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Yoichi Shinkai, Masahiro Kuramochi, Motomichi Doi
Newborn neurons mature by distinct and sequential steps through the timely induction of specific gene expression programs in concert with epigenetic changes. However, it has been difficult to investigate the relationship between gene expression and epigenetic changes at a single-cell resolution during neuronal maturation. In this study, we investigated the maturation of hermaphrodite-specific neurons (HSNs) in C. elegans, which provided the link between chromatin dynamics, gene expression, and the degree of neuronal maturation at a single-cell resolution...
May 21, 2018: Scientific Reports
James H Catterson, Mobina Khericha, Miranda C Dyson, Alec J Vincent, Rebecca Callard, Steven M Haveron, Arjunan Rajasingam, Mumtaz Ahmad, Linda Partridge
Intermittent fasting (IF) can improve function and health during aging in laboratory model organisms, but the mechanisms at work await elucidation. We subjected fruit flies (Drosophila melanogaster) to varying degrees of IF and found that just one month of a 2-day fed:5-day fasted IF regime at the beginning of adulthood was sufficient to extend lifespan. This long-lasting, beneficial effect of early IF was not due to reduced fecundity. Starvation resistance and resistance to oxidative and xenobiotic stress were increased after IF...
May 8, 2018: Current Biology: CB
Denis Odokonyero, Andrew W McMillan, Udupi A Ramagopal, Rafael Toro, Dat P Truong, Mingzhao Zhu, Mariana S Lopez, Belema Somiari, Meghann Herman, Asma Aziz, Jeffrey B Bonanno, Kenneth G Hull, Stephen K Burley, Daniel Romo, Steven C Almo, Margaret E Glasner
Studying the evolution of catalytically promiscuous enzymes like those from the N-succinylamino acid racemase/ o-succinylbenzoate synthase (NSAR/OSBS) subfamily can reveal mechanisms by which new functions evolve. Some enzymes in this subfamily only have OSBS activity, while others catalyze OSBS and NSAR reactions. We characterized several NSAR/OSBS subfamily enzymes as a step toward determining the structural basis for evolving NSAR activity. Three enzymes were promiscuous, like most other characterized NSAR/OSBS subfamily enzymes...
May 16, 2018: Biochemistry
M Knopp, D I Andersson
Antibiotic-resistant bacteria represent a major threat to our ability to treat bacterial infections. Two factors that determine the evolutionary success of antibiotic resistance mutations are their impact on resistance level and the fitness cost. Recent studies suggest that resistance mutations commonly show epistatic interactions, which would complicate predictions of their stability in bacterial populations. We analyzed 13 different chromosomal resistance mutations and 10 host strains of Salmonella enterica and Escherichia coli to address two main questions...
May 15, 2018: MBio
Kunlin Zhang, Li Wang, Chengqi Cao, Gen Li, Ruojiao Fang, Ping Liu, Shu Luo, Xiangyang Zhang, Israel Liberzon
Objective: Post-traumatic stress disorder (PTSD) is a trauma- and stress-related psychiatric syndrome that occurs after exposure to extraordinary stressors. The neurotransmitter dopamine (DA) plays important roles in neurobiological processes like reward and stress, and a link between PTSD and the dopaminergic system has been reported. Thus, the investigation of an association between PTSD and gene-gene interaction (epistasis) within dopaminergic genes could uncover the genetic basis of dopamine-related PTSD symptomatology and contribute to precision medicine...
2018: Frontiers in Psychiatry
Sushil Kumar, Charles Tom Hash, Thirunavukkarasu Nepolean, Mahesh D Mahendrakar, Chellapilla Tara Satyavathi, Govind Singh, Abhishek Rathore, Rattan S Yadav, Rajeev Gupta, Rakesh K Srivastava
Pearl millet is a climate-resilient nutritious crop requiring low inputs and is capable of giving economic returns in marginal agro-ecologies. In this study, we report large-effect iron (Fe) and zinc (Zn) content quantitative trait loci ( QTLs) using diversity array technology (DArT) and simple sequence repeats (SSRs) markers to generate a genetic linkage map using 317 recombinant inbred line (RIL) population derived from the (ICMS 8511-S1-17-2-1-1-B-P03 × AIMP 92901-S1-183-2-2-B-08) cross. The base map [seven linkage groups (LGs)] of 196 loci was 964...
May 11, 2018: Genes
James S Santangelo, Marc T J Johnson, Rob W Ness
Urban environments offer the opportunity to study the role of adaptive and non-adaptive evolutionary processes on an unprecedented scale. While the presence of parallel clines in heritable phenotypic traits is often considered strong evidence for the role of natural selection, non-adaptive evolutionary processes can also generate clines, and this may be more likely when traits have a non-additive genetic basis due to epistasis. In this paper, we use spatially explicit simulations modelled according to the cyanogenesis (hydrogen cyanide, HCN) polymorphism in white clover ( Trifolium repens ) to examine the formation of phenotypic clines along urbanization gradients under varying levels of drift, gene flow and selection...
