bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systems and classical biology approaches unraveled role of olfactory receptors in progression of kidney fibrosis
Authors: Motahharynia Ali , Moein Shiva , Kiyanpour Farnoush , Moradzadeh Kobra , Gheisari Yousof 
Published: July 2020

AbstractThe olfactory receptors (ORs) which are mainly known as odor-sensors in the olfactory epithelium are distributed in several non-sensory tissues. Despite the specified role of some of these receptors in normal physiology of the kidney, little is known about their potential effect in renal disorders. In this study, using the holistic view of systems biology, it was determined that ORs are significantly changed during the progression of kidney fibrosis. For further validation, common differentially expressed ORs resulted from reanalysis of two time-course microarray datasets were selected for experimental evaluation in a validated murine model of unilateral ureteral obstruction. Transcriptional analysis demonstrated considerable changes in the expression pattern ofOlfr433, Olfr129, Olfr1393, and Olfr161during the progression of kidney fibrosis. In conclusion, our results highlight the impact of systems biology in determination of the underlying mechanisms of chronic diseases and indicate the importance of time-course approaches to unravel the patterns of gene expression. The novel ORs proposed in this study could be the subject of further functional investigations in the kidney.
Virtual Screening and Elucidation of Putative Binding Mode for Small Molecule Antagonist of BCL2 BH4 Domain
Authors: Joel Ireoluwa Yinka , Adigun Temidayo Olamide , Ajibola Ahmeedah Ololade , Bankole Olukayode Olusola , Ozojiofor Ugochukwu Okechukwu , Remi-Esan Ifelolu Adeseye , Sulaimon Lateef Adegboyega 
Published: July 2020

AbstractEvading apoptosis is a hallmark of cancer cells, therefore therapeutic strategies have been developed to induce cell death. BCL2 family protein governs the intrinsic pathway of cell death. Targeting the BH4 domain to modulate the anti-apoptosis activities of BCL2 protein has been established however, BDA366 is the only BH4 binding molecule to be reported. Virtually screening ~ 1,000,000 compounds 11 putative BH4 binding small molecules with binding affinity ~ −84kcal/mol to - 64kcal/mol resulted. Using QM-polarized docking, Induced-fit docking, and QM-MM optimization, a putative binding mode for the top 3 compounds is proposed: compound 139068 interactions with GLU13, MET16, LYS17, ASP31, and GLU42; compound 138967 interactions with ASP10, ARG12, GLU13, HIS20, MET16, and GLU42; compound 38831 interactions with ASP10, ARG12, GLU13, LYS17, and GLU42. MD simulations (NMA) data showed the binding of the three compounds to be stable with low eigenvalues. Electronic properties derived via DFT calculations suggest chemical reaction of the compounds be via electrophilic reactions.
Genetic Algorithms as a method to study adaptive walks in biological landscapes
Authors: Invernizzi Edith , Ruxton Graeme D 
Published: July 2020

AbstractThe metaphor of fitness landscapes is common in evolutionary biology, as a way to visualise the change in allele or phenotypic frequencies of a population under selection. Understanding how different factors in the evolutionary process affect the trajectory of the population across the landscape is of interest to both theoretical and empirical evolutionary biologists. However, fitness landscape studies often have to rely heavily on mathematical methods that are not easy to access by biologically trained researchers. Here, we used a method borrowed from engineering - genetic algorithms - to simulate the evolutionary process and study how different components affect the path taken through a phenotypic fitness landscape. In a simple study, we compare five selection models that reflect different degrees of dependency of fitness on trait quality: this includes strengths of selection, trait-quality dependent reproductive hierarchy and the amount of stochasticity in the reproductive process. We include an analysis of other evolutionary variables such as population size and mutation rate. We analyse a game theory problem, as a test landscape, that lends itself to analysis through a deterministic mathematical simulation, which we use for comparison. Our results show that there are differences in the speed with which different models of selection lead to the fitness optimum.Author summaryEvolution and adaptation in biology occurs infitness landscapes, multidimensional spaces representing all possible genotypic or phenotypic combinations, where population adapt by following the cline of the fitness dimension. The study of adaptation on complex fitness landscapes has so far been limited by the need for mathematically heavy methods. Here, we present a simulation modelling framework, genetic algorithms, that can be used for evolutionary simulations of a population on a fitness landscape of chosen features and with custom evolutionary parameters.
Regulatory T cell activation triggers specific changes in glycosylation associated with Siglec-1-dependent inflammatory responses
Authors: Wu Gang , Murugesan Gavuthami , Nagala Manjula , McCraw Alex , Haslam Stuart M. , Dell Anne , Crocker Paul R. 
Published: July 2020

