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Sheila Cardeña-Núñez, Luis Óscar Sánchez-Guardado, Rubén Corral-San-Miguel, Lucía Rodríguez-Gallardo, Faustino Marín, Luis Puelles, Pilar Aroca, Matías Hidalgo-Sánchez
The vertebrate inner ear is a complex three-dimensional sensorial structure with auditory and vestibular functions. The molecular patterning of the developing otic epithelium creates various positional identities, consequently leading to the stereotyped specification of each neurosensory and non-sensory element of the membranous labyrinth. The Iroquois (Iro/Irx) genes, clustered in two groups (A: Irx1, Irx2, and Irx4; and B: Irx3, Irx5, and Irx6), encode for transcriptional factors involved directly in numerous patterning processes of embryonic tissues in many phyla...
October 25, 2016: Brain Structure & Function
Elvin Yildiz, Meltem Tunca Toklu, Ece Turan Vural, Nursal Melda Yenerel, Handan Bardak, Esra Turkseven Kumral, Yavuz Bardak
PURPOSE: To evaluate the accommodative response to different accommodative stimulus and to determine the changes in ocular higher-order aberrations with accommodation in keratoconus patients fitted with mini scleral lenses. MATERIAL AND METHODS: The study included 15 keratoconus patients wearing mini scleral lenses (Misa Scleral Lens-Microlens, Arnhem, the Netherlands) and 15 keratoconus patients wearing rigid gas permeable lenses. Hartmannn Shack aberrometer (IRX-3; Imagine Eyes, Orsay, France) was used for the evaluation of accommodation...
September 7, 2016: Eye & Contact Lens
Kathrin Landgraf, Markus Scholz, Peter Kovacs, Wieland Kiess, Antje Körner
BACKGROUND: Genome-wide association studies have identified variants within the FTO (fat mass and obesity associated) locus as the strongest predictors of obesity amongst all obesity-associated gene loci. Recent evidence suggests that variants in FTO directly affect human adipocyte function through targeting IRX3 and IRX5 and thermogenesis regulation. AIM: We addressed the relevance of this proposed FTO-IRX pathway in adipose tissue (AT) of children. RESULTS: Expression of IRX3 was higher in adipocytes compared to SVF...
2016: PloS One
Corey J Cain, Nathalie Gaborit, Wint Lwin, Emilie Barruet, Samantha Ho, Carine Bonnard, Hanan Hamamy, Mohammad Shboul, Bruno Reversade, Hülya Kayserili, Benoit G Bruneau, Edward C Hsiao
Cranial malformations are a significant cause of perinatal morbidity and mortality. Iroquois homeobox transcription factors (IRX) are expressed early in bone tissue formation and facilitate patterning and mineralization of the skeleton. Mice lacking Irx5 appear grossly normal, suggesting that redundancy within the Iroquois family. However, global loss of both Irx3 and Irx5 in mice leads to significant skeletal malformations and embryonic lethality from cardiac defects. Here, we study the bone-specific functions of Irx3 and Irx5 using Osx-Cre to drive osteoblast lineage-specific deletion of Irx3 in Irx5(-/-) mice...
December 2016: Bone Reports
Pei Wang, Chunbo Zhuang, Da Huang, Keshu Xu
Iroquois homeobox (IRX) gene family, which plays essential roles in embryonic development, has recently been reported to be involved in tumor progression. However, the association of IRX3, a member of the IRX family, with hepatocellular carcinoma (HCC) has not previously been studied. In the present study, we found that IRX3 was upregulated in HCC cell lines (HepG2 and SMMC7721). We investigated the regulatory mechanism of IRX3 in HCC cells. Western blot and luciferase reporter assays identified that IRX3 is a direct target of miR-377...
July 2016: Oncology Reports
Emre Aksoy, Aurélien Vigneron, XiaoLi Bing, Xin Zhao, Michelle O'Neill, Yi-Neng Wu, James D Bangs, Brian L Weiss, Serap Aksoy
Tsetse flies are biological vectors of African trypanosomes, the protozoan parasites responsible for causing human and animal trypanosomiases across sub-Saharan Africa. Currently, no vaccines are available for disease prevention due to antigenic variation of the Variant Surface Glycoproteins (VSG) that coat parasites while they reside within mammalian hosts. As a result, interference with parasite development in the tsetse vector is being explored to reduce disease transmission. A major bottleneck to infection occurs as parasites attempt to colonize tsetse's midgut...
June 21, 2016: Proceedings of the National Academy of Sciences of the United States of America
Cristina M Justice, Kevin Bishop, Blake Carrington, Jim C Mullikin, Kandice Swindle, Beth Marosy, Raman Sood, Nancy H Miller, Alexander F Wilson
Because of genetic heterogeneity present in idiopathic scoliosis, we previously defined clinical subsets (a priori) from a sample of families with idiopathic scoliosis to find genes involved with spinal curvature. Previous genome-wide linkage analysis of seven families with at least two individuals with kyphoscoliosis found linkage (P-value = 0.002) in a 3.5-Mb region on 5p13.3 containing only three known genes, IRX1, IRX2, and IRX4 In this study, the exons of IRX1, IRX2, and IRX4, the conserved noncoding elements in the region, and the exons of a nonprotein coding RNA, LOC285577, were sequenced...
