Read by QxMD icon Read


Gerd Meyer Zu Horste, Dariusz Przybylski, Markus A Schramm, Chao Wang, Alexandra Schnell, Youjin Lee, Raymond Sobel, Aviv Regev, Vijay K Kuchroo
The death receptor Fas removes activated lymphocytes through apoptosis. Previous transcriptional profiling predicted that Fas positively regulates interleukin-17 (IL-17)-producing T helper 17 (Th17) cells. Here, we demonstrate that Fas promoted the generation and stability of Th17 cells and prevented their differentiation into Th1 cells. Mice with T-cell- and Th17-cell-specific deletion of Fas were protected from induced autoimmunity, and Th17 cell differentiation and stability were impaired. Fas-deficient Th17 cells instead developed a Th1-cell-like transcriptional profile, which a new algorithm predicted to depend on STAT1...
March 20, 2018: Immunity
Xin Li, Adeline Gadzinsky, Liying Gong, Haijun Tong, Virginie Calderon, Yue Li, Daisuke Kitamura, Ulf Klein, Wallace Y Langdon, Fajian Hou, Yong-Rui Zou, Hua Gu
Selective expansion of high-affinity antigen-specific B cells in germinal centers (GCs) is a key event in antibody affinity maturation. GC B cells with improved affinity can either continue affinity-driven selection or exit the GC to differentiate into plasma cells (PCs) or memory B cells. Here we found that deleting E3 ubiquitin ligases Cbl and Cbl-b (Cbls) in GC B cells resulted in the early exit of high-affinity antigen-specific B cells from the GC reaction and thus impaired clonal expansion. Cbls were highly expressed in GC light zone (LZ) B cells, where they promoted the ubiquitination and degradation of Irf4, a transcription factor facilitating PC fate choice...
March 20, 2018: Immunity
Hansruedi Mathys, Jay Penney, Li-Huei Tsai
The epigenetic mechanisms controlling microglia functions are largely unknown. In this issue of Immunity, Datta et al. (2018) uncover surprising and distinct effects of deleting the epigenetic regulators HDAC1 and HDAC2 during microglial development versus during the course of neurodegeneration.
March 20, 2018: Immunity
Liansheng Liu, Jinqiu Lu, Xiaoling Li, Ailing Wu, Qingzhe Wu, Mujun Zhao, Nan Tang, Hai Song
Intracellular transport of membranous organelles and protein complexes to various destinations is fundamental to signaling transduction and cellular function. The cytoplasmic dynein motor and its regulatory proteins LIS1 and NDE1 are required for transporting a variety of cellular cargos along the microtubule network. In this study, we show that deletion of Lis1 in developing lung endoderm and limb mesenchymal cells causes agenesis of the lungs and limbs. In both mutants, there is increased cell death and decreased fibroblast growth factor (FGF) signaling activity...
March 20, 2018: Cell Reports
Jennifer F Knight, Vanessa Y C Sung, Elena Kuzmin, Amber L Couzens, Danielle A de Verteuil, Colin D H Ratcliffe, Paula P Coelho, Radia M Johnson, Payman Samavarchi-Tehrani, Tina Gruosso, Harvey W Smith, Wontae Lee, Sadiq M Saleh, Dongmei Zuo, Hong Zhao, Marie-Christine Guiot, Ryan R Davis, Jeffrey P Gregg, Christopher Moraes, Anne-Claude Gingras, Morag Park
Triple-negative breast cancers (TNBCs) display a complex spectrum of mutations and chromosomal aberrations. Chromosome 5q (5q) loss is detected in up to 70% of TNBCs, but little is known regarding the genetic drivers associated with this event. Here, we show somatic deletion of a region syntenic with human 5q33.2-35.3 in a mouse model of TNBC. Mechanistically, we identify KIBRA as a major factor contributing to the effects of 5q loss on tumor growth and metastatic progression. Re-expression of KIBRA impairs metastasis in vivo and inhibits tumorsphere formation by TNBC cells in vitro...
