journal
MENU ▼
Read by QxMD icon Read
search

Disease Models & Mechanisms

journal
https://www.readbyqxmd.com/read/28213588/a-differential-autophagy-dependent-response-to-dna-double-strand-brakes-in-bone-marrow-mesenchymal-stem-cells-from-sporadic-als-patients
#1
Shane Wald-Altman, Edward Pichinuk, Or Kakhlon, Miguel Weil
Amyotrophic Lateral Sclerosis (ALS) is an incurable motor neurodegenerative disease caused by a diversity of genetic and environmental factors leading to neuromuscular degeneration and pathophysiological implications in non-neural systems. Our previous work showed abnormal transcriptional expression levels of biomarker genes in non-neuronal cell samples from ALS patients. The same genes proved to be differentially expressed in brain, spinal cord and muscle of the SOD1(G93A) ALS mouse model. These observations support the pathophysiological relevance of the ALS biomarkers discovered in human mesenchymal stem cells (hMSC) isolated from bone marrow samples of ALS patients (ALS-hMSC)...
February 16, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28188264/immortalized-human-myotonic-dystrophy-muscle-cell-lines-to-assess-therapeutic-compounds
#2
Arandel Ludovic, Polay-Espinosa Micaela, Matloka Magdalena, Bazinet Audrey, De Dea Diniz Damily, Naouar Naïra, Rau Frédérique, Jollet Arnaud, Edom-Vovard Frédérique, Mamchaoui Kamel, Tarnopolsky Mark, Puymirat Jack, Battail Christophe, Boland Anne, Deleuze Jean-Francois, Mouly Vincent, Klein F Arnaud, Furling Denis
Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA-aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared to control and DM2 cells...
February 10, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28188263/overexpression-of-mitochondrial-oxodicarboxylate-carrier-odc1-preserves-oxidative-phosphorylation-in-a-yeast-model-of-the-barth-syndrome
#3
Maxence de Taffin de Tilques, Déborah Tribouillard-Tanvier, Emmanuel Tétaud, Eric Testet, Jean-Paul di Rago, Jean-Paul Lasserre
Cardiolipin (CL) is a diglycerol phospholipid mostly found in mitochondria where it optimizes numerous processes including oxidative phosphorylation (OXPHOS). To function properly CL needs to be unsaturated, which requires the acyltransferase tafazzin. Loss-of-function mutations in this protein are responsible for the Barth syndrome (BTHS), presumably because of a diminished OXPHOS capacity. Here we show that overexpressing Odc1p, a conserved oxodicarboxylic acid carrier located in the mitochondrial inner membrane, fully restores oxidative phosphorylation in a yeast model (taz1Δ) of the Barth syndrome...
February 10, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28188262/mapk-signaling-pathways-and-hdac3-activity-are-disrupted-during-emerin-null-myogenic-progenitor-differentiation
#4
Carol M Collins, Joseph Ellis, James M Holaska
Mutations in the gene encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD). Emerin is an integral inner nuclear membrane protein and a component of the nuclear lamina. EDMD is characterized by skeletal muscle wasting, cardiac conduction defects and tendon contractures. The failure to regenerate skeletal muscle is predicted to contribute to the skeletal muscle pathology of EDMD. We hypothesize muscle regeneration defects are caused by impaired muscle stem cell differentiation. Myogenic progenitors derived from emerin-null mice were used to confirm their impaired differentiation and analyze selected myogenic molecular pathways...
