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https://www.readbyqxmd.com/read/29161781/in-silico-docking-studies-of-lupeol-with-mapk-pathway-proteins-raf-1-mek-erk
#1
Mital H Bhatt, Chirag K Prajapati, M N Reddy
Lupeol, A triterpenoid found in variety of plants is reported to have beneficial medicinal effects on several ailments. Lupeol is also found to show inhibitory effect on proliferation of breast cancer cells. Metastasis is considered to be a major cause for worldwide deaths related to cancer. Ras related MAPK Signaling Pathway is one of the crucial pathways leading to metastasis. Lupeols binding possibility with Ras is already reported. In present study, Interaction between with downstream proteins of Ras- MAPK pathway, Raf ,MEK ,ERK1/2 and their corresponding domains are studied using STRING Database and their structures are retrieved in PDB Format...
November 2017: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/29161772/microarray-analysis-of-gene-expression-in-the-cyclooxygenase-cox-knockout-mice-a-connection-to-autism-spectrum-disorder
#2
Ravneet Rai-Bhogal, Eizaaz Ahmad, Hongyan Li, Dorota A Crawford
The cellular and molecular events that take place during brain development play an important role in governing function of the mature brain. Lipid signalling molecules such as prostaglandin E2 (PGE2 ) play an important role in healthy brain development. Abnormalities along the COX/PGE2 signalling pathway due to genetic or environmental causes have been linked to Autism Spectrum Disorders (ASDs). This study aims to evaluate the effect of altered COX/PGE2 signalling on development and function of the prenatal brain using male mice lacking cyclooxygenase-1 and -2 (COX-1(-/-) and COX-2(-/-) ) as potential model systems of ASD...
November 21, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29161765/mir-335-inhibited-cell-proliferation-of-lung-cancer-cells-by-target-tra2%C3%AE
#3
Jian Liu, Tingting Bian, Jia Feng, Li Qian, Jianguo Zhang, Daishan Jiang, Qing Zhang, Xiaoli Li, Yifei Liu, Jiahai Shi
Accumulating evidence has suggested that the dysregulation of miRNAs is an important factor in the pathogenesis of lung cancer. Here, we demonstrate that miR-335 expression is reduced in non-small cell lung cancer (NSCLC) tumors relative to non-cancerous adjacent tissues, whilst the expression of Tra2β is increased. In addition, clinical data revealed that the increased Tra2β and decreased miR-335 expression observed in NSCLC cells was associated with poor patient survival rates. In-vitro experimentation showed that the overexpression of miR-335 inhibited the growth, invasion and migration capabilities of A459 lung cancer cells, by targeting Tra2β...
November 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/29161753/improving-the-efficacy-of-proteasome-inhibitors-in-the-treatment-of-renal-cell-carcinoma-by-combination-with-the-hiv-protease-inhibitors-lopinavir-or-nelfinavir
#4
Dominik Abt, Andrej Besse, Lenka Sedlarikova, Marianne Kraus, Juergen Bader, Tobias Silzle, Martina Vodinska, Ondrej Slaby, Hans-Peter Schmid, Daniel Stephan Engeler, Christoph Driessen, Lenka Besse
OBJECTIVES: To assess the potential of second-generation proteasome inhibition by carfilzomib and its combination with the HIV-protease inhibitors (HIV-PIs) lopinavir and nelfinavir in vitro for improved treatment of clear cell renal cell cancer (ccRCC). MATERIALS AND METHODS: Cytotoxicity, reactive oxygen species (ROS) production and unfolded protein response (UPR) activation of proteasome inhibitors, HIV-PIs and their combination was assessed in 3 cell lines and primary cells derived from 3 ccRCC tumors by MTS assay, flow cytometry, quantitative PCR and western blot, respectively...
November 21, 2017: BJU International
https://www.readbyqxmd.com/read/29161706/endotoxin-effects-on-cardiac-and-renal-functions-and-cardiorenal-syndromes
#5
Grazia Maria Virzì, Anna Clementi, Alessandra Brocca, Claudio Ronco
Gram-negative sepsis is a major cause of morbidity and mortality in critical ill patients. Recent findings in molecular biology and in signaling pathways have enhanced our understanding of its pathogenesis and opened up opportunities of innovative therapeutic approaches. Endotoxin plays a pivotal role in the pathogenesis of multi-organ dysfunction in the setting of gram-negative sepsis. Indeed, heart and kidney impairments seem to be induced by the release of circulating pro-inflammatory and pro-apoptotic mediators triggered by endotoxin interaction with immune cells...
