323,192 results match your criteria wild type

Computational analysis of deleterious single nucleotide polymorphisms in catechol O-Methyltransferase conferring risk to post-traumatic stress disorder.

J Psychiatr Res 2021 Mar 31;138:207-218. Epub 2021 Mar 31.

Dept. of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, 29208, USA.

Post-traumatic stress disorder (PTSD) is one of the prevalent neurological disorder which is drawing increased attention over the past few decades. Major risk factors for PTSD can be categorized into environmental and genetic factors. Among the genetic risk factors, polymorphisms in the catechol-O-methyltransferase (COMT) gene is known to be associated with the risk for PTSD. Read More

View Article and Full-Text PDF

Complex renal cysts combined with hemorrhage during crizotinib treatment for ALK-rearranged lung adenocarcinoma.

Cancer Treat Res Commun 2021 Apr 9;27:100373. Epub 2021 Apr 9.

Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Xuhui District, West Huaihai Road No. 241, Shanghai, China. Electronic address:

The oral small-molecule tyrosine kinase inhibitor (TKI), crizotinib has been approved as a first-generation anaplastic lymphoma kinase (ALK) inhibitor in treatment of advanced ALK-positive non-small cell lung cancer (NSCLC). Recently, development of complex renal cysts has been reported with crizotinib usage, highlighting the importance of accurate differentiation between complex renal cysts and new metastasis in NSCLC. Here we describe a case study with confirmed EGFR wild-type and ALK-rearranged lung adenocarcinoma who developed complex renal cysts combined with hemorrhage during crizotinib treatment, with no abnormal clinical symptoms or kidney functions observed. Read More

View Article and Full-Text PDF

Overexpression of rice OsWNK9 promotes arsenite tolerance in transgenic Arabidopsis plants.

J Biotechnol 2021 Apr 14. Epub 2021 Apr 14.

Nuclear Agriculture and Biotechnology Division, Bhabha Atomic Research Centre, Mumbai, 400084, India. Electronic address:

Protein kinases are involved in the transfer of phosphate group to serine, threonine, and tyrosine residues of a target protein. 'With No Lysine kinase' (WNK) is a member of the serine/threonine protein kinase family, which has conserved catalytic lysine (K) residue in subdomain I instead of being in subdomain II.The WNKs family members in plants are stress inducible and have been validated for their role in abiotic stress tolerance. Read More

View Article and Full-Text PDF

The effect of mitochondrial calcium uniporter and cyclophilin D knockout on resistance of brain mitochondria to Ca-induced damage.

J Biol Chem 2021 Apr 14:100669. Epub 2021 Apr 14.

Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN. Electronic address:

The mitochondrial calcium uniporter (MCU) and cyclophilin D (CyD) are key players in induction of the permeability transition pore (PTP), which leads to mitochondrial depolarization and swelling, the major sings of Ca-induced mitochondrial damage. Mitochondrial depolarization inhibits ATP production, whereas swelling results in the release of mitochondrial pro-apoptotic proteins. The extent to which simultaneous deletion of MCU and CyD inhibits PTP induction and prevents damage of brain mitochondria is not clear. Read More

View Article and Full-Text PDF

Pr-favoured variants of the bacteriophytochrome from the plant pathogen Xanthomonas campestris hint on light regulation of virulence-associated mechanisms.

FEBS J 2021 Apr 17. Epub 2021 Apr 17.

Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, (C1405BWE) Ciudad Autónoma de Buenos Aires.

Red/far-red light-sensing bacteriophytochrome photoreceptor (BphP) pathways play key roles in bacterial physiology and ecology. These bilin-binding proteins photoswitch between two states, Pr (red absorbing) and Pfr (far-red absorbing). The isomerization of the chromophore and the downstream structural changes result in the light signal transduction. Read More

View Article and Full-Text PDF

LEP (-2548G>A LEP) and LEPR (223Gln>Arg, 109Lys>Arg) polymorphisms as breast cancer risk factors in the Polish female population.

Mol Biol Rep 2021 Apr 17. Epub 2021 Apr 17.

Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 49 Przybyszewskiego St., 60-355, Poznan, Poland.

On a global scale, breast cancer is the most common type of cancer in women, and it is still a growing problem. Therefore, new prognostic or diagnostic markers are required that would facilitate the assessment of patients or provide more efficient therapy, respectively. In these studies, we analyzed the contribution of LEP (2548G>A) and LEPR (109 Lys>Arg and 223Gln>Arg) genes polymorphisms to the risk of breast cancer development. Read More

View Article and Full-Text PDF

Functional rice with tandemly repeated Cbl-b ubiquitin ligase inhibitory pentapeptide prevents denervation-induced muscle atrophy in vivo.