February 10, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28183735/new-insights-into-the-regulatory-function-of-cyfip1-in-the-context-of-wave-and-fmrp-containing-complexes
#5
Sabiha Abekhoukh, H Bahar Sahin, Mauro Grossi, Samantha Zongaro, Thomas Maurin, Irene Madrigal, Daniele Kazue-Sugioka, Annick Raas-Rothschild, Mohamed Doulazmi, Pilar Carrera, Andrea Stachon, Steven Scherer, Maria Rita Drula Do Nascimento, Alain Trembleau, Ignacio Arroyo, Szatmari Peter, Isabel M Smith, Montserrat Milà, Adam C Smith, Angela Giangrande, Isabelle Caillé, Barbara Bardoni
CYtoplasmic FMRP Interacting Protein 1 (CYFIP1) is a candidate gene for intellectual disability (ID), autism, schizophrenia and epilepsy. It is a member of a family of proteins that is very conserved during evolution, sharing high homology with dCYFIP, its Drosophila homolog. CYFIP1 interacts with the Fragile X Mental Retardation Protein (FMRP), whose absence causes the Fragile X Syndrome, and with the translation initiation factor eIF4E. It is a member of the WAVE Regulatory Complex (WRC), thus representing a link between translational regulation and actin cytoskeleton...
February 9, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28167616/towards-trans-diagnostic-mechanisms-in-psychiatry-neurobehavioral-profile-of-rats-with-a-loss-of-function-point-mutation-in-the-dopamine-transporter-gene
#6
Valentina Vengeliene, Anton Bespalov, Martin Roßmanith, Sandra Horschitz, Stefan Berger, Ana L Relo, Hamid R Noori, Peggy Schneider, Thomas Enkel, Dusan Bartsch, Miriam Schneider, Berthold Behl, Anita C Hansson, Patrick Schloss, Rainer Spanagel
The Research Domain Criteria (RDoC) matrix has been developed to reorient psychiatric research towards measurable behavioral dimensions and underlying mechanisms. Here we used a new genetic rat model with a loss of function point mutation in the dopamine transporter (DAT) gene (Slc6a3_N157K) to systematically study the RDoC matrix (www.nimh.nih.gov/research-priorities/rdoc/constructs/rdoc-matrix.shtml). First, we examined the impact of the Slc6a3_N157K mutation on monoaminergic signaling. We then performed behavioral tests representing each of the five RDoC domains - negative and positive valence systems, cognitive, social, and in arousal/regulatory systems...
February 6, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28167615/the-familial-dysautonomia-disease-gene-ikbkap-elp1-is-required-in-the-developing-and-adult-central-nervous-system
#7
Marta Chaverra, Lynn George, Marc Mergy, Hannah Waller, Katharine Kujawa, Connor Murnion, Ezekiel Sharples, Julian Thorne, Nathaniel Podgajny, Andrea Grindeland, Yumi Ueki, Steven Eiger, Cassie Cusick, A Michael Babcock, George A Carlson, Frances Lefcort
Hereditary sensory and autonomic neuropathies (HSANs) are a genetically and clinically diverse group of disorders defined by peripheral nervous system (PNS) dysfunction. HSAN Type III, Familial Dysautonomia (FD), results from a single base mutation in the gene IKBKAP that encodes a scaffolding unit for a multi-subunit complex Elongator. Since mutations in other Elongator subunits (ELP2-4) are associated with central nervous system (CNS) disorders, the goal of this study was to investigate a potential CNS requirement for Ikbkap/Elp1 The sensory and autonomic pathophysiology of FD is fatal, with the majority of patients dying by age 40...
February 6, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28153846/miconazole-protects-blood-vessels-from-matrix-metalloproteinase-9-dependent-rupture-and-hemorrhage
#8
Ran Yang, Yunpei Zhang, Dandan Huang, Xiao Luo, Liangren Zhang, Xiaojun Zhu, Xiaolin Zhang, Zhenming Liu, Jingyan Han, Jing-Wei Xiong
Hemorrhagic stroke accounts for 10-15% of all strokes and is strongly associated with mortality and morbidity worldwide, but its prevention and therapeutic interventions remain a major challenge. Here, we report the identification of miconazole as a hemorrhagic suppressor by a small-molecule screen in zebrafish. We found that a hypomorphic mutant fn40a, one of known β-pix mutant alleles in zebrafish, had the major symptoms of brain hemorrhage, vessel rupture, and inflammation as those in hemorrhagic stroke patients...
