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https://www.readbyqxmd.com/read/29221110/a-seven-gene-signature-predicts-overall-survival-of-patients-with-colorectal-cancer
#1
Huarong Chen, Xiaoqiang Sun, Weiting Ge, Yun Qian, Rui Bai, Shu Zheng
Colorectal cancer (CRC) is a major cause of global cancer mortality. Gene expression profiles can help predict prognosis of patients with CRC. In most of previous studies, disease recurrence was analyzed as the survival endpoint. Thus we aim to build a robust gene signature for prediction of overall survival (OS) in patients with CRC. Fresh frozen CRC tissues from 64 patients were analyzed using Affymetrix HG-U133plus 2.0 gene arrays. By performing univariate survival analysis, 6487 genes were found to be associated with the OS in our cohort...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212035/comprehensive-characterization-of-the-complex-lola-locus-reveals-a-novel-role-in-the-octopaminergic-pathway-via-tyramine-beta-hydroxylase-regulation
#2
Nadja Dinges, Violeta Morin, Nastasja Kreim, Tony D Southall, Jean-Yves Roignant
Longitudinals lacking (lola) is one of the most complex genes in Drosophila melanogaster, encoding up to 20 protein isoforms that include key transcription factors involved in axonal pathfinding and neural reprogramming. Most previous studies have employed loss-of-function alleles that disrupt lola common exons, making it difficult to delineate isoform-specific functions. To overcome this issue, we have generated isoform-specific mutants for all isoforms using CRISPR/Cas9. This enabled us to study specific isoforms with respect to previously characterized roles for Lola and to demonstrate a specific function for one variant in axon guidance via activation of the microtubule-associated factor Futsch...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29211847/changes-in-neuronal-signaling-and-cell-stress-response-pathways-are-associated-with-a-multigenic-response-of-drosophila-melanogaster-to-ddt-selection
#3
Keon Mook Seong, Brad S Coates, Weilin Sun, John M Clark, Barry R Pittendrigh
The adaptation of insect populations to insecticidal control is a continual threat to human health and sustainable agricultural practices, but many complex genomic mechanisms involved in this adaption remain poorly understood. This study applied a systems approach to investigate the interconnections between structural and functional variance in response to dichlorodiphenyltrichloroethane (DDT) within the Drosophila melanogaster strain 91-R. Directional selection in six selective sweeps coincided with constitutive gene expression differences in DDT resistant flies, including the most highly up-regulated transcript, Unc-115b, which plays a central role in axon guidance, and the most highly down-regulated transcript, the angiopoietin-like CG31832, which is involved in directing vascular branching and dendrite outgrowth but likely under trans-regulatory control...
December 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29207951/downstream-mediators-of-ten-m3-signalling-in-the-developing-visual-pathway
#4
Kelly A Glendining, Sam C Liu, Marvin Nguyen, Nuwan Dharmaratne, Rajini Nagarajah, Miguel A Iglesias, Atomu Sawatari, Catherine A Leamey
BACKGROUND: The formation of visuotopically-aligned projections in the brain is required for the generation of functional binocular circuits. The mechanisms which underlie this process are unknown. Ten-m3 is expressed in a broad high-ventral to low-dorsal gradient across the retina and in topographically-corresponding gradients in primary visual centres. Deletion of Ten-m3 causes profound disruption of binocular visual alignment and function. Surprisingly, one of the most apparent neuroanatomical changes-dramatic mismapping of ipsilateral, but not contralateral, retinal axons along the representation of the nasotemporal retinal axis-does not correlate well with Ten-m3's expression pattern, raising questions regarding mechanism...
December 6, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/29202173/dcc-ntn1-complex-mutations-in-patients-with-congenital-hypogonadotropic-hypogonadism-impair-gnrh-neuron-development
#5
Justine Bouilly, Andrea Messina, Georgios Papadakis, Daniele Cassatella, Cheng Xu, James S Acierno, Brooke Tata, Gerasimos Sykiotis, Sara Santini, Yisrael Sidis, Eglantine Elowe-Gruau, Franziska Phan-Hug, Michael Hauschild, Pierre-Marc Bouloux, Richard Quinton, Mariarosaria Lang-Muritano, Lucie Favre, Laura Marino, Paolo Giacobini, Andrew A Dwyer, Nicolas J Niederländer, Nelly Pitteloud
Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disease characterized by absent puberty and infertility due to GnRH deficiency, and is often associated with anosmia (Kallmann syndrome, KS). The genetic etiology of CHH is heterogeneous, and more than 30 genes have been implicated in approximately 50% of patients with CHH. We hypothesized that genes encoding axon-guidance proteins containing fibronectin type-III (FN3) domains (similar to ANOS1, the first gene associated with KS), are mutated in CHH...
