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Tsung-Ting Tsai, Chia-Ling Chen, Yee-Shin Lin, Chih-Peng Chang, Cheng-Chieh Tsai, Yi-Lin Cheng, Chao-Ching Huang, Chien-Jung Ho, Yi-Chao Lee, Liang-Tzung Lin, Ming-Kai Jhan, Chiou-Feng Lin
Patients with dengue virus (DENV) infection may also present acute viral encephalitis through an unknown mechanism. Here, we report that encephalitic DENV-infected mice exhibited progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality 7 days post-infection. These symptoms were accompanied by CNS inflammation, neurotoxicity, and blood-brain barrier destruction. Microglial cells surrounding the blood vessels and injured hippocampus regions were activated by DENV infection. Pharmacologically depleting microglia unexpectedly increased viral replication, neuropathy, and mortality in DENV-infected mice...
2016: Scientific Reports
Kade P Pettie, Jacqueline M Dresch, Robert A Drewell
In the development of the Drosophila embryo, gene expression is directed by the sequence-specific interactions of a large network of protein transcription factors (TFs) and DNA cis-regulatory binding sites. Once the identity of the typically 8-10bp binding sites for any given TF has been determined by one of several experimental procedures, the sequences can be represented in a position weight matrix (PWM) and used to predict the location of additional TF binding sites elsewhere in the genome. Often, alignments of large (>200bp) genomic fragments that have been experimentally determined to bind the TF of interest in Chromatin Immunoprecipitation (ChIP) studies are trimmed under the assumption that the majority of the binding sites are located near the center of all the aligned fragments...
August 2016: Mechanisms of Development
Junbo Liu, Yanyu Xiao, Tongli Zhang, Jun Ma
In a recent study, we investigated the regulation of hunchback (hb) transcription dynamics in Drosophila embryos. Our results suggest that shutdown of hb transcription at early nuclear cycle (nc) 14 is an event associated with the global changes taking place during the mid-blastula transition (MBT). Here we have developed a simple model of hb transcription dynamics during this transition time. With kinetic parameters estimated from our published experimental data, the model describes the dynamical processes of hb gene transcription and hb mRNA accumulation...
July 2, 2016: Fly
Susanta K Behura, Joseph Sarro, Ping Li, Keshava Mysore, David W Severson, Scott J Emrich, Molly Duman-Scheel
BACKGROUND: Despite substantial progress in mosquito genomic and genetic research, few cis-regulatory elements (CREs), DNA sequences that control gene expression, have been identified in mosquitoes or other non-model insects. Formaldehyde-assisted isolation of regulatory elements paired with DNA sequencing, FAIRE-seq, is emerging as a powerful new high-throughput tool for global CRE discovery. FAIRE results in the preferential recovery of open chromatin DNA fragments that are not bound by nucleosomes, an evolutionarily conserved indicator of regulatory activity, which are then sequenced...
2016: BMC Genomics
Alexander V Spirov, Ekaterina M Myasnikova, David M Holloway
Gene network simulations are increasingly used to quantify mutual gene regulation in biological tissues. These are generally based on linear interactions between single-entity regulatory and target genes. Biological genes, by contrast, commonly have multiple, partially independent, cis-regulatory modules (CRMs) for regulator binding, and can produce variant transcription and translation products. We present a modeling framework to address some of the gene regulatory dynamics implied by this biological complexity...
April 2016: Journal of Bioinformatics and Computational Biology
Antoine Desseaux, Michel Pionnier, Bernard Guillemin, Alain Charles Masquelet, Didier Maynart, Frédéric Dubrana
François Humbert (1776-1850) created in 1817 the first French orthopaedic institution, at a great turning point in orthopedics. Interested in "lame people" and "hunchbacks", he treated congenital hip dislocation and scoliosis, for about 30 years. Humbert's medical practice illustrated very well the deep transformation which occured in orthopedics at the beginning of the 19th century. As testimonies of Humbert's work, there are the books he published, his Memoirs, some buildings of his institution which have been reconverted into houses, but above all thirty-eight models of his "machines"...
