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https://www.readbyqxmd.com/read/28334757/perturbations-in-cell-signaling-elicit-early-cardiac-defects-in-mucopolysaccharidosis-type-ii
#1
Roberto Costa, Andrea Urbani, Marika Salvalaio, Stefania Bellesso, Domenico Cieri, Ilaria Zancan, Mirella Filocamo, Paolo Bonaldo, Ildiko Szabò, Rosella Tomanin, Enrico Moro
Morphogens release and activity can be negatively affected by an impaired glycosaminoglycans (GAGs) turnover and proteoglycans assembly in the extracellular matrix, leading to altered tissue morphogenesis. In this work, we show that loss of Iduronate-2-sulfatase (IDS) activity, affecting GAGs catabolism and responsible for a life-threatening valvulopathy in mucopolysaccharidosis type II (MPSII), triggers early Sonic Hedgehog (Shh) and Wnt/β-catenin signaling defects, leading to aberrant heart development and atrioventricular valve formation in a zebrafish model...
February 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28331138/delayed-expression-of-circulating-tgf-%C3%AE-1-and-bmp-2-levels-in-human-nonunion-long-bone-fracture-healing
#2
Yoshiaki Hara, Mohammad Ghazizadeh, Hajime Shimizu, Hisashi Matsumoto, Nobuyuki Saito, Takanori Yagi, Kazuki Mashiko, Kunihiro Mashiko, Makoto Kawai, Hiroyuki Yokota
BACKGROUND: The healing process of bone fracture requires a well-controlled multistage and sequential order beginning immediately after the injury. However, complications leading to nonunion exist, creating serious problems and costs for patients. Transforming growth factor-beta 1 (TGF-β1) and bone morphogenic protein 2 (BMP-2) are two major growth factors involved in human bone fracture healing by promoting various stages of bone ossification. In this study, we aimed to determine the role of these factors during the fracture healing of human long bones and assess their impacts on nonunion condition...
2017: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
https://www.readbyqxmd.com/read/28322449/tgf-%C3%AE-inhibits-osteogenesis-by-upregulating-the-expression-of-ubiquitin-ligase-smurf1-via-mapk-erk-signaling
#3
Xuewu Sun, Ziang Xie, Yan Ma, Xin Pan, Jiying Wang, Zhijun Chen, Peihua Shi
High incidence of osteoporotic fractures emphasizes the necessity of developing effective measures to promote osteogenesis. In our study, we investigated a possible role of MAPK-ERK signaling in the TGF-β-mediated osteoblastic differentiation. Our results indicated that TGF-β activated the MAPK-ERK pathway and inhibited osteogenesis in mesenchymal pluripotent cell line, C3H10T1/2, and preosteoblastic cell line, MC3T3 cells. And the downregulation of MAPK-ERK signaling using pharmacological inhibitor U0126 and RNA interference rescued osteoblast differentiation suppressed by TGF-β, which was confirmed by Alkaline phosphatase (ALP) staining and alizarrn red staining and the enhanced expression of osteogenesic markers...
March 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28319331/morphogen-interpretation-concentration-time-competence-and-signaling-dynamics
#4
REVIEW
Andreas Sagner, James Briscoe
Tissue patterning during animal development is orchestrated by a handful of inductive signals. Most of these developmental cues act as morphogens, meaning they are locally produced secreted molecules that act at a distance to govern tissue patterning. The iterative use of the same signaling molecules in different developmental contexts demands that signal interpretation occurs in a highly context-dependent manner. Hence the interpretation of signal depends on the specific competence of the receiving cells. Moreover, it has become clear that the differential interpretation of morphogens depends not only on the level of signaling but also the signaling dynamics, particularly the duration of signaling...
March 20, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28318367/combinatorial-control-of-messenger-rnas-by-pumilio-nanos-and-brain-tumor-proteins
#5
René M Arvola, Chase A Weidmann, Traci M Tanaka Hall, Aaron C Goldstrohm
Eukaryotes possess a vast array of RNA-binding proteins (RBPs) that affect mRNAs in diverse ways to control protein expression. Combinatorial regulation of mRNAs by RBPs is emerging as the rule. No example illustrates this as vividly as the partnership of three Drosophila RBPs, Pumilio, Nanos and Brain Tumor, which have overlapping functions in development, stem cell maintenance and differentiation, fertility and neurological processes. Here we synthesize thirty years of research with new insights into their molecular functions and mechanisms of action...