November 30, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29199528/gene-networks-associated-with-non-syndromic-intellectual-disability
#6
Soohyun Lee, Stephen Rudd, Jacob Gratten, Peter M Visscher, Johannes B Prins, Paul A Dawson
Non-syndromic intellectual disability (NS-ID) is a genetically heterogeneous disorder, with more than 200 candidate genes to date. Despite the increasing number of novel mutations detected, a relatively low number of recurrently mutated genes have been identified, highlighting the complex genetic architecture of the disorder. A systematic search of PubMed and Medline identified 245 genes harbouring non-synonymous variants, insertions or deletions, which were identified as candidate NS-ID genes from case reports or from linkage or pedigree analyses...
December 4, 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/29196093/sonic-hedgehog-regulates-the-pathfinding-of-descending-serotonergic-axons-in-hindbrain-in-collaboration-with-wnt5a-and-secreted-frizzled-related-protein-1
#7
Jie Xie, Teng Zhao, Yaobo Liu
Previous studies have demonstrated that both Wnt5a and Sonic hedgehog (Shh) are involved in regulating the pathfinding of descending serotonergic (5-HT, 5-hydroxytryptamine) axons in an opposite manner in the brainstem. Shh and Wnt signaling pathways interact to guide post-crossing commissural axons, where Shh acts as a repellent directly and shaping the Wnt gradient indirectly by regulating the gradient expression of the frizzled-related protein 1 (Sfrp1). Whether such a mechanism functions in descending 5-HT axon guidance remains unknown...
November 28, 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/29190463/genipin-treated-chitosan-nanofibers-as-a-novel-scaffold-for-nerve-guidance-channel-design
#8
Yu-Ting Lau, Lam-Fung Kwok, Kin-Wai Tam, Ying-Shing Chan, Daisy Kwok-Yan Shum, Graham Ka-Hon Shea
Schwann cell-seeded nerve guidance channels are designed to assist post-traumatic nerve regeneration in the PNS. Chitosan is a natural polymer well suited for tissue engineering as it is biocompatible, non-immunogenic, and biodegradable. Electrospun chitosan nanofibers utilized in nerve guidance channels have the capacity for guiding axonal growth within the channel lumen yet are limited in their capacity to maintain structural integrity within physiological environments. To address this, we attempted genipin crosslinking of chitosan nanofibers...
November 23, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29189905/complementary-research-models-and-methods-to-study-axonal-regeneration-in-the-vertebrate-retinofugal-system
#9
REVIEW
Ilse Bollaerts, Lien Veys, Emiel Geeraerts, Lien Andries, Lies De Groef, Tom Buyens, Manuel Salinas-Navarro, Lieve Moons, Inge Van Hove
Due to the lack of axonal regeneration, age-related deterioration in the central nervous system (CNS) poses a significant burden on the wellbeing of a growing number of elderly. To overcome this regenerative failure and to improve the patient's life quality, the search for novel regenerative treatment strategies requires valuable (animal) models and techniques. As an extension of the CNS, the retinofugal system, consisting of retinal ganglion cells that send their axons along the optic nerve to the visual brain areas, has importantly contributed to the current knowledge on mechanisms underlying the restricted regenerative capacities and to the development of novel strategies to enhance axonal regeneration...
