivalent to inferring species trees by minimizing deep coalescences—assuming an infinite sites model. Two potential advantages of this approach are scalability and estimation of a rooted tree. As with some other single nucleotide polymorphism (SNP) based methods, it requires thinning of data sets to statistically independent sites, and we describe a genotype-based test for phylogenetic independence. To evaluate this approach in genome scale data, we construct intraspecific phylogenies for 10 populations of the saguaro cactus using 200 Gbp of resequencing data, and then use these methods to test whether the population with highest genetic diversity corresponds to the root of the genotype trees. Results were highly congruent with the (unrooted) trees obtained using SVDquartets, a scalable alternative method of phylogenomic inference.
Genome ofSolanum pimpinellifoliumprovides insights into structural variants during tomato breeding
Authors: Wang Xin , Gao Lei , Jiao Chen , Stravoravdis Stefanos , Hosmani Prashant S. , Saha Surya , Zhang Jing , Mainiero Samantha , Strickler Susan R. , Catala Carmen , Martin Gregory B. , Mueller Lukas A. , Vrebalov Julia , Giovannoni James J. , Wu Shan , Fei Zhangjun 
Published: June 2020

AbstractSolanum pimpinellifolium(SP) is the wild progenitor of cultivated tomato. Because of its remarkable stress tolerance and intense flavor, SP has been used as an important germplasm donor in modern breeding of tomato. Here we present a high-quality chromosome-scale genome sequence of SP LA2093. Genome comparison identifies more than 92,000 high-confidence structural variants (SVs) between LA2093 and the modern cultivar, Heinz 1706. Genotyping these SVs in ~600 representative tomato accessions unravels alleles under selection during tomato domestication, improvement and modern breeding, and discovers numerous novel SVs underlying genes known to regulate important breeding traits such as fruit weight and lycopene content. Expression quantitative trait locus (eQTL) analysis detects hotspots harboring master regulators controlling important fruit quality traits, including cuticular wax accumulation and flavonoid biosynthesis, and novel SVs contributing to these complex regulatory networks. The LA2093 genome sequence and the identified SVs provide rich resources for future research and biodiversity-based breeding.
Sorghum bicolorcultivars have divergent and dynamic gene regulatory networks that control the temporal expression of genes in stem tissue
Authors: Arachchilage Madara Hetti , Mullet John E. , Marshall-Colon Amy 
Published: June 2020

AbstractThe genetic engineering of value-added traits such as the accumulation of bioproducts in high biomass C4 grass stems is one promising strategy to make plant-derived biofuels more economical for industrial use. A first step toward achieving this goal is to identify stem-specific promoters that can drive the expression of genes of interest with good temporal and spatial specificity. However, a comprehensive characterization of the spatial-temporal regulatory elements of stem tissue-specific promoters for C4 grasses has not been reported. Therefore, we performed anin-silicoanalysis onSorghum bicolor cv BTx623transcriptomes from multiple tissues over development to identify stem-expressed genes. The analysis identified 10 genes that are “Always-On-Stem-Specific,” 59 genes that are “Temporally-Stem-Specific during early development,” and 21 genes that are “Temporally-Stem-Specific during late development.” Promoter analysis revealed common and/or unique cis-regulatory elements in promoters of genes within each of the three categories. Subsequent gene regulatory network (GRN) analysis revealed that different transcriptional regulatory programs are responsible for the temporal activation of the stem-expressed genes. The analysis of temporal stem GRNs between sweet (cv Della) and grain (cv BTx623) sorghum varieties revealed genetic variation that could influence the regulatory landscape. This study provides new insights about sorghum stem biology, and information for future genetic engineering efforts to fine-tune the spatial-temporal expression of transgenes in C4 grass stems.
Extracellular matrix protein composition dynamically changes during murine forelimb development
Authors: Jacobson Kathryn R. , Saleh Aya M. , Lipp Sarah N. , Ocken Alexander R. , Kinzer-Ursem Tamara L. , Calve Sarah 
Published: June 2020

SummaryThe extracellular matrix (ECM) is an integral part of multicellular organisms, connecting different cell layers and tissue types. During morphogenesis and growth, tissues undergo substantial reorganization involving cellular proliferation, migration, and differentiation. While it is intuitive that the ECM remodels in concert, little is known regarding how matrix composition and organization change during development. We utilized tissue fractionation and mass spectrometry to define ECM protein (matrisome) dynamics during murine forelimb development and resolved significant differences in ECM composition as a function of development, disease and tissue type. Additionally, we used bioorthogonal non-canonical amino acid tagging (BONCAT) to label newly synthesized ECM within the developing forelimb. We demonstrate the feasibility of using BONCAT to enrich for newly synthesized matrisome components and identified differences in ECM synthesis between morphogenesis and growth. This resource will guide future research investigating the role of the matrisome during complex tissue development.
Ten Genetic Loci Identified for Milk Yield, Fat, and Protein in Holstein Cattle
Authors: Liu Liyuan , Zhou Jinghang , Chen Chunpeng James , Zhang Juan , Wen Wan , Tian Jia , Zhang Zhiwu , Gu Yaling 
Published: June 2020