November 22, 2017: Blood Purification
https://www.readbyqxmd.com/read/29161701/yin-yang-1-dynamically-regulates-antiviral-innate-immune-responses-during-viral-infection
#6
Jie Zan, Hao Zhang, Ai-Ping Gu, Kai-Lun Zhong, Min-Yi Lu, Xiao-Xin Bai, Jin-Yang Zhang, Jun Cai
BACKGROUND/AIMS: Type I interferon (IFN-1) production and IFN-1 signaling play critical roles in the host antiviral innate immune responses. Although transcription factor Yin Yang 1 (YY1) has been reported to have a dual activator/repressor role during the regulation of interferon beta (IFN-β) promoter activity, the roles of YY1 in the regulation of upstream signaling pathways leading to IFN-1 induction and IFN-1 signaling during viral infection remain to be elucidated. METHODS: The roles of YY1 in IFN-1 production and IFN-1 signaling were investigated using immunoblotting, real-time PCR, small interfering RNA (siRNA)-mediated YY1 knockdown, YY1 overexpression by transient transfection, and co-immunoprecipitation, using mouse cells...
November 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29161694/immunohistochemical-localization-of-darpp-32-in-the-brain-of-two-lungfishes-further-assessment-of-its-relationship-with-the-dopaminergic-system
#7
Jesús M López, Ruth Morona, Agustín González
The distribution of DARPP-32 (a phosphoprotein related to the dopamine D1 receptor) has been widely used as a means to clarify the brain regions with dopaminoceptive cells, primarily in representative species of tetrapods. The relationship between dopaminergic and dopaminoceptive elements is frequently analyzed using the catecholamine marker tyrosine hydroxylase (TH). In the present study, by means of combined immunohistochemistry, we have analyzed these relationships in lungfishes, the only group of sarcopterygian fishes represented by 6 extant species that are the phylogenetically closest living relatives of tetrapods...
November 22, 2017: Brain, Behavior and Evolution
https://www.readbyqxmd.com/read/29161661/chlorogenic-acid-prevents-diabetic-nephropathy-by-inhibiting-oxidative-stress-and-inflammation-through-modulation-of-the-nrf2-ho-1-and-nf-%C3%A4-b-pathways
#8
Liping Bao, Jushuang Li, Dongqing Zha, Lian Zhang, Ping Gao, Tao Yao, Xiaoyan Wu
Oxidative and inflammatory damage have been suggested to play important roles in the pathogenesis of diabetic nephropathy (DN). Chlorogenic acid (CGA) is one of the most abundant polyphenols and has known immunoprotective, antioxidant and anti-inflammatory properties. In the present study, animal experiments were designed to examine the protective effects of CGA in DN, and cellular experiments were designed to explore the underlying mechanisms. CGA significantly attenuated diabetic renal damage based on histological pathology and molecular biological methods...
November 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29161636/infant-hpa-axis-as-a-potential-mechanism-linking-maternal-mental-health-and-infant-telomere-length
#9
Benjamin W Nelson, Nicholas B Allen, Heidemarie Laurent
Maternal depression has been suggested to be an independent risk factor for both dysregulated hypothalamic-pituitary-adrenal axis (HPA) functioning and shorter telomere length in offspring. In contrast, research suggests that individual differences in mindfulness may act as a protective factor against one's own telomere degradation. Currently, research has yet to investigate the association between longitudinal changes in maternal mental health (depressive symptoms and mindfulness) and salivary infant telomere length, and whether such changes might be mediated by alterations in infant cortisol response...
November 18, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29161622/on-denny-brown-s-spastic-dystonia-what-is-it-and-what-causes-it
#10
REVIEW
Jakob Lorentzen, Maud Pradines, Jean-Michel Gracies, Jens Bo Nielsen
In this review, we will work around two simple definitions of two different entities, which most often co-exist in patients with lesions to central motor pathways: Spasticity is "Enhanced excitability of velocity-dependent responses to phasic stretch at rest", which will not be the subject of this review, while Spastic dystonia is tonic, chronic, involuntary muscle contraction in the absence of any stretch or any voluntary command (Gracies, 2005). Spastic dystonia is a much less well understood entity that will be the subject this review...