November 30, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29189775/visualizing-endocytic-recycling-and-trafficking-in-live-neurons-by-subdiffractional-tracking-of-internalized-molecules
#10
Merja Joensuu, Ramon Martínez-Mármol, Pranesh Padmanabhan, Nick R Glass, Nela Durisic, Matthew Pelekanos, Mahdie Mollazade, Giuseppe Balistreri, Rumelo Amor, Justin J Cooper-White, Geoffrey J Goodhill, Frédéric A Meunier
Our understanding of endocytic pathway dynamics is restricted by the diffraction limit of light microscopy. Although super-resolution techniques can overcome this issue, highly crowded cellular environments, such as nerve terminals, can also dramatically limit the tracking of multiple endocytic vesicles such as synaptic vesicles (SVs), which in turn restricts the analytical dissection of their discrete diffusional and transport states. We recently introduced a pulse-chase technique for subdiffractional tracking of internalized molecules (sdTIM) that allows the visualization of fluorescently tagged molecules trapped in individual signaling endosomes and SVs in presynapses or axons with 30- to 50-nm localization precision...
December 2017: Nature Protocols
https://www.readbyqxmd.com/read/29174916/guidance-of-retinal-axons-in-mammals
#11
REVIEW
Eloísa Herrera, Lynda Erskine
In order to navigate through the surrounding environment many mammals, including humans, primarily rely on vision. The eye, composed of the choroid, sclera, retinal pigmented epithelium, cornea, lens, iris and retina, is the structure that receives the light and converts it into electrical impulses. The retina contains six major types of neurons involving in receiving and modifying visual information and passing it onto higher visual processing centres in the brain. Visual information is relayed to the brain via the axons of retinal ganglion cells (RGCs), a projection known as the optic pathway...
November 21, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29174915/midline-axon-guidance-in-the-drosophila-embryonic-central-nervous-system
#12
REVIEW
LaFreda J Howard, Haley E Brown, Benjamin C Wadsworth, Timothy A Evans
Studies in the fruit fly Drosophila melanogaster have provided many fundamental insights into the genetic regulation of neural development, including the identification and characterization of evolutionarily conserved axon guidance pathways and their roles in important guidance decisions. Due to its highly organized and fast-developing embryonic nervous system, relatively small number of neurons, and molecular and genetic tools for identifying, labeling, and manipulating individual neurons or small neuronal subsets, studies of axon guidance in the Drosophila embryonic CNS have allowed researchers to dissect these genetic mechanisms with a high degree of precision...
November 23, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29172953/cortactin-function-in-invadopodia
#13
Pauline Jeannot, Arnaud Besson
Actin remodeling plays an essential role in diverse cellular processes such as cell motility, vesicle trafficking or cytokinesis. The scaffold protein and actin nucleation promoting factor Cortactin is present in virtually all actin-based structures, participating in the formation of branched actin networks. It has been involved in the control of endocytosis, and vesicle trafficking, axon guidance and organization, as well as adhesion, migration and invasion. To migrate and invade through three-dimensional environments, cells have developed specialized actin-based structures called invadosomes, a generic term to designate invadopodia and podosomes...
November 26, 2017: Small GTPases
https://www.readbyqxmd.com/read/29167507/characterization-of-the-early-molecular-changes-in-the-glomeruli-of-cd151-mice-highlights-induction-of-mindin-and-mmp-10
#14
Crystal Naudin, Brian Smith, Danielle R Bond, Matthew D Dun, Rodney J Scott, Leonie K Ashman, Judith Weidenhofer, Séverine Roselli
In humans and FVB/N mice, loss of functional tetraspanin CD151 is associated with glomerular disease characterised by early onset proteinuria and ultrastructural thickening and splitting of the glomerular basement membrane (GBM). To gain insight into the molecular mechanisms associated with disease development, we characterised the glomerular gene expression profile at an early stage of disease progression in FVB/N Cd151 -/- mice compared to Cd151 +/+ controls. This study identified 72 up-regulated and 183 down-regulated genes in FVB/N Cd151 -/- compared to Cd151 +/+ glomeruli (p < 0...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29167405/the-microtubule-associated-protein-tau-mediates-the-organization-of-microtubules-and-their-dynamic-exploration-of-actin-rich-lamellipodia-and-filopodia-of-cortical-growth-cones
#15
Sayantanee Biswas, Katherine Kalil
Proper organization and dynamics of the actin and microtubule (MT) cytoskeleton are essential for growth cone behaviors during axon growth and guidance. The microtubule associated protein tau is known to mediate actin/MT interactions in cell free systems but the role of tau in regulating cytoskeletal dynamics in living neurons is unknown. We used cultures of cortical neurons from postnatal day 0 (P0)-P2 golden Syrian hamsters (Mesocricetus auratus) of either sex to study the role of tau in the organization and dynamics of the axonal growth cone cytoskeleton...
