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https://www.readbyqxmd.com/read/29224244/a-histopathological-classification-system-of-tyr-nrasq61k-murine-melanocytic-lesions-a-reproducible-simplified-classification
#1
Pierre Sohier, Léa Legrand, Zackie Aktary, Christine Grill, Véronique Delmas, Florence Bernex, Edouard Reyes-Gomez, Lionel Larue, Béatrice Vergier
Genetically engineered mouse models offer essential opportunities to investigate the mechanisms of initiation and progression in melanoma. Here we report a new simplified histopathology classification of mouse melanocytic lesions in Tyr::NRASQ61K derived models, using an interactive decision tree that produces homogeneous categories. Reproducibility for this classification system was evaluated on a panel of representative cases of murine melanocytic lesions by pathologists and basic scientists. Reproducibility, measured as inter-rater agreement between evaluators using a modified Fleiss' kappa statistic revealed a very good agreement between observers...
December 10, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29224179/antidiabetic-polypill-improves-central-pathology-and-cognitive-impairment-in-a-mixed-model-of-alzheimer-s-disease-and-type-2-diabetes
#2
Carmen Infante-Garcia, Juan Jose Ramos-Rodriguez, Carmen Hierro-Bujalance, Esperanza Ortegon, Eleanor Pickett, Rosemary Jackson, Fernando Hernandez-Pacho, Tara Spires-Jones, Monica Garcia-Alloza
Type 2 diabetes (T2D) is an important risk factor to suffer dementia, being Alzheimer's disease (AD) as the most common form. Both AD and T2D are closely related to aging and with a growing elderly population it might be of relevance to explore new therapeutic approaches that may slow or prevent central complications associated with metabolic disorders. Therefore, we propose the use of the antidiabetic polypill (PP), a pharmacological cocktail, commonly used by T2D patients that include metformin, aspirin, simvastatin, and an angiotensin-converting enzyme inhibitor...
December 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29224105/nuclear-and-membrane-actions-of-estrogen-receptor-alpha-contribution-to-the-regulation-of-energy-and-glucose-homeostasis
#3
Maeva Guillaume, Alexandra Montagner, Coralie Fontaine, Françoise Lenfant, Jean-François Arnal, Pierre Gourdy
Estrogen receptor alpha (ERα) has been demonstrated to play a key role in reproduction but also to exert numerous functions in nonreproductive tissues. Accordingly, ERα is now recognized as a key regulator of energy homeostasis and glucose metabolism and mediates the protective effects of estrogens against obesity and type 2 diabetes. This chapter attempts to summarize our current understanding of the mechanisms of ERα activation and their involvement in the modulation of energy balance and glucose metabolism...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29224093/sex-effects-at-the-ramparts-nutrient-and-microbe-mediated-regulation-of-the-immune-metabolic-interface
#4
Nyrie Israelian, Jayne S Danska
The relationships between dietary compounds, derivative metabolites, and host metabolism and immunity are controlled by diverse molecular mechanisms. Essential contributions to these dynamics come from the community of microbes (the microbiome) inhabiting the human digestive tract. The composition and function of the microbiome are shaped by available nutrients, and reciprocally, these organisms produce an as yet poorly defined repertoire of molecules that communicate with the epithelial barrier and the mucosal immune system...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29224089/cellular-mechanisms-driving-sex-differences-in-adipose-tissue-biology-and-body-shape-in-humans-and-mouse-models
#5
Kalypso Karastergiou, Susan K Fried
Sex differences in adipose tissue distribution and the metabolic, endocrine, and immune functions of different anatomical fat depots have been described, but they are incompletely documented in the literature. It is becoming increasingly clear that adipose depots serve distinct functions in males and females and have specific physiological roles. However, the mechanisms that regulate the size and function of specific adipose tissues in men and women remain poorly understood. New insights from mouse models have advanced our understanding of depot differences in adipose growth and remodeling via the proliferation and differentiation of adipose progenitors that can expand adipocyte number in the tissue or simply replace dysfunctional older and larger adipocytes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29224015/renal-resistive-index-as-a-novel-indicator-for-renal-complications-in-high-fat-diet-fed-mice
#6
Hairong Xu, Zejun Ma, Shan Lu, Rui Li, Liangkun Lyu, Lexi Ding, Qiulun Lu
BACKGROUND/AIMS: The renal resistive index (RI) is a novel candidate as a renal injury prognostic indicator, but it remains unclear how renal RI levels correspond to renal injury in diabetic nephropathy. METHODS: To examine this issue, we compared 8-week-old male C57BL/6 mice fed with high-fat diet (HFD) versus chow diet (CHD) for 16 weeks. At 8 and 12 weeks, the glomerular filtration rate (GFR), urinary albumin-to-creatinine ratio (UACR), and inflammatory factors (IL-1β, IL-6, TNFα, and MCP-1) were measured, along with the increase in renal RI...