March 20, 2018: Cell Reports
John F Seymour, Thomas J Kipps, Barbara Eichhorst, Peter Hillmen, James D'Rozario, Sarit Assouline, Carolyn Owen, John Gerecitano, Tadeusz Robak, Javier De la Serna, Ulrich Jaeger, Guillaume Cartron, Marco Montillo, Rod Humerickhouse, Elizabeth A Punnoose, Yan Li, Michelle Boyer, Kathryn Humphrey, Mehrdad Mobasher, Arnon P Kater
BACKGROUND: Venetoclax inhibits BCL2, an antiapoptotic protein that is pathologically overexpressed and that is central to the survival of chronic lymphocytic leukemia cells. We evaluated the efficacy of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia. METHODS: In this randomized, open-label, phase 3 trial, we randomly assigned 389 patients to receive venetoclax for up to 2 years (from day 1 of cycle 1) plus rituximab for the first 6 months (venetoclax-rituximab group) or bendamustine plus rituximab for 6 months (bendamustine-rituximab group)...
March 22, 2018: New England Journal of Medicine
Dacheng Ma, Shuguang Peng, Weiren Huang, Zhiming Cai, Zhen Xie
Nuclease dead Cas9 (dCas9) has been widely used for modulating gene expression by fusing with different activation or repression domains. However, delivery of the CRISPR/Cas system fused with variant effector domains in a single adeno-associated virus (AAV) remains challenging due to the payload limit. Here, we engineered a set of downsized variants of Cas9 including Staphylococcus aureus Cas9 (SaCas9) that retained DNA binding activity by deleting conserved functional domains. We demonstrated that fusing FokI nuclease domain to the N-terminal of the minimal SaCas9 (mini-SaCas9) or to the middle of the split mini-SaCas9 can trigger efficient DNA cleavage...
March 21, 2018: ACS Synthetic Biology
Guillaume Huguet, Catherine Schramm, Elise Douard, Lai Jiang, Aurélie Labbe, Frédérique Tihy, Géraldine Mathonnet, Sonia Nizard, Emmanuelle Lemyre, Alexandre Mathieu, Jean-Baptiste Poline, Eva Loth, Roberto Toro, Gunter Schumann, Patricia Conrod, Zdenka Pausova, Celia Greenwood, Tomas Paus, Thomas Bourgeron, Sébastien Jacquemont
Importance;: Copy number variants (CNVs) classified as pathogenic are identified in 10% to 15% of patients referred for neurodevelopmental disorders. However, their effect sizes on cognitive traits measured as a continuum remain mostly unknown because most of them are too rare to be studied individually using association studies. Objective: To measure and estimate the effect sizes of recurrent and nonrecurrent CNVs on IQ. Design, Setting, and Participants: This study identified all CNVs that were 50 kilobases (kb) or larger in 2 general population cohorts (the IMAGEN project and the Saguenay Youth Study) with measures of IQ...
March 21, 2018: JAMA Psychiatry
Noel Lianga, Carole Doré, Erin K Kennedy, Elaine Yeh, Elizabeth C Williams, Camille Marie Fortinez, Alick Wang, Kerry S Bloom, Adam D Rudner
Anaphase onset is an irreversible cell cycle transition that is triggered by the activation of the protease Separase. Separase cleaves the Mcd1 (also known as Scc1) subunit of Cohesin, a complex of proteins that physically links sister chromatids, triggering sister chromatid separation. Separase is regulated by the degradation of the anaphase inhibitor Securin which liberates Separase from inhibitory Securin/Separase complexes. In many organisms, Securin is not essential suggesting that Separase is regulated by additional mechanisms...
March 21, 2018: PLoS Genetics
Gábor Zsurka, Viktoriya Peeva, Alexander Kotlyar, Wolfram S Kunz
Recent deep sequencing data has provided compelling evidence that the spectrum of somatic point mutations in mitochondrial DNA (mtDNA) in aging tissues lacks G > T transversion mutations. This fact cannot, however, be used as an argument for the missing contribution of reactive oxygen species (ROS) to mitochondria-related aging because it is probably caused by the nucleotide selectivity of mitochondrial DNA polymerase γ (POLG). In contrast to point mutations, the age-dependent accumulation of mitochondrial DNA deletions is, in light of recent experimental data, still explainable by the segregation of mutant molecules generated by the direct mutagenic effects of ROS (in particular, of HO· radicals formed from H₂O₂ by a Fenton reaction)...