November 4, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/29161606/maternal-depressive-symptoms-and-adolescent-academic-attainment-testing-pathways-via-parenting-and-self-control
#11
Terry Ng-Knight, Katherine H Shelton, Norah Frederickson, I C McManus, Frances Rice
Maternal depression is associated with reduced academic attainment in children, however, it is not clear how this association comes about. Depressive symptoms are associated with impairment in social roles including parenting. Children's self-control is an important contributor to academic attainment and is influenced by parenting. We therefore hypothesised that impaired parenting and children's self-control may mediate links between maternal depression and children's academic attainment. Data were from a brief longitudinal study (3 waves) of UK children aged 11-12 years and their mothers...
November 18, 2017: Journal of Adolescence
https://www.readbyqxmd.com/read/29161595/a-coincidence-detection-mechanism-controls-px-bar-domain-mediated-endocytic-membrane-remodeling-via-an-allosteric-structural-switch
#12
Wen-Ting Lo, Andreja Vujičić Žagar, Fabian Gerth, Martin Lehmann, Dymtro Puchkov, Oxana Krylova, Christian Freund, Leonardo Scapozza, Oscar Vadas, Volker Haucke
Clathrin-mediated endocytosis occurs by bending and remodeling of the membrane underneath the coat. Bin-amphiphysin-rvs (BAR) domain proteins are crucial for endocytic membrane remodeling, but how their activity is spatiotemporally controlled is largely unknown. We demonstrate that the membrane remodeling activity of sorting nexin 9 (SNX9), a late-acting endocytic PX-BAR domain protein required for constriction of U-shaped endocytic intermediates, is controlled by an allosteric structural switch involving coincident detection of the clathrin adaptor AP2 and phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2) at endocytic sites...
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29161591/cell-invasion-in%C3%A2-vivo-via-rapid-exocytosis-of-a-transient-lysosome-derived-membrane-domain
#13
Kaleb M Naegeli, Eric Hastie, Aastha Garde, Zheng Wang, Daniel P Keeley, Kacy L Gordon, Ariel M Pani, Laura C Kelley, Meghan A Morrissey, Qiuyi Chi, Bob Goldstein, David R Sherwood
Invasive cells use small invadopodia to breach basement membrane (BM), a dense matrix that encases tissues. Following the breach, a large protrusion forms to clear a path for tissue entry by poorly understood mechanisms. Using RNAi screening for defects in Caenorhabditis elegans anchor cell (AC) invasion, we found that UNC-6(netrin)/UNC-40(DCC) signaling at the BM breach site directs exocytosis of lysosomes using the exocyst and SNARE SNAP-29 to form a large protrusion that invades vulval tissue. Live-cell imaging revealed that the protrusion is enriched in the matrix metalloprotease ZMP-1 and transiently expands AC volume by more than 20%, displacing surrounding BM and vulval epithelium...
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29161586/re-cyclin-cell-cycle-components-to-make-nets
#14
Jean Albrengues, Robert W Wysocki, Laura Maiorino, Mikala Egeblad
Neutrophil extracellular traps (NETs) are critical for the clearance of large pathogens and are also implicated in thrombosis, autoimmunity, and cancer. In this issue of Developmental Cell, Amulic et al. (2017) show that the terminally differentiated, non-cycling neutrophils repurpose cell-cycle proteins and pathways to form NETs.
November 20, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29161512/trophodynamics-of-organic-pollutants-in-pelagic-and-benthic-food-webs-of-lake-dianchi-importance-of-ingested-sediment-as-uptake-route
#15
Senrong Fan, Beili Wang, Hang Liu, Shixiong Gao, Tong Li, Shuran Wang, Yong Liu, Xueqin Liu, Yi Wan
Habitat is of great importance in determining the trophic transfer of pollutants in freshwater ecosystems; however, the major factors influencing chemical trophodynamics in pelagic and benthic food webs remain unclear. This study investigated the levels of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), polycyclic aromatic hydrocarbons (PAHs), and substituted PAHs (s-PAHs) in two plankton species, six invertebrate species, and ten fish species collected from Lake Dianchi in southern China. Relatively high concentrations of PAHs and s-PAHs were detected with total concentrations of 11...