March 20, 2017: RNA Biology
https://www.readbyqxmd.com/read/28298319/analysis-of-axonal-trafficking-via-a-novel-live-imaging-technique-reveals-distinct-hedgehog-transport-kinetics
#6
Joseph R Daniele, Rehan M Baqri, Samuel Kunes
The Drosophila melanogaster (Dmel) eye is an ideal model to study development, intracellular signaling, behavior, and neurodegenerative disease. Interestingly, dynamic data is not commonly employed to investigate eye-specific disease models. Using axonal transport of the morphogen Hedgehog (Hh), which is integral to Dmel eye-brain development and implicated in stem cell maintenance and neoplastic disease, we demonstrate the ability to comprehensively quantify and characterize its trafficking in various neuron types and a neurodegeneration model in live early 3(rd) instar larval Drosophila We find that neuronal Hh, whose kinetics have not been reported previously, favors fast anterograde transport and varies in speed and flux with respect to axonal position...
March 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28298318/a-novel-proteolytic-event-controls-hedgehog-intracellular-sorting-and-distribution-to-receptive-fields
#7
Joseph R Daniele, Tehyen Chu, Sam Kunes
The patterning activity of a morphogen depends on secretion and dispersal mechanisms that shape its distribution to the cells of a receptive field. In the case of the protein Hedgehog (Hh), these mechanisms of secretion and transmission remain unclear. In the developing Drosophila visual system, Hedgehog is partitioned for release at opposite poles of photoreceptor neurons. Release into the retina regulates the progression of eye development; axon transport and release at axon termini trigger the development of postsynaptic neurons in the brain...
March 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28293554/sonic-hedgehog-signaling-in-limb-development
#8
REVIEW
Cheryll Tickle, Matthew Towers
The gene encoding the secreted protein Sonic hedgehog (Shh) is expressed in the polarizing region (or zone of polarizing activity), a small group of mesenchyme cells at the posterior margin of the vertebrate limb bud. Detailed analyses have revealed that Shh has the properties of the long sought after polarizing region morphogen that specifies positional values across the antero-posterior axis (e.g., thumb to little finger axis) of the limb. Shh has also been shown to control the width of the limb bud by stimulating mesenchyme cell proliferation and by regulating the antero-posterior length of the apical ectodermal ridge, the signaling region required for limb bud outgrowth and the laying down of structures along the proximo-distal axis (e...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28292422/buffering-global-variability-of-morphogen-gradients
#9
REVIEW
Ben-Zion Shilo, Naama Barkai
Morphogen gradients determine tissue pattern by triggering differential cell responses to distinct morphogen concentrations. The strict quantitative dependence of the emerging patterns on morphogen distribution raises the challenge of buffering variability in morphogen profile to ensure a reproducible outcome. We describe the underlying principles of two modules for buffering morphogen distribution: buffering morphogen amplitude by storing excess morphogen in a limited spatial region, and buffering morphogen spread by pinning morphogen levels at a distal position through global feedback that adjusts morphogen diffusion or degradation across the tissue...
March 13, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28289197/toll-pathway-is-required-for-wound-induced-expression-of-barrier-repair-genes-in-the-drosophila-epidermis
#10
Amalia Capilla, Dmitry Karachentsev, Rachel A Patterson, Anita Hermann, Michelle T Juarez, William McGinnis
The epidermis serves as a protective barrier in animals. After epidermal injury, barrier repair requires activation of many wound response genes in epidermal cells surrounding wound sites. Two such genes in Drosophila encode the enzymes dopa decarboxylase (Ddc) and tyrosine hydroxylase (ple). In this paper we explore the involvement of the Toll/NF-κB pathway in the localized activation of wound repair genes around epidermal breaks. Robust activation of wound-induced transcription from ple and Ddc requires Toll pathway components ranging from the extracellular ligand Spätzle to the Dif transcription factor...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28279165/root-morphogenic-pathways-in-eucalyptus-grandis-are-modified-by-the-activity-of-protein-arginine-methyltransferases
#11
Krista L Plett, Anita E Raposo, Stephen Bullivant, Ian C Anderson, Sabine C Piller, Jonathan M Plett
BACKGROUND: Methylation of proteins at arginine residues, catalysed by members of the protein arginine methyltransferase (PRMT) family, is crucial for the regulation of gene transcription and for protein function in eukaryotic organisms. Inhibition of the activity of PRMTs in annual model plants has demonstrated wide-ranging involvement of PRMTs in key plant developmental processes, however, PRMTs have not been characterised or studied in long-lived tree species. RESULTS: Taking advantage of the recently available genome for Eucalyptus grandis, we demonstrate that most of the major plant PRMTs are conserved in E...
