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Critical cRe

Jichun Gu, Hexige Saiyin, Deliang Fu, Ji Li
Pancreatic cancer is a uniformly lethal malignancy with an abundant dense desmoplastic stroma. Because of its dense stroma, conventional drugs were considered to not penetrate this physical barrier, and this caused a systemic drug resistance. Thus, abolishing this barrier with targeted agents is considered to improve the efficiency of chemotherapeutic treatment. The Hedgehog (Hh) signaling pathway is a critical regulator of pancreas development and plays diversified roles in pancreatic cancer stroma and neoplastic cells...
April 2018: Pancreas
Alfredo Criollo, Francisco Altamirano, Zully Pedrozo, Gabriele G Schiattarella, Dan L Li, Pablo Rivera-Mejías, Cristian Sotomayor-Flores, Valentina Parra, Elisa Villalobos, Pavan K Battiprolu, Nan Jiang, Herman I May, Eugenia Morselli, Stefan Somlo, Humberto de Smedt, Thomas G Gillette, Sergio Lavandero, Joseph A Hill
AIMS: Considerable evidence points to critical roles of intracellular Ca2+ homeostasis in the modulation and control of autophagic activity. Yet, underlying molecular mechanisms remain unknown. Mutations in the gene (pkd2) encoding polycystin-2 (PC2) are associated with autosomal dominant polycystic kidney disease (ADPKD), the most common inherited nephropathy. PC2 has been associated with impaired Ca2+ handling in cardiomyocytes and indirect evidence suggests that this protein may be involved in autophagic control...
March 5, 2018: Journal of Molecular and Cellular Cardiology
Diego A Miranda, William C Krause, Amaury Cazenave-Gassiot, Miyuki Suzawa, Hazel Escusa, Juat Chin Foo, Diyala S Shihadih, Andreas Stahl, Mark Fitch, Edna Nyangau, Marc Hellerstein, Markus R Wenk, David L Silver, Holly A Ingraham
Excess lipid accumulation is an early signature of nonalcoholic fatty liver disease (NAFLD). Although liver receptor homolog 1 (LRH-1) (encoded by NR5A2) is suppressed in human NAFLD, evidence linking this phospholipid-bound nuclear receptor to hepatic lipid metabolism is lacking. Here, we report an essential role for LRH-1 in hepatic lipid storage and phospholipid composition based on an acute hepatic KO of LRH-1 in adult mice (LRH-1AAV8-Cre mice). Indeed, LRH-1-deficient hepatocytes exhibited large cytosolic lipid droplets and increased triglycerides (TGs)...
March 8, 2018: JCI Insight
Michelle L Stoller, Orvelin Roman, Michael R Deans
The organization of polarized stereociliary bundles is critical for the function of the inner ear sensory receptor hair cells that detect sound and motion, and these cells present a striking example of Planar Cell Polarity (PCP); the coordinated orientation of polarized structures within the plane of an epithelium. PCP is best understood in Drosophila where the essential genes regulating PCP were first discovered, and functions for the core PCP proteins encoded by these genes have been deciphered through phenotypic analysis of core PCP gene mutants...
March 3, 2018: Developmental Biology
Erica Hasten, Donna M McDonald-McGinn, Terrence B Crowley, Elaine Zackai, Beverly S Emanuel, Bernice E Morrow, Silvia E Racedo
Non-allelic homologous recombination events on chromosome 22q11.2 during meiosis can result in either the deletion (22q11.2DS) or duplication (22q11.2DupS) syndrome. Although the spectrum and frequency of congenital heart disease (CHD) are known for 22q11.2DS, there is less known for 22q11.2DupS. We now evaluated cardiac phenotypes in 235 subjects with 22q11.2DupS including 102 subjects we collected and 133 subjects that were previously reported as a confirmation and found 25% have CHD, mostly affecting the cardiac outflow tract (OFT)...
March 2, 2018: Human Molecular Genetics
Tomoko Matsuzaki, Huan Wang, Yukio Imamura, Shunya Kondo, Shuichiro Ogawa, Makoto Noda
Reck encodes a membrane-anchored glycoprotein implicated in the regulation of extracellular metalloproteinases, Notch-signaling, and Wnt7-signaling and shown to play critical roles in embryogenesis and tumor suppression. Precise mechanisms of its actions in vivo, however, remain largely unknown. By homologous recombination, we generated a new Reck allele, ReckCreERT2 (MGI symbol: Reck<tm3.1(cre/ERT2)Noda>). This allele is defective in terms of Reck function but expected to induce loxP-mediated recombination in the cells committed to express Reck...
March 6, 2018: Genesis: the Journal of Genetics and Development
Chenggang Chen, Mingxiu Cheng, Tetsufumi Ito, Sen Song
The inferior colliculus (IC) is a critical integration center in the auditory pathway. However, since the inputs to the IC have typically been studied by the use of conventional anterograde and retrograde tracers, the neuronal organization and cell-type-specific connections in the IC are poorly understood. Here, we utilized monosynaptic rabies tracing and in situ hybridization combined with excitatory and inhibitory Cre transgenic mouse lines of both sexes to characterize the brain-wide and cell-type-specific inputs to specific neuron types within the lemniscal IC core and nonlemniscal IC shell...