AbstractHigh-yield and high-quality of milk are the primary goals of dairy production. Understanding the genetic architecture underlying these milk production traits is beneficial so that genetic variants can be targeted toward the genetic improvement. In this study, we measured five milk production traits in Holstein cattle population from China. These traits included milk yield, protein yield, fat yields; fat percentage and protein percentages. We used the estimated breeding values as dependent variables to conduct the genome-wide association studies (GWAS). Breeding values were estimated through pedigree relationships by using a mixed linear model for individuals with and without phenotypic data. Genotyping was carried out on the individuals with phenotypes by using the Illumina BovineSNP150 BeadChip. The association analyses were conducted by using the Fixed and random model Circulating Probability Unification (FarmCPU) method. A total of ten SNPs was detected above the genome-wide significant threshold, including six located in previously reported QTL regions. We found eight candidate genes within distances of 120 kb upstream or downstream to the associated SNPs. The most significant SNP is onDGAT1gene affecting milk fat and protein percentage. These genetic variants and candidate genes would be valuable resources to enhance dairy cattle breeding.
Neural correlates of temporal presentness in the precuneus: a crosslinguistic fMRI study based on speech stimuli
Authors: Tang Long , Takahashi Toshimitsu , Shimada Tamami , Komachi Masayuki , Imanishi Noriko , Nishiyama Yuji , Iida Takashi , Otsu Yukio , Kitazawa Shigeru 
Published: June 2020

AbstractsThe position of any event in time could be either present, past, or future. This temporal discrimination is vitally important in our daily conversations, but it remains elusive how the human brain distinguishes among the past, present, and future. To address this issue, we searched for neural correlates of presentness, pastness, and futurity, each of which is automatically evoked when we hear sentences such as ‘it is raining now’, ‘it rained yesterday’, or ‘it will rain tomorrow’. Here, we show that sentences that evoked ‘presentness’ activated the bilateral precuneus more strongly than those that evoked ‘pastness’ or ‘futurity’. Interestingly, this contrast was shared across native speakers of Japanese, English, and Chinese, languages which vary considerably in their verb tense systems. The results suggest that the precuneus serves as a key region that provides the origin, the Now, to our time perception irrespective of differences in tense systems across languages.
Molecular mode of action of an Acyl Protein thioesterase
Authors: Abrami Laurence , Audagnotto Martina , Ho Sylvia , Marcaida Maria Jose , Mesquita Francisco S. , Anwar Muhammad U. , Sandoz Patrick A. , Fonti Giulia , Pojer Florence , Peraro Matteo Dal , van der Goot F. Gisou 
Published: June 2020

ABSTRACTMany biochemical reactions occur at the membrane interfaces. The proper control of these reactions requires spatially and temporally controlled recruitment of protein complexes. These assemblies are largely regulated by post-translational modifications and a frequent one is S-acylation, which consists of the addition of medium length acyl chains. Reversibility of this modification is ensured by acyl protein thioesterases (APTs), which are poorly understood enzymes. Using a combination of computational, structural, biochemical, and cellular approaches, we dissect the mode of action of a major cellular thioesterase, APT2 (LYPLA2). We show that for APT2 to encounter its targets, it must interact with membranes by two consecutive steps, the insertion of a hydrophobic loop and subsequent S-acylation by the ZDHHC3 or ZDHHC7 palmitoyltransferases. Once bound, APT2 deforms the lipid bilayer to extract the acyl chain bound to its substrate, capturing it in a hydrophobic pocket and allowing hydrolysis. Deacylation releases APT2, allowing it to bind to other membranes, but also renders it vulnerable to ubiquitination and proteasomal degradation. This molecular understanding of APT2 paves the way to understand the dynamics of APT2-mediated depalmitoylation throughout the endomembrane system.
Comparison of human and mouse fetal intestinal tissues reveals differential maturation timelines
Authors: Lim A.A. , Nadkarni R.R. , Courteau B.C. , Draper J.S. 
Published: June 2020

AbstractMaturation of the intestinal epithelium is a necessary step for development of a fully functioning gastrointestinal tract. Studies of rodent gastrointestinal development and maturation have long been used to guide understanding of human intestinal maturation, in part because accessing human gestational stage intestinal tissues to perform equivalent human studies can be difficult. Notable differences have already been described in the timing of key stages in intestinal development between rodents and humans, but the conservation of intestinal maturation events between the two species is poorly understood. We hypothesized that species-related differences in intestinal development would alter the timing of key maturation events between human and mouse. We tested our hypothesis by performing a detailed comparison of hallmarks of intestinal maturation in human and mouse gestational intestine, including markers that describe the emergence of intestinal cell types, functionality and structural integrity. Our study demonstrates clear timing differences between maturation stages in mouse and human, with the majority of human maturation hallmarks acquired post-partum, in contrast to their gestational emergence in mouse. Our work suggests caution when translating murine intestinal maturation observations to the human, and provides a maturation road map that will be helpful to those seeking to produce mature intestine fromin vitrostem cell sources.
Bcr-Abl tyrosine kinase inhibitor imatinib as a potential drug for COVID-19
Authors: Mulgaonkar Nirmitee , Wang Haoqi , Mallawarachchi Samavath , Fernando Sandun , Martina Byron , Ruzek Daniel 
Published: June 2020