February 2, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28138096/ptf1a-ela3l-cells-are-developmentally-maintained-progenitors-for-exocrine-regeneration-following-extreme-loss-of-acinar-cells-in-zebrafish-larvae
#9
Nicole Schmitner, Kenji Kohno, Dirk Meyer
The exocrine pancreas displays a significant capacity for regeneration and renewal. In humans and mammalian model systems, the partial loss of exocrine tissue, such as after acute pancreatitis or partial pancreatectomy induces rapid recovery via expansion of surviving acinar cells. In mouse it was further found that an almost complete removal of acinar cells initiates regeneration from a currently not well-defined progenitor pool. Here we used the zebrafish as an alternative model to study cellular mechanisms of exocrine regeneration following an almost complete removal of acinar cells...
January 30, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28138095/long-lasting-memory-deficits-in-mice-withdrawn-from-cocaine-are-concomitant-to-neuroadaptations-in-hippocampal-basal-activity-gabaergic-interneurons-and-adult-neurogenesis
#10
David Ladrón de Guevara-Miranda, Carmelo Millón, Cristina Rosell-Valle, Mercedes Pérez-Fernández, Michele Missiroli, Antonia Serrano, Francisco J Pavón, Fernando Rodríguez de Fonseca, Magdalena Martínez-Losa, Manuel Álvarez-Dolado, Luis J Santín, Estela Castilla-Ortega
The cocaine addiction disorder is notably aggravated by concomitant cognitive and emotional pathology that impedes recovery. We studied whether a persistent cognitive/emotional dysregulation in mice withdrawn from cocaine holds a neurobiological correlate within the hippocampus, a limbic region with a key role in anxiety and memory but that has been scarcely investigated in cocaine addiction research. Mice were submitted to a chronic cocaine (20 mg/kg/day for 12 days) or vehicle treatment followed by 44 drug-free days...
January 30, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28130355/2intestinal-epithelial-cell-caveolin-1-regulates-fatty-acid-and-lipoprotein-cholesterol-plasma-levels
#11
Jessica P Otis, Meng-Chieh Shen, Vanessa Quinlivan, Jennifer L Anderson, Steven A Farber
Caveolae and their structural protein caveolin 1 (CAV1) have roles in cellular lipid processing and systemic lipid metabolism. Global deletion of CAV1 in mice results in insulin resistance and increases in atherogenic plasma lipids and cholesterol, but protects from diet-induced obesity and atherosclerosis. Despite the fundamental role of the intestinal epithelia in the regulation of dietary lipid processing and metabolism, the contributions of CAV1 to lipid metabolism in this tissue have never been directly investigated...
January 26, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28130354/genetic-physiological-and-comparative-genomic-studies-of-hypertension-and-insulin-resistance-in-the-spontaneously-hypertensive-rat
#12
Philip M Coan, Oliver Hummel, Ana Isabel Garcia Diaz, Marjorie Barrier, Neza Alfazema, Penny J Norsworthy, Michal Pravenec, Enrico Petretto, Norbert Huebner, Timothy J Aitman
We previously mapped hypertension-related insulin resistance quantitative trait loci (QTL) to rat chromosomes 4, 12 and 16 using adipocytes from F2 crosses between spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and subsequently identified Cd36 as the gene underlying the chromosome 4 locus. The identity of the chromosome 12 and 16 genes remains unknown. To identify whole body phenotypes associated with the chromosome 12 and 16 linkage regions, we generated and characterised new congenic strains, with WKY donor segments introgressed onto an SHR genetic background, for the chromosome 12 and 16 linkage regions...