February 24, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Lulu Liu, Xiaoling Wan, Peipei Zhou, Xiaoyuan Zhou, Wei Zhang, Xinhui Hui, Xiujie Yuan, Xiaodan Ding, Ruihong Zhu, Guangxun Meng, Hui Xiao, Feng Ma, He Huang, Xianmin Song, Bin Zhou, Sidong Xiong, Yan Zhang
BACKGROUND: Adenosine triphosphate (ATP)-dependent chromatin remodeling SWI/SNF-like BAF and PBAF complexes have been implicated in the regulation of stem cell function and cancers. Several subunits of BAF or PBAF, including BRG1, BAF53a, BAF45a, BAF180, and BAF250a, are known to be involved in hematopoiesis. Baf200, a subunit of PBAF complex, plays a pivotal role in heart morphogenesis and coronary artery angiogenesis. However, little is known on the importance of Baf200 in normal and malignant hematopoiesis...
February 26, 2018: Journal of Hematology & Oncology
Philip Tröster, Julia Haseleu, Jonas Petersen, Oliver Drees, Achim Schmidtko, Frederick Schwaller, Gary R Lewin, Gohar Ter-Avetisyan, York Winter, Stefanie Peters, Susanne Feil, Robert Feil, Fritz G Rathjen, Hannes Schmidt
A cGMP signaling cascade composed of C-type natriuretic peptide, the guanylyl cyclase receptor Npr2 and cGMP-dependent protein kinase I (cGKI) controls the bifurcation of sensory axons upon entering the spinal cord during embryonic development. However, the impact of axon bifurcation on sensory processing in adulthood remains poorly understood. To investigate the functional consequences of impaired axon bifurcation during adult stages we generated conditional mouse mutants of Npr2 and cGKI ( Npr2 fl / fl ;Wnt1 Cre and cGKI KO / fl ;Wnt1 Cre ) that lack sensory axon bifurcation in the absence of additional phenotypes observed in the global knockout mice...
2018: Frontiers in Molecular Neuroscience
Jayne F Martin Carli, Charles A LeDuc, Yiying Zhang, George Stratigopoulos, Rudolph L Leibel
Genetic variants within the FTO (α-ketoglutarate-dependent dioxygenase) gene have been strongly associated with a modest increase in adiposity as a result of increased food intake. These risk alleles are associated with decreased expression of both FTO and neighboring RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein 1 like). RPGRIP1L encodes a protein that is critical to the function of the primary cilium, which conveys extracellular information to the cell. Rpgrip1l+/- mice exhibit increased adiposity, in part, as a result of hyperphagia...
February 21, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Teresa Díaz, Sandy Fillet, Sonia Campoy, Raquel Vázquez, Javier Viña, José Murillo, José L Adrio
Improving the yield of carbohydrate to lipid conversion and lipid productivity are two critical goals to develop an economically feasible process to commercialize microbial oils. Lignocellulosic sugars are potential low-cost carbon sources for this process but their use is limited by the toxic compounds produced during biomass pretreatment at high solids loading, and by the pentose sugars (mainly xylose) which are not efficiently metabolized by many microorganisms. Adaptive laboratory evolution was used to select a Rhodosporidium toruloides strain with robust growth in non-detoxified wheat straw hydrolysates, produced at 20% solids loading, and better xylose consumption rate...
February 20, 2018: Applied Microbiology and Biotechnology
George D Mcilroy, Karla Suchacki, Anke J Roelofs, Wulin Yang, Yanyun Fu, Bo Bai, Robert J Wallace, Cosimo De Bari, William P Cawthorn, Weiping Han, Mirela Delibegović, Justin J Rochford
OBJECTIVE: Mutations to the BSCL2 gene disrupt the protein seipin and cause the most severe form of congenital generalised lipodystrophy (CGL). Affected individuals exhibit a near complete loss of white adipose tissue (WAT) and suffer from metabolic disease. Seipin is critical for adipocyte development in culture and mice with germline disruption to Bscl2 recapitulate the effects of BSCL2 disruption in humans. Here we examined whether loss of Bscl2 specifically in developing adipocytes in vivo is sufficient to prevent adipose tissue development and cause all features observed with congenital BSCL2 disruption...
January 31, 2018: Molecular Metabolism
Mei Chen, Jiawu Zhao, Imran H A Ali, Stephen Marry, Josy Augustine, Mohajeet Bhuckory, Aisling Lynch, Adrien Kissenpfennig, Heping Xu
The suppressor of cytokine signaling protein 3 (SOCS3) critically controls immune cell activation, although its role in macrophage polarization and function remains controversial. Using experimental autoimmune uveoretinitis (EAU) as a model, we show that inflammation-mediated retinal degeneration is exaggerated and retinal angiogenesis is accelerated in mice with SOCS3 deficiency in myeloid cells (LysMCre/+ SOCS3fl/fl ). At the acute stage of EAU, the population of infiltrating neutrophils was increased and the population of macrophages decreased in LysMCre/+ SOCS3fl/fl mice compared with that in wild-type (WT) mice...