AbstractSiglec-1 is a macrophage lectin-like receptor that mediates sialic acid-dependent cellular interactions. It was shown previously to promote inflammation in autoimmune disease through suppressing the expansion of regulatory T cells (Tregs). We have investigated the molecular basis for Siglec-1 binding to these cells usingin vitro-induced Tregs. Siglec-1 binding was strongly upregulated on activated cells, but lost under resting conditions. Glycosylation changes that affect Siglec-1 binding were studied by comparing activated and resting Tregs using RNA-Seq, glycomics, proteomics and binding of selected antibodies and lectins. A proximity labelling and proteomics strategy identified 49 glycoproteins expressed by activated Tregs that may function as Siglec-1 counter-receptors. These represent ∼5% of the total membrane protein pool and were mainly related to T cell activation and proliferation. We demonstrate that several of these counter-receptors are upregulated following activation of Tregs and provide initial evidence that their altered glycosylation may also be important for Siglec-1 binding.
Repression ofPdzrn3is required for heart maturation and protects against heart failure
Authors: Pernot Mathieu , Jaspard-vinassa Béatrice , Abelanet Alice , Rubin Sebastien , Forfar Isabelle , Jeanningros Sylvie , Cetran Laura , Yu Murielle Han-Yee , Balse Elise , Hatem Stéphane , Dufourcq Pascale , Couffinhal Thierry , Duplàa Cécile 
Published: July 2020

AbstractHeart failure is the final common stage of most cardiopathies. Cardiomyocytes connect with others via their extremities by intercalated disk protein complexes. This planar and directional organization of myocytes is crucial for mechanical coupling and anisotropic conduction of the electric signal in the heart. One of the hallmarks of heart failure is alterations in the contact sites between cardiomyocytes. Yet no factor on its own is known to coordinate cardiomyocyte polarized organization. We report enhanced levels of an ubiquitine ligasePdzrn3in diseased hypertrophic human and mouse myocardium, which correlates with a loss of cardiomyocyte polarized elongation. We provide evidence thatPdzrn3has a causative role in heart failure. We found that cardiacPdzrn3deficiency protected against heart failure while over expression ofPdzrn3in mouse cardiomyocytes during the first weeks of life, impaired postnatal cardiomyocyte maturation leading to premature death. Our results reveal a novel signaling pathway that controls a genetic program essential for heart maturation and maintenance of overall geometry, as well as the contractile function of cardiomyocytes, and implicates PDZRN3 as a potential therapeutic target for the prevention of human heart failure.
Origins, History and Molecular Characterization of Creole Cane
Authors: Evans Dyfed Lloyd , Joshi Shailesh Vinay 
Published: July 2020

