Read by QxMD icon Read

Disease Models & Mechanisms

Elise L Donovan, Erika Barboza Prado Lopes, Albert Batushansky, Mike Kinter, Timothy M Griffin
Obesity is one of the most significant risk factors of knee osteoarthritis. However, therapeutic strategies to prevent or treat obesity-associated osteoarthritis are limited because of uncertainty about the etiology of disease, particularly with regard to metabolic factors. High-fat diet-induced obese mice have become a widely used model for testing hypotheses about how obesity increases the risk of osteoarthritis, but progress has been limited by variation in disease severity, with some reports concluding that dietary treatment alone is insufficient to induce osteoarthritis in mice...
July 16, 2018: Disease Models & Mechanisms
Hong Zhang, Alexey V Dvornikov, Inken G Huttner, Xiao Ma, Celine F Santiago, Diane Fatkin, Xiaolei Xu
Zebrafish are increasingly used as a vertebrate model to study human cardiovascular disorders. Although heart structure and function are readily visualized in zebrafish embryos because of their optical transparency, the lack of effective tools for evaluating the hearts of older, nontransparent fish has been a major limiting factor. The recent development of high-frequency echocardiography has been an important advance for in vivo cardiac assessment, but it necessitates anesthesia and has limited ability to study acute interventions...
July 16, 2018: Disease Models & Mechanisms
Olga Ilina, Leonard Campanello, Pavel G Gritsenko, Manon Vullings, Chenlu Wang, Peter Bult, Wolfgang Losert, Peter Friedl
Cancer invasion programs are adaptive by switching between metastatic collective and single-cell dissemination, however current intravital microscopy models for epithelial cancer in mice fail to reliably recreate such invasion plasticity. Using image-guided microimplantation of breast cancer spheroids into the murine mammary fat pad and live-cell monitoring, we show microenvironmental conditions and cytoskeletal adaptation during collective to single-cell transition in vivo E-cadherin expressing 4T1 and E-cadherin negative MMT tumors both initiated collective invasion along stromal structures, reflecting invasion patterns in 3D organotypic culture and human primary ductal and lobular carcinoma...
July 11, 2018: Disease Models & Mechanisms
Andromeda Van Roten, Amal Zohir Abo-Zeid Barakat, Annelies Wouters, Thao Anh Tran, Stijn Mouton, Jean-Paul Noben, Luca Gentile, Karen Smeets
Planarians have been long known for their regenerative ability, which hinges on pluripotency. Recently, however, the planarian model has been successfully established for routine toxicological screens aimed to assess over-proliferation, mutagenicity and tumorigenesis. In this study, we focused on planarian tumor suppressor genes (TSGs) and their role during chemically-induced carcinogenic stress in Schmidtea mediterranea Combining in silico and proteomic screens to the exposure to human carcinogen type 1A agent cadmium (Cd), we showed that many TSGs have a function in stem cells and that, in general, the exposure to Cd accelerated the onset and increased the severity of the observed phenotype...
July 2, 2018: Disease Models & Mechanisms
Young-Eun Kim, Minji Lee, Hyejung Gu, Jeongwoo Kim, Seongju Jeong, Sujin Yeo, You Jeong Lee, Sin-Hyeog Im, Young-Chul Sung, Hak Jae Kim, Irving L Weissman, G-One Ahn
Inflammatory bowel disease (IBD) is a chronic inflammatory disease where the intestinal epithelium loses its barrier function. Given the existence of the oxygen gradient in the intestinal epithelium and that inflammation further contributes to the tissue hypoxia, we investigated a role of hypoxia-inducible factor (HIF), a transcription factor activated under hypoxic conditions in myeloid cells in the progression of IBD. To do this, we utilized myeloid-specific knockout (KO) mice targeting HIF pathways created by Cre-loxP system with human MRP8 (hMRP8), an intracellular calcium binding protein as the myeloid promoter...
July 2, 2018: Disease Models & Mechanisms
Yumi Ueki, Veronika Shchepetkina, Frances Lefcort
Familial dysautonomia (FD) is an autosomal recessive disorder marked by developmental and progressive neuropathies. It is caused by an intronic point mutation in the inhibitor of kappa B kinase complex-associated protein (IKAP, also called ELP1) gene IKBKAP/ELP1 , a component of the Elongator complex. Due to variation in tissue-specific splicing, the mutation primarily affects the nervous system. One of the most debilitating hallmarks of FD that affects patients' quality of life is progressive blindness. To determine the pathophysiological mechanisms that are triggered by the absence of IKAP in the retina, we generated retina-specific Ikbkap conditional knockout (CKO) mice using a Pax6-Cre , which abolished Ikbkap expression in all the cell types of the retina...
June 21, 2018: Disease Models & Mechanisms
Meng Zhang, Yi Chu, Joseph Mowery, Brandon Konkel, Susana Galli, Alexander C Theos, Nady Golestaneh
Age-related macular degeneration (AMD) is the major cause of blindness in the elderly in developed countries and its prevalence is increasing with the aging population. AMD initially affects the retinal pigment epithelium (RPE) and gradually leads to secondary photoreceptor degeneration. Recent studies have associated mitochondrial damage with AMD, and we have observed mitochondrial and autophagic dysfunction and repressed peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α in native RPE from AMD donor eyes and their respective induced pluripotent stem cell-derived RPE (AMD RPE-iPSC-RPE)...