March 9, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28278222/nuclear-genome-stability-in-long-term-cultivated-callus-lines-of-fagopyrum-tataricum-l-gaertn
#12
Alexander Betekhtin, Magdalena Rojek, Joanna Jaskowiak, Anna Milewska-Hendel, Jolanta Kwasniewska, Yulia Kostyukova, Ewa Kurczynska, Natalya Rumyantseva, Robert Hasterok
Long-term cultivated Fagopyrum tataricum (L.) Gaertn. (Tartary buckwheat) morphogenic and non-morphogenic callus lines are interesting systems for gaining a better understanding of the mechanisms that are responsible for the genetic stability and instability of a plant tissue culture. In this work, we used histological sections and transmission electron microscopy to identify and describe the morphology of the nuclei of all of the analysed callus lines. We demonstrated that the embryogenic callus cells had prominent round nuclei that did not contain heterochromatin clumps in contrast to the non-morphogenic callus lines, in which we found nuclei that had multiple lobes...
2017: PloS One
https://www.readbyqxmd.com/read/28278131/microvesicles-from-the-plasma-of-elderly-subjects-and-from-senescent-endothelial-cells-promote-vascular-calcification
#13
Matilde Alique, María Piedad Ruíz-Torres, Guillermo Bodega, María Victoria Noci, Nuria Troyano, Lourdes Bohórquez, Carlos Luna, Rafael Luque, Andrés Carmona, Julia Carracedo, Rafael Ramírez
Vascular calcification is commonly seen in elderly people, though it can also appear in middle-aged subjects affected by premature vascular aging. The aim of this work is to test the involvement of microvesicles (MVs) produced by senescent endothelial cells (EC) and from plasma of elderly people in vascular calcification. The present work shows that MVs produced by senescent cultured ECs, plus those found in the plasma of elderly subjects, promote calcification in vascular smooth muscle cells. Only MVs from senescent ECs, and from elderly subjects' plasma, induced calcification...
March 8, 2017: Aging
https://www.readbyqxmd.com/read/28276640/prospective-review-of-mesenchymal-stem-cells-differentiation-into-osteoblasts
#14
REVIEW
Priyanka Garg, Matthew M Mazur, Amy C Buck, Meghan E Wandtke, Jiayong Liu, Nabil A Ebraheim
Stem cell research has been a popular topic in the past few decades. This review aims to discuss factors that help regulate, induce, and enhance mesenchymal stem cell (MSC) differentiation into osteoblasts for bone regeneration. The factors analyzed include bone morphogenic protein (BMP), transforming growth factor β (TGF-β), stromal cell-derived factor 1 (SDF-1), insulin-like growth factor type 1 (IGF-1), histone demethylase JMJD3, cyclin dependent kinase 1 (CDK1), fucoidan, Runx2 transcription factor, and TAZ transcriptional coactivator...
March 9, 2017: Orthopaedic Surgery
https://www.readbyqxmd.com/read/28275653/ph20-is-not-expressed-in-murine-cns-and-oligodendrocyte-precursor-cells
#15
Mathieu Marella, Joe Ouyang, Jonathan Zombeck, Chunmei Zhao, Lei Huang, Robert J Connor, Kim B Phan, Michael C Jorge, Marie A Printz, Rudolph D Paladini, Arnold B Gelb, Zhongdong Huang, Gregory I Frost, Barry J Sugarman, Lawrence Steinman, Ge Wei, H Michael Shepard, Daniel C Maneval, Paula J Lapinskas
OBJECTIVE: Expression of Spam1/PH20 and its modulation of high/low molecular weight hyaluronan substrate have been proposed to play an important role in murine oligodendrocyte precursor cell (OPC) maturation in vitro and in normal and demyelinated central nervous system (CNS). We reexamined this using highly purified PH20. METHODS: Steady-state expression of mRNA in OPCs was evaluated by quantitative polymerase chain reaction; the role of PH20 in bovine testicular hyaluronidase (BTH) inhibition of OPC differentiation was explored by comparing BTH to a purified recombinant human PH20 (rHuPH20)...