March 21, 2018: Genes
Despina Apostolopoulou, Olga S Kaxira, Angeliki Hatzaki, Kanaris P Panagopoulos, Konstantinos Alexandrou, Alexander Stratoudakis, Panagoula Kollia, Vassiliki Aleporou
INTRODUCTION: Craniosynostosis, the premature fusion of cranial sutures, is usually divided into 2 major categories: syndromic and nonsyndromic. Mutations in the FGFR1, FGFR2, FGFR3, TWIST1, and EFNB1 genes cause the common craniosynostosis syndromes Muenke, Crouzon and Crouzon with acanthosis nigricans, Apert, Pfeiffer, Saethre-Chotzen, and Craniofrontonasal. Overlapping features among craniosynostosis syndromes, phenotypic heterogeneity even within the same syndrome, especially in the case of Muenke syndrome, and inadequate clinical evaluation can lead to misdiagnosis, which molecular testing can help clarify...
January 1, 2018: Cleft Palate-craniofacial Journal
Dong-Min Kim, Dong Ho Kim, Woong Jung, Kye Young Lee, Dong-Eun Kim
Mutations in epidermal growth factor receptor (EGFR) are known as biomarkers that cause non-small cell lung cancer. Particularly, approximately 45% of non-small cell lung cancer patients possess a deletion in exon 19 of the EGFR gene. A less invasive method for detecting the EGFR mutation is required; thus, we developed a simple polymerase chain reaction (PCR)-based method for detecting EGFR exon 19 deletion by using a quencher-free fluorescent probe DNA and graphene oxide (GO). In the presence of the exon 19 deletion mutation, the fluorophore-labeled DNA probe was designed to be fully complementary to the mutant sequences...
March 21, 2018: Analyst
Shenghao Wang, Muhammad Kalim, Keying Liang, Jinbiao Zhan
Glypican-3 (GPC3) is an integral membrane proteoglycan, which contains a core protein anchored to the cytoplasmic membrane through a glycosyl phosphatidylinositol linkage. The glypican-3 can regulate the signaling pathways, thereby enhances cell division, growth, and apoptosis in certain cell types. It is almost non-existent on the surface of the human normal cell membrane and highly expresses on the membrane of hepatocellular carcinoma (HCC) cells. It has been well established that GPC3 provide a useful diagnostic marker...
March 21, 2018: Preparative Biochemistry & Biotechnology
Nicola Montalbetti, James G Rooney, Allison L Marciszyn, Marcelo D Carattino
Acid-sensing ion channels (ASICs) are trimeric proton-activated cation selective neuronal channels that are considered to play important roles in mechanosensation and nociception. Here we investigated the role of ASIC3, a subunit primarily expressed in sensory neurons, in bladder sensory signaling and function. We found that extracellular acidification evokes a transient increase in current, consistent with the kinetics of activation and desensitization of ASICs, in ~ 25% of the bladder sensory neurons harvested from both wild type (WT) and ASIC3 knockout (KO) mice...
March 21, 2018: American Journal of Physiology. Renal Physiology
Vallence Nsabiyera, Harbans S Bariana, Naeela Qureshi, Debbie Wong, Matthew J Hayden, Urmil K Bansal
A new adult plant stripe rust resistance gene, Yr80, was identified in a common wheat landrace Aus27284. Linked markers were developed and validated for their utility in marker-assisted selection. Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is among the most important constraints to global wheat production. The identification and characterisation of new sources of host plant resistance enrich the gene pool and underpin deployment of resistance gene pyramids in new cultivars. Aus27284 exhibited resistance at the adult plant stage against predominant Pst pathotypes and was crossed with a susceptible genotype Avocet S...