May 16, 2018: Proceedings. Biological Sciences
Huong Thi Thu Phung, Hoa Luong Hieu Nguyen, Sang Thanh Vo, Dung Hoang Nguyen, Minh Van Le
Mus81 is a well conserved DNA structure-specific endonuclease which belongs to the XPF/Rad1 family of proteins that are involved in DNA nucleotide excision repair. Mus81 forms a heterodimer with a non-catalytic subunit, Mms4 in Saccharomyces cerevisiae (Eme1/EME1 in Schizosaccharomyces pombe and mammals). Recent evidence shows that Mus81 functions redundantly with Sgs1, a member of the ubiquitous RecQ family of DNA helicases, to process toxic recombinant intermediates. In budding yeast, homologous recombination is regulated by the Rad52 epistasis group of proteins, including Rad52, which stimulates the main steps of DNA sequence-homology searching...
May 8, 2018: Yeast
Caitlin Lienkaemper, Lisa Lamberti, James Drain, Niko Beerenwinkel, Alex Gavryushkin
We present an efficient computational approach for detecting genetic interactions from fitness comparison data together with a geometric interpretation using polyhedral cones associated to partial orderings. Genetic interactions are defined by linear forms with integer coefficients in the fitness variables assigned to genotypes. These forms generalize several popular approaches to study interactions, including Fourier-Walsh coefficients, interaction coordinates, and circuits. We assume that fitness measurements come with high uncertainty or are even unavailable, as is the case for many empirical studies, and derive interactions only from comparisons of genotypes with respect to their fitness, i...
May 7, 2018: Journal of Mathematical Biology
Inhye Lee, Kuglae Kim, Sumin Lee, Seungjun Lee, Eunjin Hwang, Kihye Shin, Dayoung Kim, Jungki Choi, Hyunmo Choi, Jeong Seok Cha, Hoyoung Kim, Rin-A Lee, Suyeong Jeong, Jeongsik Kim, Yumi Kim, Hong Gil Nam, Soon-Ki Park, Hyun-Soo Cho, Moon-Soo Soh
A smoke-derived compound, karrikin (KAR) and endogenous, as yet unidentified, KAI2 ligand (KL) are newly emerging chemical cues for higher plants, impacting on multiple aspects of growth and development. Our forward genetic screening toward light-signaling mutants identified a mutant in Arabidopsis thaliana, designated as ply2 (pleiotropic long hypocotyl2), that had pleiotropic light-response defects. Positional cloning identified the molecular lesion of ply2 as a missense mutation of KARRIKIN INSENSITIVE2 (KAI2)/HYPOSENSITIVE TO LIGHT, which causes single amino acid substitution Ala219Val...
May 2, 2018: Journal of Experimental Botany
Yi-Wei Chen, Wen-Chien Ko, Chang-Shi Chen, Po-Lin Chen
Innate immunity is the primary defense mechanism against infection in metazoans. However, aberrant upregulation of innate immune-signaling pathways can also be detrimental to the host. The p38 MAPK/PMK-1 innate immune-signaling pathway has been demonstrated to play essential roles in cellular defenses against numerous infections in metazoans, including Caenorhabditis elegans . However, the negative regulators that maintain the homeostasis of this important innate immune pathway remain largely understudied. By screening a focused RNAi library against the kinome of C...
2018: Frontiers in Immunology
Shan-Shan Dong, Shi Yao, Yi-Xiao Chen, Yan Guo, Yu-Jie Zhang, Hui-Min Niu, Ruo-Han Hao, Hui Shen, Qing Tian, Hong-Wen Deng, Tie-Lin Yang
BACKGROUND: Genome-wide association studies have identified many susceptibility loci for obesity. However, missing heritability problem is still challenging and ignorance of genetic interactions is believed to be an important cause. Current methods for detecting interactions usually do not consider regulatory elements in non-coding regions. Interaction analyses within chromatin regulatory circuitry may identify new susceptibility loci. METHODS: We developed a pipeline named interaction analyses within chromatin regulatory circuitry (IACRC), to identify genetic interactions impacting body mass index (BMI)...
May 1, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Elizabeth R Piette, Jason H Moore
Background: Machine learning methods and conventions are increasingly employed for the analysis of large, complex biomedical data sets, including genome-wide association studies (GWAS). Reproducibility of machine learning analyses of GWAS can be hampered by biological and statistical factors, particularly so for the investigation of non-additive genetic interactions. Application of traditional cross validation to a GWAS data set may result in poor consistency between the training and testing data set splits due to an imbalance of the interaction genotypes relative to the data as a whole...
