Summary: This final installment of a two-part Review discusses how cycles of dedifferentiation and redifferentiation can promote tumorigenesis in the skin and intestine, showing how plasticity in these continuously renewing tissues might contribute to tumorigenesis.
The relationship between sex hormones, the vaginal microbiome and immunity in HIV-1 susceptibility in women
Summary: A better understanding of the sex-hormone–microbiome–immunity axis can provide key information about the determinants of HIV-1 susceptibility in the female genital tract and consequently inform HIV-1 prevention strategies.
Summary: Using random germline mutagenesis and screening of mice, we determined that loss of MYO1D function in nonhematopoietic tissues renders mice susceptible to colitis induced by dextran sodium sulfate challenge.
Studying the differential efficacy of postsymptom antitoxin treatment in type A versus type B botulism using a rabbit spirometry model
Summary: Here, we used a quantitative rabbit respiratory model to study the human-related, differential antitoxin efficacy observed in type A and type B botulism.
Correction of cognitive deficits in mouse models of Down syndrome by a pharmacological inhibitor of DYRK1A
Summary: Normalization of DYRK1A kinase activity can be achieved in three different mouse models of Down syndrome with pharmacological inhibitors of DYRK1A, leading to correction of recognition memory deficits.
A nonalcoholic fatty liver disease model in human induced pluripotent stem cell-derived hepatocytes, created by endoplasmic reticulum stress-induced steatosis
Summary: Our study demonstrates expanded use of human induced pluripotent stem cell-derived hepatocytes for molecular studies and drug screening, to evaluate new therapeutics with an antisteatotic mechanism of action for nonalcoholic fatty liver disease.
Summary: Development of new model systems with which to evaluate cellular responses to compression enables experimental modeling of the intraperitoneal force environment of ovarian cancer patients with tense ascites.
Aberrant cerebellar Purkinje cell activity as the cause of motor attacks in a mouse model of episodic ataxia type 2
Summary: Here, we report that in the well-established mouse model of episodic ataxia type 2, tottering, the severe episodic motor signs are caused by highly erratic activity of Purkinje cells.
Soluble endoglin regulates expression of angiogenesis-related proteins and induction of arteriovenous malformations in a mouse model of hereditary hemorrhagic telangiectasia
Summary: Soluble endoglin regulates vascular development and arteriovenous malformations by modulating angiogenesis, and its effect on endothelial cells depends on expression of endogenous membrane-bound endoglin.
A Drosophila model of combined D-2- and L-2-hydroxyglutaric aciduria reveals a mechanism linking mitochondrial citrate export with oncometabolite accumulation
Summary: This study reveals a mechanism that links export of mitochondrial citrate to accumulation of the oncometabolite L-2-hydroxyglutarate, suggesting a potential treatment for individuals with combined D-2- and L-2-hydroxyglutaric aciduria, a rare inborn error of metabolism.
Summary: Strumpellin, a core member of the WASH complex, plays a key role in the endolysosomal system. Deficiencies in endo-/exocytosis and lysosome morphology are caused by the N471D strumpellin mutation, which is associated with spastic paraplegia 8.
Effects of genetic deletion versus pharmacological blockade of the LPA1 receptor on depression-like behaviour and related brain functional activity
Summary: Animal models of psychopathology are useful for studying the neurobiology of depression. Here, we have assessed by pharmacological approach and knockout models the contribution of the LPA-LPA1 signalling pathway to anxious depression.
Summary: Long and short isoforms of spastin (SPG4) harboring the same missense mutation show different intracellular localization, resistance to pharmacological treatments and effects on axonal cargo transport.
Immunomodulation with minocycline rescues retinal degeneration in juvenile neuronal ceroid lipofuscinosis mice highly susceptible to light damage
Summary: Here, we established a light-damage paradigm to model retinal degeneration in the juvenile neuronal ceroid lipofuscinosis mouse and showed the beneficial effects of minocycline on retinal pathology.
Independent effects of dietary fat and sucrose content on chondrocyte metabolism and osteoarthritis pathology in mice
Summary: The contribution of metabolic factors to obesity-associated knee osteoarthritis is uncertain. Here, we show how dietary fat and sucrose independently alter cartilage metabolic enzymes and osteoarthritis pathophysiology in mice.
Idebenone and coenzyme Q10 are novel PPARα/γ ligands, with potential for treatment of fatty liver diseases
Summary: A zebrafish screen identifies a novel PPARα/γ ligand, idebenone, with potential for treatment of fatty liver diseases, as seen by testing it in a mouse model of type 2 diabetes.
Summary: The authors introduce a new and reliable enthesitis model triggered by innate immune cells and establish multimodal imaging for dynamically assessing inflammation, tissue perfusion and bone remodelling in vivo.
Tbx1 represses Mef2c gene expression and is correlated with histone 3 deacetylation of the anterior heart field enhancer
Summary: Using three experimental models, we demonstrate that Tbx1 suppresses Mef2c gene expression, and show that histone 3 acetylation of the anterior heart field enhancer of the Mef2c gene responds negatively to Tbx1 dosage.
RERE deficiency leads to decreased expression of GATA4 and the development of ventricular septal defects
Summary: In the developing atrioventricular canal, RERE promotes endothelial-to-mesenchymal transition and mesenchymal cell proliferation by positively regulating Gata4. Tissue-specific ablation of Rere in the endocardium causes ventricular septal defects.
Zoledronic acid prevents pagetic-like lesions and accelerated bone loss in the p62P394L mouse model of Paget's disease
Summary: We show that age-related increased osteoclastogenesis is potentiated by the p62 P394L mutation, which allows for development of pagetic-like lesions that progress with ageing, but are prevented by zoledronic acid.
Summary: We developed an orthotopic breast cancer model in mice to monitor, by intravital microscopy, the transitions between collective and single cell invasion and their differential stromal interaction and actin dynamics.
Diacylglycerol kinase (DGKA) regulates the effect of the epilepsy and bipolar disorder treatment valproic acid in Dictyostelium discoideum
Editor's choice: Here, using a tractable model system, Dictyostelium discoideum, we show that diacylglycerol kinase activity might contribute to the cellular mechanism of action of the epilepsy and bipolar disorder treatment, valproic acid.
Summary: A new mouse model has been established that exhibits characteristics of human age-related macular degeneration; the model will facilitate further studies of AMD disease mechanisms.
Summary: Combining exposure to the human carcinogen cadmium with in silico and proteomic top-down approaches, we disclosed the conserved function of two novel tumor suppressor genes in planarian.
Modeling Niemann-Pick disease type C1 in zebrafish: a robust platform for in vivo screening of candidate therapeutic compounds
Summary: A zebrafish genetic model of Niemann-Pick disease type C1 is suitable for performing in vivo screening of candidate therapeutic compounds by examining LysoTracker staining intensity in neuromasts.
Summary: Here, we developed Transgene Electroporation in Adult Zebrafish (TEAZ), a method that enables researchers to study cancer and metastasis by introducing DNA elements focally into somatic adult tissue.
Summary: Here, we describe a new experimental tool to assess contractility of the isolated zebrafish heart perfused in a Langendorff-like system, which will facilitate using zebrafish as a model for human cardiomyopathies.