AbstractSince it was first introduced to Europe in 711 CE and planted in the Americas in 1506, a single type of cane dominated sugar production for 1100 years, until it was finally ousted by Tahitian cane c. 1790. This cane became known as ‘CreoleâĂŹ and is present in the ancestry of many sugarcane hybrids, even today. Whether there was only a single variety of Creole cane or multiple varieties has been a matter of debate for decades. Creole cane remains relevant today, as a Creole cane from Jamaica is the currently chosen lecotype for Saccharum officinarum. In this study we identify 18 historical images of Creole cane, many not previously published. We employ image analyses to characterize the internodes and demonstrate evidence for only a single type of Creole in the new world. Chloroplasts and 45s ribosomal RNA sequences from the cultivar BH10/12 (known to have a Creole female parent) were determined that Java ribbon cane is the historical New World sugarcane known as Creole. We demonstrate that Creole cane is an hybrid and not a single species. ThusS. officinarumhas no type specimen. We also sequence a ribbon cane (also known as Guinguam) that appeared in the Caribbean between 1790 and 1810 and demonstrate that this cane was a Sinense type from Java that links back to the work of Rumphinus (1660s).
Viscoelastic properties of wheat gluten in a molecular dynamics study
Authors: Mioduszewski Łukasz , Cieplak Marek 
Published: July 2020

AbstractWheat(Triticum spp.) gluten consists mainly of intrinsincally disordered storage proteins (glutenins and gliadins) that can form megadalton-sized networks. These networks are responsible for the unique viscoelastic properties of wheat dough and affect the quality of bread. These properties have not yet been studied by molecular level simulations. Here, we use a newly developedα-C-based coarse-grained model to study ∼ 4000-residue systems. The corresponding time-dependent properties are studied through shear and axial deformations. We measure the response force to the deformation, the number of entanglements and cavities, the size of fluctuations, the number of the inter-chain bonds, etc. Glutenins are shown to influence the mechanics of gluten much more than gliadins. Our simulations are consistent with the existing ideas about gluten elasticity and emphasize the role of entanglements and hydrogen bonding. We also demonstrate that the storage proteins in maize and rice lead to weaker elasticity which points to the unique properties of wheat gluten.
Precisely-timed dopamine signals establish distinct kinematic representations of skilled movements
Authors: Bova Alexandra , Gaidica Matt , Hurst Amy , Iwai Yoshiko , Leventhal Daniel K. 
Published: July 2020

AbstractBrain dopamine is critical for normal motor control, as evidenced by its importance in Parkinson Disease and related disorders. Current hypotheses are that dopamine influences motor control by “invigorating” movements and regulating motor learning. Most evidence for these aspects of dopamine function comes from simple tasks (e.g., lever pressing). Therefore, the influence of dopamine on motor skills requiring multi-joint coordination is unknown. To determine the effects of precisely-timed dopamine manipulations on the performance of a complex, finely coordinated dexterous skill, we optogenetically stimulated or inhibited midbrain dopamine neurons as rats performed a skilled reaching task. We found that reach kinematics and coordination between gross and fine movements progressively changed with repeated manipulations. However, once established, rats transitioned abruptly between aberrant and baseline reach kinematics in a dopamine-dependent manner. These results suggest that precisely-timed dopamine signals have immediate and long-term influences on motor skill performance, distinct from simply “invigorating” movement.
PdgfraandPdgfrbgenetically interact in the murine neural crest cell lineage to regulate migration and proliferation
Authors: Mo Julia , Long Robert , Fantauzzo Katherine A. 
Published: July 2020

AbstractCranial neural crest cells (cNCCs) are migratory, multipotent cells that originate from the forebrain to the hindbrain and eventually give rise to the bone and cartilage of the frontonasal skeleton, among other derivatives. Signaling through the two members of the platelet-derived growth factor receptor (PDGFR) family of receptor tyrosine kinases, alpha and beta, plays critical roles in the cNCC lineage to regulate craniofacial development during murine embryogenesis. Further, the PDGFRs have been shown to genetically interact during murine craniofacial development at mid-to-late gestation. Here, we examined the effect of ablating bothPdgfraandPdgfrbin the murine NCC lineage on earlier craniofacial development and determined the cellular mechanisms by which the observed phenotypes arose. Our results confirm a genetic interaction between the two receptors in this lineage, as phenotypes observed in an allelic series of mutant embryos often worsened with the addition of conditional alleles. The defects observed here were shown to stem from reduced cNCC stream size and aberrant cNCC directional migration, as well as decreased proliferation of the facial mesenchyme upon combined decreases in PDGFRα and PDGFRβ signaling. Importantly, we found that PDGFRα plays a predominant role in cNCC migration whereas PDGFRβ primarily contributes to proliferation of the facial mesenchyme. Our findings provide insight into the distinct mechanisms by which PDGFRα and PDGFRβ signaling regulate cNCC activity and subsequent craniofacial development in the mouse embryo.
Single-nuclei transcriptomics of schizophrenia prefrontal cortex primarily implicates neuronal subtypes
Authors: Reiner Benjamin C. , Crist Richard C. , Stein Lauren M. , Weller Andrew E. , Doyle Glenn A. , Arauco-Shapiro Gabriella , Turecki Gustavo , Ferraro Thomas N. , Hayes Matthew R. , Berrettini Wade H. 
Published: July 2020