June 20, 2018: Disease Models & Mechanisms
Nelly El-Sakkary, Steven Chen, Michelle R Arkin, Conor R Caffrey, Paula Ribeiro
Schistosomiasis is a tropical disease caused by a flatworm trematode parasite that infects over 240 million people worldwide. Treatment and control of the disease rely on just one drug, praziquantel. The possibility of drug resistance coupled with praziquantel's variable efficacy encourages the identification of new drugs and drug targets. Disruption of neuromuscular homeostasis in parasitic worms is a validated strategy for drug development. However, in schistosomes, much remains to be understood about the organization of the nervous system, its component neurotransmitters and potential for drug discovery...
June 20, 2018: Disease Models & Mechanisms
Derek J Erstad, Mozhdeh Sojoodi, Martin S Taylor, Sarani Ghoshal, Allen A Razavi, Katherine A Graham-O'Regan, Nabeel Bardeesy, Cristina R Ferrone, Michael Lanuti, Peter Caravan, Kenneth K Tanabe, Bryan C Fuchs
INTRODUCTION: Syngeneic, immunocompetent allograft tumor models recapitulate important aspects of the tumor microenvironment and have short tumor latency with predictable growth kinetics, making them useful for trialing novel therapeutics. We describe surgical techniques for orthotopic and heterotopic PDAC tumor implantation and characterize phenotypes based on implantation site. METHODS: Mice (n=8 per group) were implanted with 104 cells in the pancreas or flank...
June 14, 2018: Disease Models & Mechanisms
Ricardo Mondragon-Gonzalez, Rita C R Perlingeiro
Myotonic Dystrophy 1 (DM1) is a multi-system disorder primarily affecting the central nervous system, heart and skeletal muscle. It is caused by an expansion of the CTG trinucleotide repeats in the 3' untranslated region of the DMPK gene. Although patient myoblasts have been used for studying the disease in vitro , the invasiveness as well as the low accessibility to muscle biopsies motivate the development of alternative reliable myogenic models. Here, we established two DM1 iPS cell lines from patient-derived fibroblasts, and using the PAX7 conditional expression system, differentiated these into myogenic progenitors, and subsequently, terminally differentiated myotubes...
June 13, 2018: Disease Models & Mechanisms
Amandine Palandri, Elodie Martin, Maria Russi, Michael Rera, Hervé Tricoire, Véronique Monnier
Friedreich's ataxia (FA) is caused by reduced levels of frataxin, a highly conserved mitochondrial protein. There is currently no effective treatment for this disease, characterized by progressive neurodegeneration and cardiomyopathy, the latter being the most common cause of death in patients. We previously developed a Drosophila melanogaster cardiac model of FA, in which the fly frataxin is inactivated specifically in the heart, leading to heart dilatation and impaired systolic function. Methylene Blue (MB) was highly efficient to prevent these cardiac dysfunctions...
June 13, 2018: Disease Models & Mechanisms
Eric D Spear, Erh-Ting Hsu, Laiyin Nie, Elisabeth P Carpenter, Christine A Hrycyna, Susan Michaelis
The human zinc metalloprotease ZMPSTE24 is an integral membrane protein critical for the final step in the biogenesis of the nuclear scaffold protein lamin A, encoded by LMNA After farnesylation and carboxyl methylation of its C-terminal CAAX motif, the lamin A precursor, prelamin A, undergoes proteolytic removal of its modified C-terminal 15 amino acids by ZMPSTE24. Mutations in LMNA or ZMPSTE24 that impede this prelamin A cleavage step cause the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS) and the related progeroid disorders mandibuloacral dysplasia-type B (MAD-B) and restrictive dermopathy (RD)...
May 29, 2018: Disease Models & Mechanisms
Soo-Hyun Kim, Richard P Redvers, Lap Hing Chi, Xiawei Ling, Andrew J Lucke, Robert C Reid, David P Fairlie, Ana Carolina Baptista Moreno Martin, Robin L Anderson, Delphine Denoyer, Normand Pouliot
Breast cancer brain metastasis remains largely incurable. While several mouse models have been developed to investigate the genes and mechanisms regulating breast cancer brain metastasis, these models often lack clinical relevance since they require the use of immune-compromised mice and/or are poorly metastatic to brain from the mammary gland. We describe the development and characterisation of an aggressive brain metastatic variant of the 4T1 syngeneic model (4T1Br4) that spontaneously metastasises to multiple organs, but is selectively more metastatic to the brain from the mammary gland than parental 4T1 tumours...