December 7, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29224010/microrna-195-suppresses-the-progression-of-pancreatic-cancer-by-targeting-dclk1
#7
Bin Zhou, Chuandong Sun, Xiao Hu, Hanxiang Zhan, Hao Zou, Yujie Feng, Fabo Qiu, Shun Zhang, Liqun Wu, Bingyuan Zhang
BACKGROUND/AIMS: Doublecortin-like kinase 1 (DCLK1) is emerging as a tumor-specific stem cell marker in pancreatic cancer (PC). MicroRNA-195 (miR-195) plays an important role in many types of tumors. However, the roles of DCLK1 in cancer and miRNAs that directly regulate DCLK1 have not been elucidated. The goal of this study is to assess the effects of miR-195 on inhibiting DCLK1 and to clarify the regulating mechanism of miR-195-DCLK1 in PC cells. METHODS: The expression of DCLK1 protein and miR-195 in PC tissues and adjacent healthy pancreatic tissues was detected by Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively and the correlation between overall survival of PC patients and expression of DCLK1 was measured by Kaplan-Meier analysis...
December 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29223787/a-novel-peptide-based-vaccine-candidate-with-protective-efficacy-against-influenza-a-in-a-mouse-model
#8
José Herrera-Rodriguez, Tjarko Meijerhof, Hubert G Niesters, Grete Stjernholm, Arnt-Ove Hovden, Birger Sørensen, Mats Ökvist, Maja A Sommerfelt, Anke Huckriede
Current influenza vaccines mainly induce antibody responses to the variable hemagglutinin proteins of the virus strains included in the vaccine. Instead, a broadly protective influenza vaccine should aim at inducing antibody- and/or cell-mediated immunity against conserved viral proteins. Vacc-FLU is a peptide based vaccine combining conserved B and T cell epitopes. Peptide selection was done using a proprietary peptide design platform technology focusing on responses to human leukocyte antigen (HLA)-restricted epitopes...
December 7, 2017: Virology
https://www.readbyqxmd.com/read/29223763/dyrk1a-haploinsufficiency-in-mice-causes-autistic-like-features-and-febrile-seizures
#9
Matthieu Raveau, Atsushi Shimohata, Kenji Amano, Hiroyuki Miyamoto, Kazuhiro Yamakawa
Mutations and copy number variants affecting DYRK1A gene encoding the dual-specificity tyrosine phosphorylation-regulated kinase 1A are among the most frequent genetic causes of neurodevelopmental disorders including autism spectrum disorder (ASD) associated with microcephaly, febrile seizures and severe speech acquisition delay. Here we developed a mouse model harboring a frame-shift mutation in Dyrk1a resulting in a protein truncation and elimination of its kinase activity site. Dyrk1a+/- mice showed significant impairments in cognition and cognitive flexibility, communicative ultrasonic vocalizations, and social contacts...
December 6, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29223735/targeting-secreted-cytokine-bmp9-gates-the-attenuation-of-hepatic-fibrosis
#10
Peng Li, Yongyun Li, Liqi Zhu, Zhi Yang, Jie He, Lihua Wang, Qingfeng Shang, Hui Pan, Huixue Wang, Xiong Ma, Bin Li, Xianqun Fan, Shengfang Ge, Renbing Jia, He Zhang
Liver fibrosis is overly exuberant wound healing that leads to portal hypertension or liver cirrhosis. Recent studies have demonstrated the functions of bone morphogenetic protein 9 (BMP9) in liver fibrosis, and thus, targeting liver-specific BMP9 abnormalities will become an attractive approach for developing therapeutics to treat liver fibrosis. Here, we reveal that BMP9 serves as a valuable serum diagnostic indicator and efficient therapeutic target to attenuate liver fibrogenesis. Our analysis of biopsies from liver fibrotic patients revealed that higher BMP9 levels accompanied advanced stages of liver fibrosis...