AbstractTranscriptomic studies of bulk neural tissue homogenates from persons with schizophrenia and controls have identified differentially expressed genes in multiple brain regions. However, the brain’s heterogeneous nature prevents identification of relevant cell types. This study analyzed single-nuclei transcriptomics of ~275,000 nuclei from frozen human postmortem dorsolateral prefrontal cortex samples from males with schizophrenia (n = 12) and controls (n = 14). 4,766 differential expression events were identified in 2,994 unique genes in 16 of 20 transcriptomically-distinct cell populations. ~96% of differentially expressed genes occurred in five neuronal cell types, and differentially expressed genes were enriched for genes associated with schizophrenia and bipolar GWAS loci. Downstream analyses identified cluster-specific enriched gene ontologies, KEGG pathways, and canonical pathways. Additionally, microRNAs and transcription factors with overrepresented neuronal cell type-specific targets were identified. These results expand our knowledge of disrupted gene expression in specific cell types and permit new insight into the pathophysiology of schizophrenia.
Genomic insights into the host specific adaptation of thePneumocystisgenus and emergence of the human pathogenPneumocystis jirovecii
Authors: Cissé Ousmane H. , Ma Liang , Dekker John P. , Khil Pavel P. , Youn Jung-Ho , Brenchley Jason M. , Blair Robert , Pahar Bapi , Chabé Magali , Van Rompay Koen K.A. , Keesler Rebekah , Sukura Antti , Hirsch Vanessa , Kutty Geetha , Liu Yueqin , Li Peng , Chen Jie , Song Jun , Weissenbacher-Lang Christiane , Xu Jie , Upham Nathan S. , Stajich Jason E. , Cuomo Christina A. , Cushion Melanie T. , Kovacs Joseph A. 
Published: July 2020

AbstractPneumocystis jirovecii, the fungal agent of humanPneumocystispneumonia, is closely related to macaquePneumocystis. Little is known about otherPneumocystisspecies in distantly related mammals, none of which are capable of establishing infection in humans. The molecular basis of host specificity inPneumocystisremains unknown as experiments are limited due to an inability to culture any speciesin vitro. To explorePneumocystisevolutionary adaptations, we have sequenced the genomes of species infecting macaques, rabbits, dogs and rats and compared them to available genomes of species infecting humans, mice and rats. Complete whole genome sequence data enables analysis and robust phylogeny, identification of important genetic features of the host adaptation, and estimation of speciation timing relative to the rise of their mammalian hosts. Our data reveals novel insights into the evolution ofP. jirovecii, the sole member of the genus able to infect humans.
Polygenic Scores Predict the Development of Alcohol and Nicotine Use Problems from Adolescence through Young Adulthood
Authors: Deak Joseph D. , Clark D. Angus , Liu Mengzhen , Durbin C. Emily , Iacono William G. , McGue Matt , Vrieze Scott I. , Hicks Brian M. 
Published: July 2020