November 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29162653/de-novo-variants-in-ebf3-are-associated-with-hypotonia-developmental-delay-intellectual-disability-and-autism
#16
Akemi J Tanaka, Megan T Cho, Rebecca Willaert, Kyle Retterer, Yuri A Zarate, Katie Bosanko, Vikki Stefans, Kimihiko Oishi, Amy Williamson, Golder N Wilson, Alice Basinger, Tina Barbaro-Dieber, Lucia Ortega, Susanna Sorrentino, Melissa K Gabriel, Ilse J Anderson, Maria J Guillen Sacoto, Rhonda E Schnur, Wendy K Chung
Using whole-exome sequencing, we identified seven unrelated individuals with global developmental delay, hypotonia, dysmorphic facial features, and an increased frequency of short stature, ataxia, and autism with de novo heterozygous frameshift, nonsense, splice, and missense variants in the Early B-cell Transcription Factor Family Member 3 (EBF3) gene. EBF3 is a member of the collier/olfactory-1/early B-cell factor (COE) family of proteins, which are required for central nervous system (CNS) development. COE proteins are highly evolutionarily conserved and regulate neuronal specification, migration, axon guidance, and dendritogenesis during development and are essential for maintaining neuronal identity in adult neurons...
November 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/29155813/post-guidance-signaling-by-extracellular-matrix-associated-slit-slit-n-maintains-fasciculation-and-position-of-axon-tracts-in-the-nerve-cord
#17
Krishna Moorthi Bhat
Axon-guidance by Slit-Roundabout (Robo) signaling at the midline initially guides growth cones to synaptic targets and positions longitudinal axon tracts in discrete bundles on either side of the midline. Following the formation of commissural tracts, Slit is found also in tracts of the commissures and longitudinal connectives, the purpose of which is not clear. The Slit protein is processed into a larger N-terminal peptide and a smaller C-terminal peptide. Here, I show that Slit and Slit-N in tracts interact with Robo to maintain the fasciculation, the inter-tract spacing between tracts and their position relative to the midline...
November 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29155751/dissection-and-immunofluorescent-staining-of-mushroom-body-and-photoreceptor-neurons-in-adult-drosophila-melanogaster-brains
#18
Seth M Kelly, Alexandra Elchert, Michael Kahl
Nervous system development involves a sequential series of events that are coordinated by several signaling pathways and regulatory networks. Many of the proteins involved in these pathways are evolutionarily conserved between mammals and other eukaryotes, such as the fruit fly Drosophila melanogaster, suggesting that similar organizing principles exist during the development of these organisms. Importantly, Drosophila has been used extensively to identify cellular and molecular mechanisms regulating processes that are required in mammals including neurogenesis, differentiation, axonal guidance, and synaptogenesis...
November 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155221/motor-axon-guidance-in-drosophila
#19
REVIEW
Aref Arzan Zarin, Juan-Pablo Labrador
The Drosophila motor system starts to assemble during embryonic development. It is composed of 30 muscles per abdominal hemisegment and 36 motor neurons assembling into nerve branches to exit the CNS, navigate within the muscle field and finally establish specific connections with their target muscles. Several families of guidance molecules that play a role controlling this process as well as transcriptional regulators that program the behavior of specific motoneurons have been identified. In this review we summarize the role of both groups of molecules in the motor system as well as their relationship where known...
November 16, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29155180/cell-membrane-dynamics-induction-using-optogenetic-tools
#20
Yoshibumi Ueda, Moritoshi Sato
Structures arising from actin-based cell membrane movements, including ruffles, lamellipodia, and filopodia, play important roles in a broad spectrum of cellular functions, such as cell motility, axon guidance in neurons, wound healing, and micropinocytosis. Previous studies investigating these cell membrane dynamics often relied on pharmacological inhibition, RNA interference, and constitutive active/dominant negative protein expression systems. However, such studies did not allow the modulation of protein activity at specific regions of cells, tissues, and organs in animals with high spatial and temporal precision...
November 16, 2017: Biochemical and Biophysical Research Communications
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