Biosci Biotechnol Biochem 2021 Apr 17. Epub 2021 Apr 17.

Faculty of Life and Environmental Science, Shimane University, Matsue, Shimane 690-8504, Japan.

Ubiquitin ligase Cbl-b play a critical role in non-loading-mediated skeletal muscle atrophy: Cbl-b ubiquitinates insulin receptor substrate-1 (IRS-1), an important insulin-like growth factor-1 signaling intermediate molecule, leading to its degradation and a resulting loss in muscle mass. We reported that intramuscular injection of a pentapeptide, DGpYMP, which acts as a mimic of the phosphorylation site in IRS-1, significantly inhibited denervation-induced skeletal muscle loss. In order to explore the possibility of the prevention of muscle atrophy by diet therapy, we examined the effects of oral administration of transgenic rice containing Cblin (Cbl-b inhibitor) peptide (DGYMP) on denervation-induced muscle mass loss in frogs. Read More

View Article and Full-Text PDF

The Tonoplast-Localized Transporter OsNRAMP2 is involved in Fe Homeostasis and affects Seed Germination in rice.

J Exp Bot 2021 Apr 17. Epub 2021 Apr 17.

Department of Biochemistry & Molecular Biology, College of Life Science, Nanjing Agriculture University, Nanjing, Jiangsu, China.

Vacuolar storage of iron (Fe) is important for Fe homeostasis in plants. When sufficient, the excess Fe could be stored in vacuoles for remobilization in case of Fe deficiency. Although the mechanism of Fe remobilization from vacuoles is critical for crop development under low Fe stress, the transporters that mediate vacuolar Fe translocation into the cytosol in rice remains unknown. Read More

View Article and Full-Text PDF

Dietary-challenged mice with Alzheimer-like pathology show increased energy expenditure and reduced adipocyte hypertrophy and steatosis.

Aging (Albany NY) 2021 Apr 16;13. Epub 2021 Apr 16.

Department of Endocrinology and Metabolism, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin 10117, Germany.

Alzheimer's disease (AD) is frequently accompanied by progressing weight loss, correlating with mortality. Counter-intuitively, weight loss in old age might predict AD onset but obesity in midlife increases AD risk. Furthermore, AD is associated with diabetes-like alterations in glucose metabolism. Read More

View Article and Full-Text PDF

Neuronally expressed a-series gangliosides are sufficient to prevent the lethal age-dependent phenotype in GM3-only expressing mice.

J Neurochem 2021 Apr 17. Epub 2021 Apr 17.

University of Glasgow, Institute of Infection, Immunity & Inflammation.

Gangliosides are expressed on plasma membranes throughout the body and enriched in the nervous system. A critical role for complex a- and b-series gangliosides in central and peripheral nervous system ageing has been established through transgenic manipulation of enzymes in ganglioside biosynthesis. Disrupting GalNAc-transferase (GalNAc-T), thus eliminating all a- and b-series complex gangliosides (with consequent over-expression of GM3 and GD3) leads to an age-dependent neurodegeneration. Read More

View Article and Full-Text PDF


Br J Pharmacol 2021 Apr 17. Epub 2021 Apr 17.

Cyclerion Therapeutics Inc., 301 Binney Street, Cambridge, MA, 02142, USA.

Background And Purpose: Reduced nitric oxide (NO) bioavailability, a hallmark of sickle cell disease (SCD), contributes to intravascular inflammation, vasoconstriction, vaso-occlusion, and organ damage observed in SCD patients. Soluble guanylyl cyclase (sGC) catalyzes synthesis of cyclic guanosine monophosphate (cGMP) in response to NO. cGMP amplifying agents, including NO donors and phosphodiesterase 9 inhibitors, alleviate tumor necrosis factor alpha (TNFα)-induced inflammation in wild-type C57BL/6 mice and in "humanized" mouse models of SCD. Read More

View Article and Full-Text PDF

DNA repair in primordial follicle oocytes following cisplatin treatment.

J Assist Reprod Genet 2021 Apr 16. Epub 2021 Apr 16.

Ovarian Biology Laboratory, Monash Biomedicine Discovery Institute, Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, 3800, Australia.

Purpose: Genotoxic chemotherapy and radiotherapy can cause DNA double stranded breaks (DSBs) in primordial follicle (PMF) oocytes, which then undergo apoptosis. The development of effective new fertility preservation agents has been hampered, in part, by a limited understanding of DNA repair in PMF oocytes. This study investigated the induction of classical DSB repair pathways in the follicles of wild type (WT) and apoptosis-deficient Puma mice in response to DSBs caused by the chemotherapy agent cisplatin. Read More

View Article and Full-Text PDF

Deficiency of optineurin enhances osteoclast differentiation by attenuating the NRF2-mediated antioxidant response.