AbstractObjectiveMolecular genetic studies of alcohol and nicotine have identified many genome-wide loci. We examined the predictive utility of drinking and smoking polygenic scores (PGS) for alcohol and nicotine use from late childhood to early adulthood, substance-specific versus broader-liability PGS effects, and if PGS performance varied between consumption versus pathological use.MethodsLatent growth curve models with structured residuals were used to assess the predictive utility of drinks per week and regular smoking PGS for measures of alcohol and nicotine consumption and problematic use from age 14 to 34. PGSs were generated from the largest discovery sample for alcohol and nicotine use to date (i.e., GSCAN), and examined for associations with alcohol and nicotine use in the Minnesota Twin Family Study (N=3225).ResultsThe drinking PGS was a significant predictor of age 14 problematic alcohol use and increases in problematic use during young adulthood. The smoking PGS was a significant predictor for all nicotine use outcomes. After adjusting for the effects of both PGSs, the smoking PGS demonstrated incremental predictive utility for most alcohol use outcomes and remained a significant predictor of nicotine use trajectories.ConclusionsHigher PGS for drinking and smoking were associated with more problematic levels of substance use longitudinally. The smoking PGS seems to capture both nicotine-specific and non-specific genetic liability for substance use, and may index genetic risk for broader externalizing behavior. Validation of PGS within longitudinal designs may have important clinical implications should future studies support the clinical utility of PGS for substance use disorders.
Analysis of site and structure specific core fucosylation in liver disease progression using exoglycosidase-assisted data-independent LC-MS/MS
Authors: Sanda Miloslav , Ahn Jaeil , Kozlik Petr , Goldman Radoslav 
Published: July 2020

ABSTRACTCarbohydrates form one of the major groups of biological macromolecules in living organisms. Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation. Fucosylation of proteins regulates such processes and is associated with various diseases including autoimmunity and cancer. Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored. We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides derived from 18 serum proteins in liver disease of different etiologies. Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment. In addition, our results show that disease-associated changes in core fucosylation are peptide-dependent and further differ by branching of the core fucosylated glycans. Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.
Resistance to tembotrione, a 4- Hydroxyphenylpyruvate Dioxygenase-Inhibitor inSorghum bicolor
Authors: Pandian Balaji Aravindhan , Varanasi Aruna , Vennapusa Amaranatha R. , Sathishraj Rajendran , Lin Guifang , Zhao Mingxia , Tunnell Madison , Tesso Tesfaye , Liu Sanzhen , Prasad P.V. Vara , Jugulam Mithila 
Published: July 2020

AbstractPostemergence grass weed control continues to be a big challenge in grain sorghum (Sorghum bicolorL. Moench), primarily due to a lack of herbicide options registered for use in this crop. The development of herbicide-resistant sorghum technology to facilitate broad-spectrum postemergence weed control is an economical and viable solution. The 4-hydroxyphenylpyruvate dioxygenase-inhibitor herbicides (e.g. mesotrione or tembotrione) can control broad-spectrum of weeds including grasses, which, however, is not registered for postemergence application in sorghum due to crop injury. In this study we identified two tembotrione-resistant sorghum genotypes (G-200, G-350) and one highly susceptible genotype (S-1) through screening 317 sorghum lines from the sorghum association panel (SAP). Compared to S-1, G-200 and G-350 exhibited 10- and 7-fold more resistance to tembotrione, respectively. Genetic analyses of the F1and F2progeny generated from a cross between tembotrione-resistant and -susceptible genotypes demonstrated that the resistance is a semi-dominant polygenic trait. Furthermore, cytochrome P450 (CYP)-inhibitor assay using malathion and piperonyl butoxide suggested possible CYP-mediated metabolism of tembotrione in G-200 and G-350. Genotype-by-sequencing based quantitative trait loci (QTL) mapping revealed eight QTLs associated with tembotrione resistance in grain sorghum. Sorghum genotypes G-200 and G-350 confer a high level of metabolic resistance to tembotrione and controlled by a polygenic trait. There is an enormous potential to introgress the tembotrione resistance into breeding lines to develop agronomically desirable sorghum hybrids.One-sentence summaryThis research focuses on characterization, genetic analyses, identification of QTLs-linked to metabolic resistance to tembotrione in Sorghum bicolor, for improved weed control and increased yield