November 21, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29161501/phenanthrene-induced-apoptosis-and-its-underlying-mechanism
#16
Xiangsheng Hong, Jianhui Qin, Rui Chen, Lilai Yuan, Jinmiao Zha, Chao Huang, Na Li, Xiaoya Ji, Zijian Wang
Phenanthrene (Phe) is one of the most abundant low-molecular-weight polycyclic aromatic hydrocarbons (PAHs). Widespread human and aquatic organism exposure to Phe has been reported, but the toxic effects of Phe and potential mechanisms are unclear. We focused on the chronic hepatotoxicity of Phe in adult Chinese rare minnows (Gobiocypris rarus) and the underlying mechanisms. The chronic effects of exposing Chinese rare minnows to 8.9, 82.3, or 510.0 μg/L Phe for 30 days were examined by histopathological observation, TUNEL assays, caspase activity assays, and gene expression profiles...
November 21, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29161447/dna-polymerase-beta-participates-in-dna-end-joining
#17
Sreerupa Ray, Gregory Breuer, Michelle DeVeaux, Daniel Zelterman, Ranjit Bindra, Joann B Sweasy
DNA double strand breaks (DSBs) are one of the most deleterious lesions and if left unrepaired, they lead to cell death, genomic instability and carcinogenesis. Cells combat DSBs by two pathways: homologous recombination (HR) and non-homologous end-joining (NHEJ), wherein the two DNA ends are re-joined. Recently a back-up NHEJ pathway has been reported and is referred to as alternative NHEJ (aNHEJ), which joins ends but results in deletions and insertions. NHEJ requires processing enzymes including nucleases and polymerases, although the roles of these enzymes are poorly understood...
November 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29161441/contributions-of-function-altering-variants-in-genes-implicated-in-pubertal-timing-and-body-mass-for-self-limited-delayed-puberty
#18
Sasha R Howard, Leonardo Guasti, Ariel Poliandri, Alessia David, Claudia P Cabrera, Michael R Barnes, Karoliina Wehkalampi, Stephen O'Rahilly, Catherine E Aiken, Anthony P Coll, Marcella Ma, Debra Rimmington, Giles S H Yeo, Leo Dunkel
Context: Self-limited delayed puberty (DP) is often associated with delay in physical maturation, but whilst highly heritable the causal genetic factors remain elusive. Genome-wide association studies of the timing of puberty have identified multiple loci for age of menarche (AAM) in females and voice break in males, particularly in pathways controlling energy balance. Objective/Main outcome measures: We aimed to assess the contribution of rare variants in such genes to the phenotype of familial DP...
November 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29161432/modeling-mutant-wild-type-interactions-to-ascertain-pathogenicity-of-prokr2-missense-variants-in-patients-with-isolated-gnrh-deficiency
#19
Kimberly H Cox, Luciana M B Oliveira, Lacey Plummer, Braden Corbin, Thomas Gardella, Ravikumar Balasubramanian, William F Crowley
A major challenge in human genetics is the validation of pathogenicity of heterozygous missense variants. This problem is well-illustrated by PROKR2 variants associated with Isolated GnRH Deficiency (IGD). Homozygous, loss of function variants in PROKR2 were initially implicated in autosomal recessive IGD; however, most IGD-associated PROKR2 variants are heterozygous. Moreover, while IGD patient cohorts are enriched for PROKR2 missense variants similar rare variants are also found in normal individuals. To elucidate the pathogenic mechanisms distinguishing IGD-associated PROKR2 variants from rare variants in controls, we assessed 59 variants using three approaches: (i) in silico prediction, (ii) traditional in vitro functional assays across 3 signaling pathways with mutant-alone transfections, and (iii) modified in vitro assays with mutant and wild-type expression constructs co-transfected to model in vivo heterozygosity...
November 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29161431/volunteering-in-the-community-potential-benefits-for-cognitive-aging
#20
Hayley Guiney, Liana Machado, Bob G Knight
Objectives: This review aims to advance understanding of the potential benefits of volunteering in the community for older adults' cognitive functioning by taking an in-depth look at the relevant evidence to date. Method: This review describes the main pathways through which volunteering could plausibly benefit cognitive functioning and critically examines research that has specifically investigated links between volunteering and cognition. Fifteen articles that assessed in adults aged ≥ 55 years the relationship between volunteering (predictor) and cognitive functioning (outcome) were identified via literature database searches...
November 17, 2017: Journals of Gerontology. Series B, Psychological Sciences and Social Sciences
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