AbstractThe rapid geographic expansion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent of Coronavirus Disease 2019 (COVID-19) pandemic, poses an immediate need for potent drugs. Enveloped viruses infect the host cell by cellular membrane fusion, a crucial mechanism required for virus replication. The SARS-CoV-2 spike glycoprotein, due to its primary interaction with the human angiotensin-converting enzyme 2 (ACE2) cell-surface receptor, is considered as a potential target for drug development. Based onin silicoscreening followed byin vitrostudies, here we report that the existing FDA-approved Bcr-Abl tyrosine kinase inhibitor, imatinib, inhibits SARS-CoV-2 with an IC50of 130 nM. We provide evidence that although imatinib binds to the receptor-binding domain (RBD) of SARS-CoV-2 spike protein with an affinity at micromolar, i.e., 2.32 ± 0.9 μM levels, imatinib does not directly inhibit the spike RBD:ACE2 interaction – suggesting a Bcr-Abl kinase-mediated fusion inhibition mechanism is responsible for the inhibitory action. We also show that imatinib inhibits other coronaviruses, SARS-CoV, and MERS-CoV via fusion inhibition. Based on promisingin vitroresults, we propose the Abl tyrosine kinase inhibitor (ATKI), imatinib, to be a viable repurposable drug against COVID-19.
Accessory ESCRT-III proteins selectively regulate Rab11-exosome biogenesis inDrosophilasecondary cells
Authors: Marie Pauline P. , Fan Shih-Jung , Mendes Claudia C. , Wainwright S. Mark , Harris Adrian L. , Goberdhan Deborah C. I. , Wilson Clive 
Published: June 2020

AbstractExosomes are secreted nanovesicles with potent signalling activity that are initially formed as intraluminal vesicles (ILVs) in multivesicular endosomes, which subsequently fuse with the plasma membrane. These ILVs are made in both late endosomes and recycling endosomes, the latter marked by the small GTPase Rab11 and generating exosomes with different cargos and functions. Core proteins within four Endosomal Sorting Complex Required for Transport (ESCRT) assemblies (0-III) play key sequential roles in late endosomal exosome biogenesis and ILV-mediated destruction of ubiquitinylated cargos through the endolysosomal system. They also control additional cellular processes, such as cytokinesis and other vesicle budding. By contrast, the functions of several accessory ESCRTs are not well defined. Here we assess the ESCRT-dependency of Rab11-exosomes, using RNA knockdown inDrosophilasecondary cells (SCs) of the male accessory gland, which have unusually enlarged Rab11-positive compartments. Unexpectedly, not only are core proteins in all four ESCRT complexes required for Rab11-exosome formation, but also accessory ESCRT-III proteins, CHMP1, CHMP5 and IST1. Suppressing expression of these accessory proteins does not affect other aspects of cell morphology, unlike most core ESCRT knockdowns, and does not lead to accumulation of ubiquitinylated cargos. We conclude that accessory ESCRT-III components have a specific and potentially ubiquitin-independent role in Rab11-exosome generation, which might provide a target for blocking the pro-tumorigenic activities of these vesicles in cancer.
Optimized residue analysis method for broflanilide and its metabolites in agricultural produce using the QuEChERS method and LC-MS/MS
Authors: Noh Hyun Ho , Kim Chang Jo , Kwon Hyeyoung , Kim Danbi , Moon Byeong-chul , Baek Sujin , Oh Min-seok , Kyung Kee Sung 
Published: June 2020

AbstractSince broflanilide is a newly developed pesticide, analytical methods are required to determine the corresponding pesticide residues in diverse crops and foods. In this study, a pesticide residue analysis method was optimized for the detection and quantification of broflanilide and its two metabolites, DM-8007 and S(PFH-OH)-8007, in brown rice, soybean, apple, green pepper, mandarin, and kimchi cabbage. Residue samples were extracted from the produce using QuEChERS acetate and citrate buffering methods and were purified by dispersive solid-phase extraction (d-SPE) using six different adsorbent compositions with varying amounts of primary secondary amine (PSA), C18, and graphitized carbon black. All the sample preparation methods gave low-to-medium matrix effects, as confirmed by liquid chromatography–tandem mass spectrometry using standard solutions and matrix-matched standards. In particular, the use of the citrate buffering method, in combination with purification by d-SPE using 25 mg of PSA and a mixture of other adsorbents, consistently gave low matrix effects that in the range from −18.3 to 18.8%. Pesticide recoveries within the valid recovery range 70–120% were obtained both with and without d-SPE purification using 25 mg of PSA and other adsorbents. Thus, the developed residue analysis method is viable for the determination of broflanilide and its metabolites in various crops.