January 26, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28130353/gene-expression-profiles-among-murine-strains-segregate-with-distinct-differences-in-the-progression-of-radiation-induced-lung-disease
#13
Isabel L Jackson, Fitsum Baye, Chirayu P Goswami, Barry P Katz, Andrew Zodda, Radmila Pavlovic, Ganga Gurung, Don Winans, Zeljko Vujaskovic
Molecular mechanisms underlying development of acute pneumonitis and/or late fibrosis following thoracic irradiation remain poorly understood. Here we hypothesize that heterogeneity in disease progression and phenotypic expression of radiation-induced lung disease (RILD) across murine strains presents an opportunity to better elucidate mechanisms driving tissue response toward pneumonitis and/or fibrosis. In this study distinct differences in disease progression were observed in age- and sex-matched CBA/J, C57L/J, and C57BL/6J mice over 1 y after graded doses of whole-thorax lung irradiation (WTLI)...
January 26, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28108469/blood-rna-biomarkers-in-prodromal-park4-and-rem-sleep-behavior-disorder-show-role-of-complexin-1-loss-for-risk-of-parkinson-s-disease
#14
Suna Lahut, Suzana Gispert, Özgür Ömür, Candan Depboylu, Kay Seidel, Jorge Antolio Domínguez-Bautista, Nadine Brehm, Hülya Tireli, Karl Hackmann, Caroline Pirkevi, Barbara Leube, Vincent Ries, Kerstin Reim, Nils Brose, Wilfred F den Dunnen, Madrid Johnson, Zsuzsanna Wolf, Marc Schindewolf, Wiebke Schrempf, Kathrin Reetz, Peter Young, David Vadasz, Achilleas S Frangakis, Evelin Schröck, Helmuth Steinmetz, Marina Jendrach, Udo Rüb, Ayşe Nazlı Başak, Wolfgang Oertel, Georg Auburger
Parkinson's disease (PD) is a frequent neurodegenerative process at old age. Accumulation and aggregation of the lipid-binding SNARE complex component alpha-synuclein (SNCA) underlies this vulnerability and defines stages of disease progression. Determinants of SNCA levels and mechanisms of SNCA neurotoxicity are intensely investigated. In view of physiological SNCA roles in blood to modulate vesicle release, we studied blood samples from a new large pedigree with SNCA gene duplication (PARK4 mutation), to identify effects of SNCA gain-of-function as potential disease biomarkers...
January 20, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28100513/loss-of-ranbp2-in-motor-neurons-causes-the-disruption-of-nucleocytoplasmic-and-chemokine-signaling-and-proteostasis-of-hnrnph3-and-mmp28-and-the-development-of-amyotrophic-lateral-sclerosis-als-like-syndromes
#15
Kyoung-In Cho, Dosuk Yoon, Sunny Qiu, Zachary Danziger, Warren M Grill, William C Wetsel, Paulo A Ferreira
The pathogenic drivers of sporadic and familial motor neuron disease (MND), such ALS, are unknown. MND impair the Ran GTPase cycle, which controls nucleocytoplasmic transport, ribostasis and proteostasis; however, cause-effect mechanisms of Ran GTPase modulators in motoneuron pathobiology are heretofore elusive. The cytosolic and peripheral nucleoporin, Ranbp2, is a critical regulator of the Ran GTPase cycle and proteostasis of neurological disease-prone substrates, but the roles of Ranbp2 in motoneuron biology and disease remain unknown...
January 18, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28093508/vertical-sleeve-gastrectomy-reduces-blood-pressure-and-hypothalamic-endoplasmic-reticulum-stress-in-mice
#16
Anne K McGavigan, Zachariah M Henseler, Darline Garibay, Scott D Butler, Sisitha Jayasinghe, Ruth E Ley, Robin L Davisson, Bethany P Cummings
Bariatric surgery, such as vertical sleeve gastrectomy (VSG), causes remarkable improvements in cardiometabolic health, including hypertension remission. However, the mechanisms responsible remain undefined and poorly studied. Therefore, we developed and validated the first murine model of VSG that recapitulates the blood pressure lowering effect of VSG using gold-standard radiotelemetry technology. We used this model to investigate several potential mechanisms, including body weight, brain endoplasmic reticulum (ER) stress signaling and brain inflammatory signaling, all critical contributors to obesity-associated hypertension pathogenesis...