Exp Mol Med 2021 Apr 16. Epub 2021 Apr 16.

Division of Orthodontics, The Ohio State University College of Dentistry, Columbus, OH, 43210, USA.

Abnormally increased resorption contributes to bone degenerative diseases such as Paget's disease of bone (PDB) through unclear mechanisms. Recently, the optineurin (OPTN) gene has been implicated in PDB, and global OPTN knockout mice (Optn) were shown to exhibit increased formation of osteoclasts (osteoclastogenesis). Growing evidence, including our own, has demonstrated that intracellular reactive oxygen species (ROS) stimulated by receptor activator of nuclear factor kappa-B ligand (RANKL) can act as signaling molecules to promote osteoclastogenesis. Read More

View Article and Full-Text PDF

Multi-omic analyses in Abyssinian cats with primary renal amyloid deposits.

Sci Rep 2021 Apr 16;11(1):8339. Epub 2021 Apr 16.

Department of Veterinary Medicine, University of Milan, 26900, Lodi, Italy.

The amyloidoses constitute a group of diseases occurring in humans and animals that are characterized by abnormal deposits of aggregated proteins in organs, affecting their structure and function. In the Abyssinian cat breed, a familial form of renal amyloidosis has been described. In this study, multi-omics analyses were applied and integrated to explore some aspects of the unknown pathogenetic processes in cats. Read More

View Article and Full-Text PDF

TERT promoter hotspot mutations and gene amplification in metaplastic breast cancer.

NPJ Breast Cancer 2021 Apr 16;7(1):43. Epub 2021 Apr 16.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Metaplastic breast cancers (MBCs) are characterized by complex genomes, which seem to vary according to their histologic subtype. TERT promoter hotspot mutations and gene amplification are rare in common forms of breast cancer, but present in a subset of phyllodes tumors. Here, we sought to determine the frequency of genetic alterations affecting TERT in a cohort of 60 MBCs with distinct predominant metaplastic components (squamous, 23%; spindle, 27%; osseous, 8%; chondroid, 42%), and to compare the repertoire of genetic alterations of MBCs according to the presence of TERT promoter hotspot mutations or gene amplification. Read More

View Article and Full-Text PDF

mRNA-based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents.

NPJ Vaccines 2021 Apr 16;6(1):57. Epub 2021 Apr 16.

CureVac AG, Tuebingen, Germany.

mRNA technologies have recently proven clinical efficacy against coronavirus disease 2019 and are among the most promising technologies to address the current pandemic. Here, we show preclinical data for our clinical candidate CVnCoV, a lipid nanoparticle-encapsulated mRNA vaccine that encodes full-length, pre-fusion stabilised severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein. In contrast to previously published approaches, CVnCoV is exclusively composed of naturally occurring nucleotides. Read More

View Article and Full-Text PDF

Defective viral genomes as therapeutic interfering particles against flavivirus infection in mammalian and mosquito hosts.

Nat Commun 2021 Apr 16;12(1):2290. Epub 2021 Apr 16.

Institut Pasteur, Viral Populations and Pathogenesis Unit, Centre National de la Recherche Scientifique UMR 3569, Paris, France.

Arthropod-borne viruses pose a major threat to global public health. Thus, innovative strategies for their control and prevention are urgently needed. Here, we exploit the natural capacity of viruses to generate defective viral genomes (DVGs) to their detriment. Read More

View Article and Full-Text PDF

IL-27/IL-27R Mediates Protective Immunity against Chlamydial Infection by Suppressing Excessive Th17 Responses and Reducing Neutrophil Inflammation.

J Immunol 2021 Apr 16. Epub 2021 Apr 16.

Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, Tianjin, People's Republic of China

IL-27, a heterodimeric cytokine of the IL-12 family, has diverse influences on the development of multiple inflammatory diseases. In this study, we identified the protective role of IL-27/IL-27R in host defense against respiratory infection and further investigated the immunological mechanism. Our results showed that IL-27 was involved in infection and that IL-27R knockout mice (WSX-1 mice) suffered more severe disease, with greater body weight loss, higher chlamydial loads, and more severe inflammatory reactions in the lungs than C57BL/6 wild-type mice. Read More

View Article and Full-Text PDF

A Rare Autosomal Dominant Variant in Regulator of Calcineurin Type 1 () Gene Confers Enhanced Calcineurin Activity and May Cause FSGS.