March 20, 2018: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
Tenpei Akita, Kazushi Aoto, Mitsuhiro Kato, Masaaki Shiina, Hiroki Mutoh, Mitsuko Nakashima, Ichiro Kuki, Shin Okazaki, Shinichi Magara, Takashi Shiihara, Kenji Yokochi, Kaori Aiba, Jun Tohyama, Chihiro Ohba, Satoko Miyatake, Noriko Miyake, Kazuhiro Ogata, Atsuo Fukuda, Naomichi Matsumoto, Hirotomo Saitsu
Objective: α ( CAMK2A ) and β ( CAMK2B ) isoforms of Calcium/calmodulin-dependent protein kinase II (CaMKII) play a pivotal role in neuronal plasticity and in learning and memory processes in the brain. Here, we explore the possible involvement of α - and β -CaMKII variants in neurodevelopmental disorders. Methods: Whole-exome sequencing was performed for 976 individuals with intellectual disability, developmental delay, and epilepsy. The effect of CAMK2A and CAMK2B variants on CaMKII structure and firing of neurons was evaluated by computational structural analysis, immunoblotting, and electrophysiological analysis...
March 2018: Annals of Clinical and Translational Neurology
Keshav Gopal, Malak Almutairi, Rami Al Batran, Farah Eaton, Manoj Gandhi, John Reyes Ussher
Obesity and type 2 diabetes (T2D) increase the risk for cardiomyopathy, which is the presence of ventricular dysfunction in the absence of underlying coronary artery disease and/or hypertension. As myocardial energy metabolism is altered during obesity/T2D (increased fatty acid oxidation and decreased glucose oxidation), we hypothesized that restricting myocardial glucose oxidation in lean mice devoid of the perturbed metabolic milieu observed in obesity/T2D would produce a cardiomyopathy phenotype, characterized via diastolic dysfunction...
2018: Frontiers in Cardiovascular Medicine
Paul P Jung, Zhi Zhang, Nicole Paczia, Christian Jaeger, Tomasz Ignac, Patrick May, Carole L Linster
Aging is a complex trait of broad scientific interest, especially because of its intrinsic link with common human diseases. Pioneering work on aging-related mechanisms has been made in Saccharomyces cerevisiae , mainly through the use of deletion collections isogenic to the S288c reference strain. In this study, using a recently published high-throughput approach, we quantified chronological life span (CLS) within a collection of 58 natural strains across seven different conditions. We observed a broad aging variability suggesting the implication of diverse genetic and environmental factors in chronological aging control...
2018: NPJ Aging and Mechanisms of Disease
Mohammad Safarian, Ali Taghipour, Abdolreza Norouzy, Mostafa Mozhdehifard, Mahdieh Pouryazdanpanah
Background: Recently, nutrition support was implemented as a part of clinical services in hospitals. The implementation of nutrition support needs to be assessed for its improvement. Objective: This study aimed to develop and validate a questionnaire to assess the state of nutrition support in Iranian hospitals. Methods: A mixed method approach was used in this study. This study was performed in training hospitals of Iran in 2016. In the development stage, pre-determined keywords were searched on international electronic databases...
December 2017: Electronic Physician
David M Barris, Shoshana B Weiner, Robert A Dubin, Michael Fremed, Xusheng Zhang, Sajida Piperdi, Wendong Zhang, Shahina Maqbool, Jonathan Gill, Michael Roth, Bang Hoang, David Geller, Richard Gorlick, Daniel A Weiser
Identification and quantification of somatic alterations in plasma-derived, circulating tumor DNA (ctDNA) is gaining traction as a non-invasive and cost effective method of disease monitoring in cancer patients, particularly to evaluate response to treatment and monitor for disease recurrence. To our knowledge, genetic analysis of ctDNA in osteosarcoma has not yet been studied. To determine whether somatic alterations can be detected in ctDNA and perhaps applied to patient management in this disease, we collected germline, tumor, and serial plasma samples from pediatric, adolescent, and young adult patients with osteosarcoma and used targeted Next Generation Sequencing (NGS) to identify somatic single nucleotide variants (SNV), insertions and deletions (INDELS), and structural variants (SV) in 7 genes commonly mutated in osteosarcoma...
February 27, 2018: Oncotarget
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"