2016: G3: Genes—Genomes—Genetics
Wei Zeng, Edwin R Lampugnani, Kelsey L Picard, Lili Song, Ai-Min Wu, Isabela M Farion, Jia Zhao, Kris Ford, Monika S Doblin, Antony Bacic
Heteroxylans are abundant components of plant cell walls and provide important raw materials for the food, pharmaceutical, and biofuel industries. A number of studies in Arabidopsis (Arabidopsis thaliana) have suggested that the IRREGULAR XYLEM9 (IRX9), IRX10, and IRX14 proteins, as well as their homologs, are involved in xylan synthesis via a Golgi-localized complex termed the xylan synthase complex (XSC). However, both the biochemical and cell biological research lags the genetic and molecular evidence. In this study, we characterized garden asparagus (Asparagus officinalis) stem xylan biosynthesis genes (AoIRX9, AoIRX9L, AoIRX10, AoIRX14A, and AoIRX14B) by heterologous expression in Nicotiana benthamiana We reconstituted and partially purified an active XSC and showed that three proteins, AoIRX9, AoIRX10, and AoIRX14A, are necessary for xylan xylosyltranferase activity in planta...
May 2016: Plant Physiology
Oliver Vöcking, Ioannis Kourtesis, Harald Hausen
BACKGROUND: Development of cerebral eyes is generally based on fine-tuned networks and closely intertwined with the formation of brain and head. Consistently and best studied in insects and vertebrates, many signaling pathways relaying the activity of eye developmental factors to positional information in the head region are characterized. Though known from several organisms, photoreceptors developing outside the head region are much less studied and the course of their development, relation to cerebral eyes and evolutionary origin is in most cases unknown...
2015: EvoDevo
Diane M Da Silva, Andrew W Woodham, Paul H Naylor, James E Egan, Neil L Berinstein, W Martin Kast
Langerhans cells (LCs) are the antigen-presenting cells of the epithelial layer and are responsible for initiating immune responses against skin and mucosa-invading viruses. Human papillomavirus (HPV)-mediated suppression of LC function is a crucial mechanism of HPV immune evasion, which can lead to persistent infection and development of several human cancers, including cervical, anal, and head and neck cancers. The cell-derived cytokine-based biologic, IRX-2, consists of multiple well-defined cytokines and is broadly active on various immune cell subsets...
May 2016: Journal of Interferon & Cytokine Research
Kiwon Ban, Brian Wile, Kyu-Won Cho, Sangsung Kim, Ming-Ke Song, Sang Yoon Kim, Jason Singer, Anum Syed, Shan Ping Yu, Mary Wagner, Gang Bao, Young-Sup Yoon
Isolation of ventricular cardiomyocytes (vCMs) has been challenging due to the lack of specific surface markers. Here we show that vCMs can be purified from differentiating mouse embryonic stem cells (mESCs) using molecular beacons (MBs) targeting specific intracellular mRNAs. We designed MBs (IRX4 MBs) to target mRNA encoding Iroquois homeobox protein 4 (Irx4), a transcription factor specific for vCMs. To purify mESC vCMs, IRX4 MBs were delivered into cardiomyogenically differentiating mESCs, and IRX4 MBs-positive cells were FACS-sorted...
December 8, 2015: Stem Cell Reports
Amjad Askary, Lindsey Mork, Sandeep Paul, Xinjun He, Audrey K Izuhara, Suhasni Gopalakrishnan, Justin K Ichida, Andrew P McMahon, Sonja Dabizljevic, Rodney Dale, Francesca V Mariani, J Gage Crump
An early event in skeletal joint development is the specification of articular chondrocytes at the joint surface. Articular chondrocytes are distinct in producing lower levels of cartilage matrix and not being replaced by bone, yet how they acquire these properties remains poorly understood. Here, we show that two members of the Iroquois transcriptional repressor family, Irx7 and Irx5a, function to block chondrocyte maturation at the developing hyoid joint of zebrafish. These Irx factors suppress the production of cartilage matrix at the joint in part by preventing the activation of a col2a1a enhancer by Sox9a...
November 9, 2015: Developmental Cell
Siwei He, Alison Philbrook, Rebecca McWhirter, Christopher V Gabel, Daniel G Taub, Maximilian H Carter, Isabella M Hanna, Michael M Francis, David M Miller
Neural circuits are actively remodeled during brain development, but the molecular mechanisms that trigger circuit refinement are poorly understood. Here, we describe a transcriptional program in C. elegans that regulates expression of an Ig domain protein, OIG-1, to control the timing of synaptic remodeling. DD GABAergic neurons reverse polarity during larval development by exchanging the locations of pre- and postsynaptic components. In newly born larvae, DDs receive cholinergic inputs in the dorsal nerve cord...