May 21, 2018: Disease Models & Mechanisms
Kerstin W Sinkevicius, Thomas R Morrison, Praveen Kulkarni, Martha K Caffrey Cagliostro, Sade Iriah, Samantha Malmberg, Julia Sabrick, Jennifer A Honeycutt, Kim L Askew, Malav Trivedi, Craig F Ferris
RNASET2 deficiency in humans is associated with infant cystic leukoencephalopathy, which causes psychomotor impairment, spasticity, and epilepsy. A zebrafish mutant model suggests that loss of RNASET2 function leads to neurodegeneration due to the accumulation of non-degraded RNA in the lysosomes. The goal of this study was to characterize the first rodent model of RNASET2 deficiency. The brains of 3- and 12-month-old RNaseT2 knockout rats were studied using multiple magnetic resonance imaging modalities and behavioral tests...
May 10, 2018: Disease Models & Mechanisms
Romain Helleringer, Delphine Le Verger, Xia Li, Charlotte Izabelle, Rémi Chaussenot, Mehdi Belmaati-Cherkaoui, Raoudha Dammak, Paulette Decottignies, Hervé Daniel, Micaela Galante, Cyrille Vaillend
Recent emphasis has been placed on the role that cerebellar dysfunctions could have in the genesis of cognitive deficits in Duchenne muscular dystrophy (DMD). However, relevant genotype-phenotype analyses are missing to define whether cerebellar defects underlie the severe cases of intellectual deficiency that have been associated with genetic loss of the smallest product of the dmd gene, the Dp71 dystrophin. To determine for the first time whether Dp71 loss could affect cerebellar physiology and functions, we have used patch-clamp electrophysiological recordings in acute cerebellar slices and a cerebellum-dependent behavioral test battery addressing cerebellum-dependent motor and non-motor functions in Dp71 - null transgenic mice...
July 10, 2018: Disease Models & Mechanisms
Spencer A Hobson-Gutierrez, Carlos Carmona-Fontaine
The extracellular space of solid tumors ranges from being well-nurtured to being completely ischemic and can serve as a source of intratumoral heterogeneity, determining the behavior and molecular profiles of malignant and stromal cells. Here, we discuss how the metabolic tumor microenvironment modulates the phenotypes of the immune cells that infiltrate tumors, with an emphasis on tumor-associated macrophages. These cells constitute a diverse population that has pro-tumoral and anti-inflammatory properties, and are likened to anti-inflammatory 'M2' macrophages...
July 6, 2018: Disease Models & Mechanisms
Peiwei Huangyang, M Celeste Simon
The study of cellular metabolism has been rigorously revisited over the past decade, especially in the field of cancer research, revealing new insights that expand our understanding of malignancy. Among these insights is the discovery that various metabolic enzymes have surprising activities outside of their established metabolic roles, including in the regulation of gene expression, DNA damage repair, cell cycle progression and apoptosis. Many of these newly identified functions are activated in response to growth factor signaling, nutrient and oxygen availability, and external stress...
July 6, 2018: Disease Models & Mechanisms
Iris Ribitsch, Rupert L Mayer, Monika Egerbacher, Simone Gabner, Maciej M Kańduła, Julie Rosser, Eva Haltmayer, Ulrike Auer, Sinan Gültekin, Johann Huber, Andrea Bileck, David P Kreil, Christopher Gerner, Florien Jenner
Osteoarthritis (OA), a degenerative joint disease characterized by progressive cartilage degeneration, is one of the leading causes of disability worldwide owing to the limited regenerative capacity of adult articular cartilage. Currently, there are no disease-modifying pharmacological or surgical therapies for OA. Fetal mammals, in contrast to adults, are capable of regenerating injured cartilage in the first two trimesters of gestation. A deeper understanding of the properties intrinsic to the response of fetal tissue to injury would allow us to modulate the way in which adult tissue responds to injury...
July 6, 2018: Disease Models & Mechanisms
Elliot J Jokl, Gideon L Hughes, Tobias Cracknell, Mary E Pownall, Gonzalo Blanco
The importance of kyphoscoliosis peptidase (KY) in skeletal muscle physiology has recently been emphasised by the identification of novel human myopathies associated with KY deficiency. Neither the pathogenic mechanism of KY deficiency nor a specific role for KY in muscle function have been established. However, aberrant localisation of filamin C (FLNC) in muscle fibres has been shown in humans and mice with loss-of-function mutations in the KY gene. FLNC turnover has been proposed to be controlled by chaperone-assisted selective autophagy (CASA), a client-specific and tension-induced pathway that is required for muscle maintenance...
July 6, 2018: Disease Models & Mechanisms
Genki Hayashi, Cassandre Labelle-Dumais, Douglas B Gould
Collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) form heterotrimers that constitute a major component of nearly all basement membranes. COL4A1 and COL4A2 mutations cause a multisystem disorder that includes variable cerebrovascular and skeletal muscle manifestations. The pathogenicity of COL4A1 and COL4A2 mutations is generally attributed to impaired secretion into basement membranes. Sodium 4-phenylbutyrate (4PBA) is a US Food and Drug Administration-approved drug that promotes mutant heterotrimer secretion in vitro and in vivo Here, we use different 4PBA treatment paradigms to define therapeutic parameters for preventing cerebrovascular and muscular pathologies in Col4a1 mutant mice...
July 4, 2018: Disease Models & Mechanisms
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"