December 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29223600/trans-%C3%AE%C2%B5-viniferin-is-an-amyloid-%C3%AE-disaggregating-and-anti-inflammatory-drug-in-a-mouse-primary-cellular-model-of-alzheimer-s-disease
#11
Elodie Vion, Guylène Page, Eric Bourdeaud, Marc Paccalin, Jérôme Guillard, Agnès Rioux Bilan
Alzheimer's disease (AD) is marked by several cellular and molecular damage. Therefore, the therapeutic interest of multi-target molecules is increasingly justified. Polyphenols presenting multiple pharmacological effects would be more efficient. In this study, beneficial effects of trans ε-viniferin, a natural polyphenol were thus evaluated. This study reported that this stilbenoid (1) induced the disaggregation of amyloid β (Aβ) peptide and (2) rescued inflammation in murine primary neuronal cultures. These both effects are higher than those of resveratrol, and so, trans ε-viniferin could be a good therapeutic multi-target candidate...
December 6, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29223537/rankl-signaling-sustains-primary-tumor-growth-in-genetically-engineered-mouse-models-of-lung-adenocarcinoma
#12
Julien Faget, Caroline Contat, Nadine Zangger, Solange Peters, Etienne Meylan
HYPOTHESIS: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality. Recent retrospective clinical analyses suggest that blocking the receptor activator of NF-κB (RANK) signaling pathway inhibits the growth of NSCLC and might represent a new treatment strategy. METHODS: RANK and RANKL expression in human lung adenocarcinoma was interrogated from publicly available gene expression datasets. Several genetically engineered mouse models were used to evaluate treatment efficacy of RANK-Fc to block RANKL, with primary tumor growth measured longitudinally using micro-computed tomography...
December 6, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29223395/a-novel-mouse-model-for-tracking-the-fate-of-cxcr5-expressing-t-cells
#13
Tomo Takebe, Kazuki Sakamoto, Yoshikazu Higami, Yohsuke Harada
The germinal center (GC) reaction, a critical process in the humoral immune response, requires follicular helper T (Tfh) cells. Tfh cells express the master transcription factor Bcl6 and chemokine receptor CXCR5, which enable them to migrate from the T cell zone to B cell follicles and interact with GC B cells. However, CXCR5 is downregulated when Tfh cells become memory cells. Therefore, it is difficult to track Tfh cells continuously in vivo. In this study, we generated a mouse strain, Cxcr5CreERT2R26Tomato, in which the fluorescent protein tdTomato is inducibly expressed in CXCR5+ cells by tamoxifen administration...
December 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29223359/in-niemann-pick-c1-mouse-models-glial-only-expression-of-the-normal-gene-extends-survival-much-further-than-do-changes-in-genetic-background-or-treatment-with-hydroxypropyl-beta-cyclodextrin
#14
Craig A Marshall, Dawn E Watkins-Chow, Giampiero Palladino, Gail Deutsch, Keshav Chandran, William J Pavan, Robert P Erickson
The Npc1nmf164 allele of Npc1 provides a mouse model for Niemann-Pick disease type C1 (NPC1), a genetic disease known to have a widely variable phenotype. The transfer of the Npc1nmf164 mutation from the C57BL/6J inbred strain to the BALB/cJ inbred strain increased the mean lifespan from 117.8days to 153.1days, confirming that the severity of the NPC1 phenotype is strongly influenced by genetic background. The transfer of another Npc1 allele, Npc1nih, to this background also extended survival of the homozygotes indicating that the modifying effect of BALB/cJ is not limited to a single allele of Npc1...