March 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28273182/protocol-for-efficient-regulation-of-in-vitro-morphogenesis-in-einkorn-triticum-monococcum-l-a-recalcitrant-diploid-wheat-species
#16
Dmitry Miroshnichenko, Inna Chaban, Mariya Chernobrovkina, Sergey Dolgov
Einkorn (Triticum monococcum L.) is A-genome diploid wheat that has a potential to become a useful model for understanding the biology and genomics in Triticeae. Unfortunately, the application of modern technologies such as genetic engineering, RNAi-based gene silencing and genome editing is not available for einkorn as there is no efficient in vitro tissue culture and plant regeneration system. In the present study an efficient and simple protocol for plant regeneration via direct or indirect somatic embryogenesis and organogenesis has been developed...
2017: PloS One
https://www.readbyqxmd.com/read/28268375/directing-the-spatial-patterning-of-motor-neuron-differentiation-in-engineered-microenvironments
#17
Christopher J Demers, Greg Cox, Scott D Collins, Rosemary L Smith
Embryonic development of the spinal cord proceeds through a carefully orchestrated temporal and spatial sequence of chemical cues to provide precise patterning of adult cell types. Recreating this complex microenvironment in a standard cell culture dish is difficult, if not impossible. In this paper, a microfluidic device is used to recapitulate, in vitro, the graded patterning events which occur during early spinal cord development. The microdevice design is developed using COMSOL modeling, with which the spatiotemporal profiles of multiple, diffusible morphogens are simulated...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28260559/umbilical-artery-histomorphometry-a-link-between-the-intrauterine-environment-and-kidney-development
#18
M J DeFreitas, D Mathur, W Seeherunvong, T Cano, C P Katsoufis, S Duara, S Yasin, G Zilleruelo, M M Rodriguez, C L Abitbol
Prematurity is a risk factor for hypertension, vascular stiffness, nephron deficit and adult onset cardiorenal disease. The vascular tree and kidneys share morphogenic drivers that promote maturation in utero before 36 weeks of gestation. Vascular elastin accrual terminates after birth leaving collagen to promote vascular stiffness. Our objective was to determine if the histomorphometry of the umbilical artery, an extension of the aorta, parallels nephron mass across gestational age groups. From a cohort of 54 newborns, 32 umbilical cord specimens were adequate for evaluation...
March 6, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/28253328/reprogramming-of-the-retinoic-acid-pathway-in-decidualizing-human-endometrial-stromal-cells
#19
Rie Ozaki, Keiji Kuroda, Yuko Ikemoto, Asako Ochiai, Akemi Matsumoto, Jun Kumakiri, Mari Kitade, Atsuo Itakura, Joanne Muter, Jan J Brosens, Satoru Takeda
Upon breaching of the endometrial surface epithelium, the implanting embryo embeds in the decidualizing stroma. Retinoic acid (RA), a metabolite of vitamin A, is an important morphogen during embryonic and fetal development, although the role of the RA pathway in the surrounding decidual cells is not understood. Here we show that decidual transformation of human endometrial stromal cells (HESCs) results in profound reprogramming of the RA signaling and metabolism pathways. Differentiating HESCs downregulate the intracellular carrier proteins CRABP2 and FABP5, responsible for transfer and binding of RA to the nuclear receptors RAR and PPARβ/δ, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28246332/metabolic-origins-of-spatial-organization-in-the-tumor-microenvironment
#20
Carlos Carmona-Fontaine, Maxime Deforet, Leila Akkari, Craig B Thompson, Johanna A Joyce, Joao B Xavier
The genetic and phenotypic diversity of cells within tumors is a major obstacle for cancer treatment. Because of the stochastic nature of genetic alterations, this intratumoral heterogeneity is often viewed as chaotic. Here we show that the altered metabolism of cancer cells creates predictable gradients of extracellular metabolites that orchestrate the phenotypic diversity of cells in the tumor microenvironment. Combining experiments and mathematical modeling, we show that metabolites consumed and secreted within the tumor microenvironment induce tumor-associated macrophages (TAMs) to differentiate into distinct subpopulations according to local levels of ischemia and their position relative to the vasculature...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
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