October 5, 2015: Current Biology: CB
Natalia Barrios, Esther González-Pérez, Rosario Hernández, Sonsoles Campuzano
During development, proper differentiation and final organ size rely on the control of territorial specification and cell proliferation. Although many regulators of these processes have been identified, how both are coordinated remains largely unknown. The homeodomain Iroquois/Irx proteins play a key, evolutionarily conserved, role in territorial specification. Here we show that in the imaginal discs, reduced function of Iroquois genes promotes cell proliferation by accelerating the G1 to S transition. Conversely, their increased expression causes cell-cycle arrest, down-regulating the activity of the Cyclin E/Cdk2 complex...
August 2015: PLoS Genetics
Peter J Dyck, Bruce V Taylor, Jenny L Davies, Michelle L Mauermann, William J Litchy, Christopher J Klein, P James B Dyck
Intravenous immunoglobulin [IVIg], plasma exchange [PE], and corticosteroids are efficacious treatment in chronic inflammatory demyelinating polyneuropathy [CIDP]. IVIg is effective in multifocal motor neuropathy [MMN]. NIS, NIS-weakness, sum scores of raw amplitudes of motor fiber (CMAPs) amplitudes, and Dyck/Rankin score provided reliable measures to detect and scale abnormality and reflect change; they are therefore ideal for office management of response-based immunotherapy (R-IRx) of CIDP. Using efficacious R-IRx, a large early and late therapeutic response (≥ one-fourth were in remission or had recovered) was demonstrated in CIDP...
October 2015: Muscle & Nerve
Himanshu Mishra, Shweta Saran
Homeobox genes are compared between genomes in an attempt to understand the evolution of animal development. The ability of the protist, Dictyostelium discoideum, to shift between uni- and multicellularity makes this group ideal for studying the genetic changes that may have occurred during this transition. We present here the first genome-wide classification and comparative genomic analysis of the 14 homeobox genes present in D. discoideum. Based on the structural alignment of the homeodomains, they can be broadly divided into TALE and non-TALE classes...
June 2015: Journal of Biosciences
Sol Pose-Méndez, Eva Candal, Sylvie Mazan, Isabel Rodríguez-Moldes
The cerebellum is present in all extant gnathostomes or jawed vertebrates, of which cartilaginous fishes represent the most ancient radiation. Since the isthmic organizer induces the formation of the cerebellum, comparative genoarchitectonic analysis on the meso-isthmo-cerebellar region of cartilaginous fishes with respect to that of jawless vertebrates could reveal why the isthmic organizer acquires the ability to induce the formation of the cerebellum in gnathostomes. In the present work we analyzed the expression pattern of a variety of genes related to the cerebellar formation and patterning (ScOtx2, ScGbx2, ScFgf8, ScLmx1b, ScIrx1, ScIrx3, ScEn2, ScPax6 and ScLhx9) by in situ hybridization, and the distribution of Pax6 protein in the developing hindbrain of the shark Scyliorhinus canicula...
April 2016: Brain Structure & Function
Kisha Scarlett, Vaishnavi Pattabiraman, Petrina Barnett, Dong Liu, Leonard M Anderson
Angiogenesis is a dynamic process required for embryonic development. However, postnatal vascular growth is characteristic of multiple disease states. Despite insights into the multistep process in which adhesion molecules, extracellular matrix proteins, growth factors, and their receptors work in concert to form new vessels from the preexisting vasculature, there remains a lack of insight of the nuclear transcriptional mechanisms that occur within endothelial cells (ECs) in response to VEGF. Iroquois homeobox gene 3 (Irx3) is a transcription factor of the Iroquois family of homeobox genes...
March 6, 2015: Journal of Biological Chemistry
Trevor C Nordin, Aaron J Done, Tinna Traustadóttir
A single bout of acute exercise increases oxidative stress and stimulates a transient increase in antioxidant enzymes. We asked whether this response would induce protection from a subsequent oxidative challenge, different from that of exercise, and whether the effects were affected by aging. We compared young (20 ± 1 years, n = 8) and older (58 ± 6 years, n = 9) healthy men and women. Resistance to oxidative stress was measured by the F2-isoprostane response to forearm ischemia/reperfusion (I/R) trial...
2014: Age (2005-)
Òscar Martorell, Francisco M Barriga, Anna Merlos-Suárez, Camille Stephan-Otto Attolini, Jordi Casanova, Eduard Batlle, Elena Sancho, Andreu Casali
Activating mutations in Wnt and EGFR/Ras signaling pathways are common in colorectal cancer (CRC). Remarkably, clonal co-activation of these pathways in the adult Drosophila midgut induces "tumor-like" overgrowths. Here, we show that, in these clones and in CRC cell lines, Dpp/TGF-β acts as a tumor suppressor. Moreover, we discover that the Iroquois/IRX-family-protein Mirror downregulates the transcription of core components of the Dpp pathway, reducing its tumor suppressor activity. We also show that this genetic interaction is conserved in human CRC cells, where the Iro/IRX proteins IRX3 and IRX5 diminish the response to TGF-β...
November 2014: EMBO Reports
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