December 6, 2017: Gene
https://www.readbyqxmd.com/read/29222989/disrupted-circuits-in-mouse-models-of-autism-spectrum-disorder-and-intellectual-disability
#15
REVIEW
Carla Em Golden, Joseph D Buxbaum, Silvia De Rubeis
Autism spectrum disorder (ASD) and intellectual disability (ID) are caused by a wide range of genetic mutations, a significant fraction of which reside in genes important for synaptic function. Studies have found that sensory, prefrontal, hippocampal, cerebellar, and striatal regions, as well as the circuits that connect them, are perturbed in mouse models of ASD and ID. Dissecting the disruptions in morphology and activity in these neural circuits might help us to understand the shared risk between the two disorders as well as their clinical heterogeneity...
December 5, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29222946/triheptanoin-protects-against-status-epilepticus-induced-hippocampal-mitochondrial-dysfunctions-oxidative-stress-and-neuronal-degeneration
#16
Kah Ni Tan, David Simmons, Catalina Carrasco-Pozo, Karin Borges
Triheptanoin, the triglyceride of heptanoate, is anaplerotic (refills deficient tricarboxylic acid cycle intermediates) via the propionyl-CoA carboxylase (PCC) pathway. It has been shown to be neuroprotective and anticonvulsant in several models of neurological disorders. Here, we investigated the effects of triheptanoin against changes of hippocampal mitochondrial functions, oxidative stress and cell death induced by pilocarpine-induced status epilepticus (SE) in mice. Ten days of triheptanoin pre-treatment did not protect against SE, but it preserved hippocampal mitochondrial functions including state 2, state 3 ADP, state 3 uncoupled respiration, respiration linked to ATP synthesis along with the activities of pyruvate dehydrogenase complex and oxoglutarate dehydrogenase complex 24 h post-SE...
December 9, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29222849/bone-marrow-transplantation-improves-motor-activity-in-a-mouse-model-of-ataxia
#17
David Díaz, Marina Piquer-Gil, Javier Sánchez Recio, María Magdalena Martínez-Losa, José Ramón Alonso, Eduardo Weruaga, Manuel Álvarez-Dolado
Ataxias are locomotor disorders that can have an origin both neural and muscular, although both impairments are related. Unfortunately, ataxia has no cure and the current therapies are aimed at motor re-education or muscular reinforcement. Nevertheless, cell therapy is becoming a promising approach to deal with incurable neural diseases, including neuro-muscular ataxias. Here we have used a model of ataxia, the PCD mutant mouse, to study the effect of healthy (wild-type) bone marrow transplantation on the restoration of defective mobility...
December 8, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29222797/an-in-vivo-compression-model-of-spinal-cord-injury
#18
Irene Paterniti, Emanuela Esposito, Salvatore Cuzzocrea
Animal spinal cord injury (SCI) models have proven highly useful for investigating the mechanisms involved in the injury process and evaluating the effectiveness of experimental therapeutic interventions. Over the last years, substantial improvements have been made in producing consistent and reproducible animal SCI models. Different SCI models have been developed to address the mechanism of injury, being divided into contusion, compression, distraction, dislocation, transection, or chemical models. The method described here is a mouse compression model of SCI that, in many respects, faithfully reproduces SCI in man...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222796/spared-nerve-injury-as-a-long-lasting-model-of-neuropathic-pain
#19
Serena Boccella, Francesca Guida, Enza Palazzo, Ida Marabese, Vito de Novellis, Sabatino Maione, Livio Luongo
This chapter describes surgical procedures for the induction of neuropathic pain using an animal model (rat or mouse) of spared nerve injury. In addition to technical details of the surgical technique, details of anesthesia and perioperative care are also included.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222775/sensory-neurons-from-tau-transgenic-mice-and-their-utility-in-drug-screening
#20
Aviva M Tolkovsky, Jack Brelstaff
Tau misfolding is a major cause of neurodegeneration, tauopathies being a growing group of diseases in which tau forms insoluble aggregates, best known in Alzheimer disease as neurofibrillary tangles (NFTs). Many transgenic mouse models of tauopathies have been generated, but it has been difficult to demonstrate disease in primary brain neurons from these mice because neurons need to be harvested within a few days of birth and tau fails to produce NFTs. Transgenic mice have been generated that express the 0N4R isoform of human tau mutated at amino acid 301 (P301S mice) under the Thy1...
2018: Methods in Molecular Biology
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