2018: BioData Mining
Shefali S Verma, Anastasia Lucas, Xinyuan Zhang, Yogasudha Veturi, Scott Dudek, Binglan Li, Ruowang Li, Ryan Urbanowicz, Jason H Moore, Dokyoon Kim, Marylyn D Ritchie
Background: Machine learning methods have gained popularity and practicality in identifying linear and non-linear effects of variants associated with complex disease/traits. Detection of epistatic interactions still remains a challenge due to the large number of features and relatively small sample size as input, thus leading to the so-called "short fat data" problem. The efficiency of machine learning methods can be increased by limiting the number of input features. Thus, it is very important to perform variable selection before searching for epistasis...
2018: BioData Mining
Fang Fang, Benjamin Angulo, Ninuo Xia, Meena Sukhwani, Zhengyuan Wang, Charles C Carey, Aurélien Mazurie, Jun Cui, Royce Wilkinson, Blake Wiedenheft, Naoko Irie, M Azim Surani, Kyle E Orwig, Renee A Reijo Pera
Dysregulation of genetic pathways during human germ cell development leads to infertility. Here, we analysed bona fide human primordial germ cells (hPGCs) to probe the developmental genetics of human germ cell specification and differentiation. We examined the distribution of OCT4 occupancy in hPGCs relative to human embryonic stem cells (hESCs). We demonstrated that development, from pluripotent stem cells to germ cells, is driven by switching partners with OCT4 from SOX2 to PAX5 and PRDM1. Gain- and loss-of-function studies revealed that PAX5 encodes a critical regulator of hPGC development...
April 30, 2018: Nature Cell Biology
Sandipan Dutta, Jean-Pierre Eckmann, Albert Libchaber, Tsvi Tlusty
The function of proteins arises from cooperative interactions and rearrangements of their amino acids, which exhibit large-scale dynamical modes. Long-range correlations have also been revealed in protein sequences, and this has motivated the search for physical links between the observed genetic and dynamic cooperativity. We outline here a simplified theory of protein, which relates sequence correlations to physical interactions and to the emergence of mechanical function. Our protein is modeled as a strongly coupled amino acid network with interactions and motions that are captured by the mechanical propagator, the Green function...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
José Suazo, José Luis Santos, Alicia Colombo, Rosa Pardo
OBJECTIVE: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a birth defect for which several genes susceptibility genes been proposed. Consequently, it has been suggested that many of these genes belong to common inter-related pathways during craniofacial development gene-gene interaction. We evaluated the presence of gene-gene interaction for single nucleotide polymorphisms within interferon regulatory factor 6 (IRF6), muscle segment homeobox 1 (MSX1), bone morphogenetic protein 4 (BMP4) and transforming growth factor 3 (TGFB3) genes in NSCL/P risk in Chilean case-parent trios...
April 18, 2018: Archives of Oral Biology
Bowen Yang, Shunju Xu, Liang Xu, Hui You, Xunchao Xiang
The Wx gene encodes a granule-bound starch synthase (GBSS) and plays a key role in determining rice eating and cooking qualities (ECQs). SSIII-2 (SSIIIa), a member of the soluble starch synthases, is responsible for the synthesis of long chains of amylopectin. To investigate the effects of Wx and its interaction with SSIII-2 on grain ECQs, a population from a hybrid combination was established as a research material. The genotypes of SSIII-2 and the single nucleotide polymorphisms (SNPs) on intron1, exon6, and exon10 of Wx , and the physicochemical indicators and rapid visco analyzer (RVA) profile characteristics were analyzed...
2018: Frontiers in Plant Science
Miriam Kaltenbach, Jason R Burke, Mirco Dindo, Anna Pabis, Fabian S Munsberg, Avigayel Rabin, Shina C L Kamerlin, Joseph P Noel, Dan S Tawfik
The emergence of catalysis in a noncatalytic protein scaffold is a rare, unexplored event. Chalcone isomerase (CHI), a key enzyme in plant flavonoid biosynthesis, is presumed to have evolved from a nonenzymatic ancestor related to the widely distributed fatty-acid binding proteins (FAPs) and a plant protein family with no isomerase activity (CHILs). Ancestral inference supported the evolution of CHI from a protein lacking isomerase activity. Further, we identified four alternative founder mutations, i.e., mutations that individually instated activity, including a mutation that is not phylogenetically traceable...
April 23, 2018: Nature Chemical Biology
Annika Thomer, Maren Gottschalk, Anna Christmann, Fanny Naccache, Klaus Jung, Marion Hewicker-Trautwein, Ottmar Distl, Julia Metzger
Curly coat represents an extraordinary type of coat in horses, particularly seen in American Bashkir Curly Horses and Missouri Foxtrotters. In some horses with curly coat, a hypotrichosis of variable extent was observed, making the phenotype appear more complex. In our study, we aimed at investigating the genetic background of curly coat with and without hypotrichosis using high density bead chip genotype and next generation sequencing data. Genome-wide association analysis detected significant signals (p = 1...
April 23, 2018: Scientific Reports
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