July 2015: Histoire des Sciences Médicales
Hajime Nakao
Insect segment number within species appears to be fixed irrespective of germ types: long vs. short/intermediate. The present study showed induction of supernumerary segment formation by the knockdown of Bombyx hunchback (Bm-hb), presumably by terminal segment addition, a short/intermediate-like-segmentation mode that is not observed in normal Bombyx embryogenesis. This suggests that Bm-hb suppresses segmentation. The results obtained also suggest that the gap gene Bm-Kr (Bombyx Krüppel) provides a permissive environment for the progression of segmentation by suppressing the expression Bm-hb, which terminates segmentation...
May 15, 2016: Developmental Biology
Bruce R Southey, Ping Zhu, Morgan K Carr-Markell, Zhengzheng S Liang, Amro Zayed, Ruiqiang Li, Gene E Robinson, Sandra L Rodriguez-Zas
Among forager honey bees, scouts seek new resources and return to the colony, enlisting recruits to collect these resources. Differentially expressed genes between these behaviors and genetic variability in scouting phenotypes have been reported. Whole-genome sequencing of 44 Apis mellifera scouts and recruits was undertaken to detect variants and further understand the genetic architecture underlying the behavioral differences between scouts and recruits. The median coverage depth in recruits and scouts was 10...
2016: PloS One
Jean-Michel Carter, Melanie Gibbs, Casper J Breuker
The maternal effect genes responsible for patterning the embryo along the antero-posterior (AP) axis are broadly conserved in insects. The precise function of these maternal effect genes is the result of the localisation of their mRNA in the oocyte. The main developmental mechanisms involved have been elucidated in Drosophila melanogaster, but recent studies have shown that other insect orders often diverge in RNA localisation patterns. A recent study has shown that in the butterfly Pararge aegeria the distinction between blastodermal embryonic (i...
2015: PloS One
B Kladny
Hippocrates was the first to intensively describe and document the principles for the treatment of injuries and diseases of the spine. His principles for abrupt treatment of the "hunchback" were followed by physicians even up to the end of the nineteenth century. The non-operative treatment of scoliosis was improved in the beginning of the sixteenth century by the introduction of mechanical devices that started the development of corsets which are still in use in modern scoliosis treatment. Stretching beds were only in temporary use...
December 2015: Der Unfallchirurg
David Cheung, Jun Ma
A well-appreciated general feature of development is the ability to achieve a normal outcome despite the inevitable variability at molecular, genetic, or environmental levels. But it is not well understood how changes in a global factor such as temperature bring about specific challenges to a developmental system in molecular terms. Here we address this question using early Drosophila embryos where the maternal gradient Bicoid (Bcd) instructs anterior-patterning (AP) patterning. We show that temperature can impact the amplitude of the Bcd gradient in the embryo...
August 19, 2015: Scientific Reports
Jacques P Bothma, Hernan G Garcia, Samuel Ng, Michael W Perry, Thomas Gregor, Michael Levine
Metazoan genes are embedded in a rich milieu of regulatory information that often includes multiple enhancers possessing overlapping activities. In this study, we employ quantitative live imaging methods to assess the function of pairs of primary and shadow enhancers in the regulation of key patterning genes-knirps, hunchback, and snail-in developing Drosophila embryos. The knirps enhancers exhibit additive, sometimes even super-additive activities, consistent with classical gene fusion studies. In contrast, the hunchback enhancers function sub-additively in anterior regions containing saturating levels of the Bicoid activator, but function additively in regions where there are diminishing levels of the Bicoid gradient...
August 12, 2015: ELife
Heng Xu, Leonardo A Sepúlveda, Lauren Figard, Anna Marie Sokac, Ido Golding
We combine immunofluorescence and single-molecule fluorescence in situ hybridization (smFISH), followed by automated image analysis, to quantify the concentration of nuclear transcription factors, number of transcription factors bound, and number of nascent mRNAs synthesized at individual gene loci. A theoretical model is used to decipher how transcription factor binding modulates the stochastic kinetics of mRNA production. We demonstrate this approach by examining the regulation of hunchback in the early Drosophila embryo...
August 2015: Nature Methods
Franziska Anni Franke, Georg Mayer
Zinc finger transcription factors encoded by hunchback homologs play different roles in arthropods, including maternally mediated control, segmentation, and mesoderm and neural development. Knockdown experiments in spider and insect embryos have also revealed homeotic effects and gap phenotypes, the latter indicating a function of hunchback as a "gap gene". Although the expression pattern of hunchback has been analysed in representatives of all four major arthropod groups (chelicerates, myriapods, crustaceans and insects), nothing is known about its expression in one of the closest arthropod relatives, the Onychophora (velvet worms)...