February 13, 2018: American Journal of Pathology
Martesa Tantra, Lanboling Guo, Jinsook Kim, Norliyana Zainolabidin, George J Augustine, Volker Eulenburg, Albert I Chen
Inhibitory interneurons mediate the gating of synaptic transmission and modulate the activities of neural circuits. Disruption of the function of inhibitory networks in the forebrain is linked to impairment of social and cognitive behaviors, but the involvement of inhibitory interneurons in the cerebellum has not been assessed. We found that Cadherin 13 (Cdh13), a gene implicated in autism spectrum disorder and attention-deficit hyperactivity disorder, is specifically expressed in Golgi cells within the cerebelluar cortex...
February 15, 2018: Genes, Brain, and Behavior
Y Li, F Zhang, W Lu, X Li
BACKGROUND: Photoreceptor cell death is a key pathology of retinal degeneration diseases. To date, the molecular mechanisms for this pathological process remain largely unclear. Junctional adhesion molecule-c (Jam-c) has been shown to play important roles in different biological events. However, its effect on retinal neuronal cells is unknown. OBJECTIVE: To determine the effect of Jam-c on adult mouse eyes, particularly, on retinal structure, vasculature and photoreceptor cells, in order to explore potential important target molecules for ocular diseases...
February 12, 2018: Current Molecular Medicine
Tomohiko Yoshizawa, Makoto Ito, Kenji Doya
The striatum has been shown to play a critical role in reward prediction. It is composed of two neurochemically and anatomically distinct compartments known as the striosomes and the matrix. The striosomes comprise only about 15% of the striatum by volume and are distributed mosaically therein. Accordingly, it has been difficult to identify striosomal neurons in electrophysiological recordings and it has been unclear whether striosomal neurons, which project to midbrain dopaminergic neurons, engage in reward prediction...
January 2018: ENeuro
Lingyan Zhou, Kunpeng Wu, Liya Zhang, Ling Gao, Shihong Chen
The effect of thyroid-stimulating hormone receptor (TSHR) on hepatic lipid accumulation in vivo is not fully understood. Further, while TSHR in the thyroid has been studied extensively, whether and how the absence of TSHR in the liver affects systemic energy metabolism has not yet been reported. To examine these effects, we generated hepatic TSHR conditional knockout (LT-KO) mice using Cre/LoxP recombination technology. The liver-specific TSHR-knockout (LT-KO) mice exhibited not only lower hepatic triglyceride and cholesterol contents due to modified synthesis and catabolism of lipids in the liver, but also decreased serum lipids, especially serum LDL-C levels...
February 5, 2018: Biochemical and Biophysical Research Communications
Irfana Soomro, Ying Sun, Zhai Li, Lonnette Diggs, Georgia Hatzivassiliou, Ajit G Thomas, Rana Rais, Barbara S Slusher, Stefan Somlo, Edward Y Skolnik
Background: Metabolism of glutamine by glutaminase 1 (GLS1) plays a key role in tumor cell proliferation via the generation of ATP and intermediates required for macromolecular synthesis. We hypothesized that glutamine metabolism also plays a role in proliferation of autosomal-dominant polycystic kidney disease (ADPKD) cells and that inhibiting GLS1 could slow cyst growth in animal models of ADPKD. Methods: Primary normal human kidney and ADPKD human cyst-lining epithelial cells were cultured in the presence or absence of two pharmacologic inhibitors of GLS1, bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide 3 (BPTES) and CB-839, and the effect on proliferation, cyst growth in collagen and activation of downstream signaling pathways were assessed...
February 5, 2018: Nephrology, Dialysis, Transplantation
Carrie R Jonak, Nancy M Lainez, Ulrich Boehm, Djurdjica Coss
Gonadotropin-releasing hormone (GnRH) from the hypothalamus regulates synthesis and secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gonadotropes. LH and FSH are heterodimers, comprised of a common α-subunit and unique β-subunits, which provide biological specificity and are limiting components of the mature hormone synthesis. Gonadotrope cells respond to GnRH via specific expression of the GnRH receptor. GnRH induces the expression of gonadotropin genes and of the GnRH receptor by activation of specific transcription factors...
February 2, 2018: Endocrinology
Lin Cheng, Lucy J Wong, Naihong Yan, Richard C Han, Honghua Yu, Chenying Guo, Khulan Batsuuri, Aniket Zinzuwadia, Ryan Guan, Kin-Sang Cho, Dong Feng Chen
Epigenetic predisposition is thought to critically contribute to adult-onset disorders, such as retinal neurodegeneration. The histone methyltransferase, enhancer of zeste homolog 2 (Ezh2), is transiently expressed in the perinatal retina, particularly enriched in retinal ganglion cells (RGCs). We previously showed that embryonic deletion of Ezh2 from retinal progenitors led to progressive photoreceptor degeneration throughout life, demonstrating a role for embryonic predisposition of Ezh2-mediated repressive mark in maintaining the survival and function of photoreceptors in the adult...
2018: PloS One
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