J Am Soc Nephrol 2021 Apr 16. Epub 2021 Apr 16.

Division of Nephrology, Department of Pediatrics, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina

Background: Podocyte dysfunction is the main pathologic mechanism driving the development of FSGS and other morphologic types of steroid-resistant nephrotic syndrome (SRNS). Despite significant progress, the genetic causes of most cases of SRNS have yet to be identified.

Methods: Whole-genome sequencing was performed on 320 individuals from 201 families with familial and sporadic NS/FSGS with no pathogenic mutations in any known NS/FSGS genes. Read More

View Article and Full-Text PDF

SLFN11 inactivation induces proteotoxic stress and sensitizes cancer cells to ubiquitin activating enzyme inhibitor TAK-243.

Cancer Res 2021 Apr 16. Epub 2021 Apr 16.

Center for Cancer Research, Developmental Therapeutics Branch & Laboratory of Molecular Pharmacology, National Cancer Institute

Schlafen11 (SLFN11) inactivation occurs in approximately 50% of cancer cell lines and in a large fraction of patient tumor samples, which leads to chemoresistance. Therefore, new therapeutic approaches are needed to target SLFN11-deficient cancers. To that effect, we conducted a drug screen with the NCATS mechanistic drug library of 1978 compounds in isogenic SLFN11-knockout (KO) and wild-type (WT) leukemia cell lines. Read More

View Article and Full-Text PDF

Construction of a fimbriae absent by deleting 64 genes and its application for efficient production of poly-3-hydroxybutyrate and L-threonine.

Appl Environ Microbiol 2021 Apr 16. Epub 2021 Apr 16.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu province, China;

contains 12 chaperone-usher operons for biosynthesis and assembly of various fimbriae. In this study, each of the 12 operons was deleted in MG1655, and the resulting 12 deletion mutants all grew better than the wild type, especially in the nutrient-deficient M9 medium. When the plasmid pBHR68 containing the key genes for polyhydroxyalkanoate production was introduced into these 12 mutants, each mutant synthesized more polyhydroxyalkanoate than the wild type control. Read More

View Article and Full-Text PDF

mTOR inhibitor improves autistic-like behaviors related to Tsc2 haploinsufficiency but not following developmental status epilepticus.

J Neurodev Disord 2021 Apr 17;13(1):14. Epub 2021 Apr 17.

Department of Child and Adolescent Psychiatry, University Hospital and Medical Faculty Carl Gustav Carus, Technical University of Dresden, Dresden, Germany.

Background: Tuberous sclerosis complex (TSC), a multi-system genetic disorder often associated with autism spectrum disorder (ASD), is caused by mutations of TSC1 or TSC2, which lead to constitutive overactivation of mammalian target of rapamycin (mTOR). In several Tsc1+/- and Tsc2+/- animal models, cognitive and social behavior deficits were reversed by mTOR inhibitors. However, phase II studies have not shown amelioration of ASD and cognitive deficits in individuals with TSC during mTOR inhibitor therapy. Read More

View Article and Full-Text PDF

Weak mixed phase in the mutator model.

Phys Rev E 2021 Mar;103(3-1):032113

Science, Mathematics and Technology Cluster, Singapore University of Technology and Design, 8 Somapah Road, S487372 Singapore.

We consider the mutator model with unidirected transitions from the wild type to the mutator type, with different fitness functions for the wild types and mutator types. We calculate both the fraction of mutator types in the population and the surpluses, i.e. Read More

View Article and Full-Text PDF

Involvement of salicylic acid in the response to potassium deficiency revealed by metabolomics.

Plant Physiol Biochem 2021 Apr 6;163:201-204. Epub 2021 Apr 6.

Research School of Biology, ANU College of Science, Australian National University, 2601, Canberra, ACT, Australia; Institut de Recherche en Horticulture et Semences, Université d'Angers, INRAe, 42 rue Georges Morel, 49070, Beaucouzé, France. Electronic address:

Potassium (K) deficiency has consequences not only on cellular ion balance and transmembrane potential but also on metabolism. In fact, several enzymes are K-dependent including enzymes in catabolism, causing an alteration in glycolysis and respiration. In addition, K deficiency is associated with the induction of specific pathways and accumulation of metabolic biomarkers, such as putrescine. Read More

View Article and Full-Text PDF

Poly (ADP-ribose) polymerase inhibitors in solid tumours: Systematic review and meta-analysis.

Eur J Cancer 2021 Apr 13;149:134-152. Epub 2021 Apr 13.

Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Breast Cancer Unit, Azienda Socio Sanitaria Territoriale di Cremona, Cremona, Italy.