July 2015: Development Genes and Evolution
Chitvan Khajuria, Ana M Vélez, Murugesan Rangasamy, Haichuan Wang, Elane Fishilevich, Meghan L F Frey, Newton Portilho Carneiro, Premchand Gandra, Kenneth E Narva, Blair D Siegfried
RNA interference (RNAi) is being developed as a potential tool for insect pest management and one of the most likely target pest species for transgenic plants that express double stranded RNA (dsRNA) is the western corn rootworm. Thus far, most genes proposed as targets for RNAi in rootworm cause lethality in the larval stage. In this study, we describe RNAi-mediated knockdown of two developmental genes, hunchback (hb) and brahma (brm), in the western corn rootworm delivered via dsRNA fed to adult females. dsRNA feeding caused a significant decrease in hb and brm transcripts in the adult females...
August 2015: Insect Biochemistry and Molecular Biology
Guo-Dong Zhao, Yi-Ling Zhang, Yun-Lei Liu, Bing Li, Yu-Hua Chen, Ya-Xiang Xu, Qing-You Xia, Wei-De Shen, Zheng-Guo Wei
In insects, cytochrome P450 monooxygenases (P450s) are involved in the metabolism of endogenous compounds such as steroid hormones and lipids. In this study, we measured the 20-hydroxyecdysone (20E)-induced transcriptional level of the CYP6ab4 gene using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) with a dual spike-in strategy. We then probed possible physiological functions using RNAi experiments in the silkworm Bombyx mori. The activity of the CYP6ab4 promoter in various silkworm tissues was measured by firefly luciferase activity and normalized by Renilla luciferase activity...
October 2015: Molecular Genetics and Genomics: MGG
Yoshito Kadota, Yuka Aki, Yuriko Toriuchi, Yuto Mizuno, Takashige Kawakami, Masao Sato, Shinya Suzuki
Metallothionein (MT) family proteins are small molecular weight and cysteine-rich proteins that regulate zinc homeostasis and have potential protective effects against oxidative stress and toxic metals. To investigate whether MTs play a role in longevity determination in mammals, we measured the lifespans of wild-type (WT) and MT-1 and -2 gene knockout (MTKO) mice in a 129/Sv genetic background. MTKO mice of both sexes had shorter lifespans than WT mice. In particular, male MTKO mice living beyond the mean lifespan exhibited signs of weight loss, hunchbacked spines, lackluster fur and an absence of vigor...
June 2015: Experimental Gerontology
David M Holloway, Alexander V Spirov
In early development, genes are expressed in spatial patterns which later define cellular identities and tissue locations. The mechanisms of such pattern formation have been studied extensively in early Drosophila (fruit fly) embryos. The gap gene hunchback (hb) is one of the earliest genes to be expressed in anterior-posterior (AP) body segmentation. As a transcriptional regulator for a number of downstream genes, the spatial precision of hb expression can have significant effects in the development of the body plan...
2015: PloS One
Karl R Wotton, Eva Jiménez-Guri, Johannes Jaeger
Axis specification and segment determination in dipteran insects are an excellent model system for comparative analyses of gene network evolution. Antero-posterior polarity of the embryo is established through systems of maternal morphogen gradients. In Drosophila melanogaster, the anterior system acts through opposing gradients of Bicoid (Bcd) and Caudal (Cad), while the posterior system involves Nanos (Nos) and Hunchback (Hb) protein. These systems act redundantly. Both Bcd and Hb need to be eliminated to cause a complete loss of polarity resulting in mirror-duplicated abdomens, so-called bicaudal phenotypes...
March 2015: PLoS Genetics
Pierre Mattar, Johan Ericson, Seth Blackshaw, Michel Cayouette
Neural progenitors alter their output over time to generate different types of neurons and glia in specific chronological sequences, but this process remains poorly understood in vertebrates. Here we show that Casz1, the vertebrate ortholog of the Drosophila temporal identity factor castor, controls the production of mid-/late-born neurons in the murine retina. Casz1 is expressed from mid/late stages in retinal progenitor cells (RPCs), and conditional deletion of Casz1 increases production of early-born retinal neurons at the expense of later-born fates, whereas precocious misexpression of Casz1 has the opposite effect...
February 4, 2015: Neuron
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