January 12, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28093507/mosaic-expression-of-atrx-in-the-central-nervous-system-causes-memory-deficits
#17
Renee J Tamming, Jennifer R Siu, Yan Jiang, Marco A M Prado, Frank Beier, Nathalie G Bérubé
The rapid modulation of chromatin organization is thought to play a critical role in cognitive processes such as memory consolidation. This is supported in part by the dysregulation of many chromatin remodeling proteins in neurodevelopmental and psychiatric disorders. A key example is ATRX, an X-linked gene commonly mutated in individuals with syndromic and non-syndromic intellectual disability (ID). The consequences of Atrx inactivation on learning and memory have been difficult to evaluate due to the early lethality of hemizygous-null animals...
January 12, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28093506/the-tyrosine-kinase-receptor-tyro3-enhances-lifespan-and-neuropeptide-y-npy-neuron-survival-in-the-mouse-anorexia-anx-mutation
#18
Dennis Y Kim, Joanna Yu, Ryan K Mui, Rieko Niibori, Hamza Bin Taufique, Rukhsana Aslam, John W Semple, Sabine P Cordes
Severe appetite and weight loss define the eating disorder anorexia nervosa, and can also accompany the progression of some neurodegenerative disorders, such as amyotrophic lateral scelerosis (ALS). While acute loss of hypothalamic neurons that produce appetite-stimulating neuropeptide Y (Npy) and agouti related peptide (AgRP) in adult mice or in mice homozygous for the anorexia (anx) mutation causes aphagia, our understanding of the factors that help maintain appetite regulatory circuitry is limited. Here we identify a mutation that converts an arginine to a tryptophan (R7W) in the Tyrosine receptor kinase 3 (Tyro3) gene, which resides within the anx critical interval, as contributing to the severity of anx phenotypes...
January 12, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28093505/modelling-the-ferrochelatase-c-315-48c-modifier-mutation-for-erythropoietic-protoporphyria-epp-in-mice
#19
Jasmin Barman-Aksözen, Paulina Ćwiek, Vijay B Bansode, Frank Koentgen, Judith Trüb, Pawel Pelczar, Paolo Cinelli, Xiaoye Schneider-Yin, Daniel Schümperli, Elisabeth I Minder
Erythropoietic Protoporphyria (EPP) is caused by deficiency of ferrochelatase (FECH) which incorporates iron into protoporphyrin IX (PPIX) to form heme. Excitation of accumulated PPIX by light generates oxygen radicals which evoke excessive pain and, after longer light exposure, ulcerations in exposed skin areas of EPP patients. Moreover, ∼5% of the patients develop a liver dysfunction due to PPIX accumulation. Most patients (∼97%) have a severe FECH mutation (Mut) in trans to an intronic polymorphism (c...
January 12, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28093504/a-model-of-type-2-diabetes-in-the-guinea-pig-using-sequential-diet-induced-glucose-intolerance-and-streptozotocin-treatment
#20
Brendan K Podell, David F Ackart, Michael A Richardson, James E DiLisio, Bruce Pulford, Randall J Basaraba
Type 2 diabetes is a leading cause of morbidity and mortality among non-communicable diseases and additional animal models that more closely replicate the pathogenesis of human type 2 diabetes are needed. The goal of this study was to develop a model of type 2 diabetes in guinea pigs in which diet-induced glucose intolerance precedes β cell cytotoxicity, two processes that are critical to the development of human type 2 diabetes. Guinea pigs developed impaired glucose tolerance after eight weeks of feeding a high fat, high carbohydrate diet, as determined by oral glucose challenge...
January 12, 2017: Disease Models & Mechanisms
journal
journal
42139
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"