Background: Poly (ADP-ribose) polymerase-inhibitors (PARPis) showed antitumour activity in BRCA1/2-mutated cancers, with more heterogeneous outcomes in tumours harbouring mutations that impair other genes involved in the DNA homologous recombination repair (HRR) or wild-type (wt).

Methods: We conducted a systematic review and meta-analysis to better assess the role of PARPis in the treatment of metastatic solid tumours, with and without BRCA1/2 mutations. The primary end-point was progression-free survival (PFS). Read More

View Article and Full-Text PDF

LXRβ is involved in the control of platelet production from megakaryocytes.

Blood Cells Mol Dis 2021 Apr 13;89:102568. Epub 2021 Apr 13.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Liver X receptor β (LXRβ), a nuclear receptor involved in important cellular processes such as cholesterol, glucose and fatty acid metabolism, was suggested to be involved in platelet aggregation but its detailed roles are not clear. In the present study, we evaluated the contribution of LXRβ to platelet functions and production. In the systemic collagen-epinephrine thrombosis mouse model, LXRβ-deficient mice showed increased area of blood clots compared with control wide-type littermates. Read More

View Article and Full-Text PDF

Carotenogenesis of Staphylococcus aureus: New insights and impact on membrane biophysical properties.

Biochim Biophys Acta Mol Cell Biol Lipids 2021 Apr 13:158941. Epub 2021 Apr 13.

Laboratory of Advanced Analytical Techniques in Natural Products (LATNAP), Chemistry Department, Universidad de los Andes, Bogotá, D.C., Colombia. Electronic address:

Staphyloxanthin (STX) is a saccharolipid derived from a carotenoid in Staphylococcus aureus involved in oxidative-stress tolerance and antimicrobial peptide resistance. STX influences the biophysical properties of the bacterial membrane and has been associated to the formation of lipid domains in the regulation of methicillin-resistance. In this work, a targeted metabolomics and biophysical characterization study was carried out to investigate the biosynthetic pathways of carotenoids, and their impact on the membrane biophysical properties. Read More

View Article and Full-Text PDF

Vital roles of Pks11, a highly reducing polyketide synthase, in fungal conidiation, antioxidant activity, conidial cell wall integrity, and UV tolerance of Beauveria bassiana.

J Invertebr Pathol 2021 Apr 13:107588. Epub 2021 Apr 13.

College of Food Science, South China Agricultural University, Guangzhou 510642, China; Lingnan Guangdong Laboratory of Modern Agriculture, Guangzhou, 510642, China. Electronic address:

Fungal polyketide synthases play important and differential roles in synthesizing secondary metabolites and regulating several cell events, including asexual development, environmental adaptation, and pathogenicity. This study shows the important functions of a highly reducing polyketide synthase, Pks11, in Beauveria bassiana, a filamentous fungal insect pathogen used worldwide for pest biocontrol. The deletion of pks11 led to severe defects in conidial yields on different media and a decrease of 36. Read More

View Article and Full-Text PDF

Variations in Env at Amino Acids 328 and 330 Affect HIV-1 Replicative Fitness and Entry Inhibitor Sensitivity.

Virus Res 2021 Apr 13:198424. Epub 2021 Apr 13.

Unit of HIV Molecular Epidemiology and Virology, State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430071, China. Electronic address:

While the variations in the HIV-1 Env V3 loop have been the focus of much research to explore its functional effect, how specific mutations of certain amino acids in the V3 loop affect viral fitness remains unclear. In this study, we evaluated a series of natural polymorphisms at positions 328 and 330 with different combinations of adjacent glycosylation sites in the HIV-1 subtype B backbone to address their role in replicative fitness and sensitivity to entry inhibitors based on analysis of env sequence frequency at the population level. Pairwise growth competition experiment showed that wild-type virus with major consensus amino acids obviously had higher replicative fitness (P < 0. Read More

View Article and Full-Text PDF

Lens-specific conditional knockout of tropomyosin 1 gene in mice causes abnormal fiber differentiation and lens opacity.

Mech Ageing Dev 2021 Apr 15;196:111492. Epub 2021 Apr 15.

Department of Ophthalmology, Kanazawa Medical University, Ishikawa, Japan. Electronic address:

Tropomyosin (Tpm) 1 and 2 are important in the epithelial mesenchymal transition of lens epithelial cells; however, the effect of Tpm1 depletion during aging remains obscure. We analyzed the age-related changes in the crystalline lens of Tpm1- conditional knockout mice (Tpm1-CKO). Floxed alleles of Tpm1 were conditionally deleted in the lens, using Pax6-cre transgenic mice. Read More

View Article and Full-Text PDF