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https://www.readbyqxmd.com/read/27913592/complexin-mutants-reveal-partial-segregation-between-recycling-pathways-that-drive-evoked-and-spontaneous-neurotransmission
#1
Nadezhda Sabeva, Richard W Cho, Alexander Vasin, Agustin Gonzalez, J Troy Littleton, Maria Bykhovskaia
: Synaptic vesicles fuse at morphological specializations in the presynaptic terminal termed active zones (AZs). Vesicle fusion can occur spontaneously or in response to an action potential. Following fusion, vesicles are retrieved and recycled within nerve terminals. It is still unclear whether vesicles that fuse spontaneously or following evoked release share similar recycling mechanisms. Genetic deletion of the SNARE-binding protein complexin dramatically increases spontaneous fusion, with the protein serving as the synaptic vesicle fusion clamp at Drosophila synapses...
December 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27913361/constrained-null-space-component-analysis-for-semiblind-source-separation-problem
#2
Wen-Liang Hwang, Keng-Shih Lu, Jinn Ho
The blind source separation (BSS) problem extracts unknown sources from observations of their unknown mixtures. A current trend in BSS is the semiblind approach, which incorporates prior information on sources or how the sources are mixed. The constrained independent component analysis (ICA) approach has been studied to impose constraints on the famous ICA framework. We introduced an alternative approach based on the null space component (NCA) framework and referred to the approach as the c-NCA approach. We also presented the c-NCA algorithm that uses signal-dependent semidefinite operators, which is a bilinear mapping, as signatures for operator design in the c-NCA approach...
November 29, 2016: IEEE Transactions on Neural Networks and Learning Systems
https://www.readbyqxmd.com/read/27912196/nox-isoforms-in-the-development-of-abdominal-aortic-aneurysm
#3
Kin Lung Siu, Qiang Li, Yixuan Zhang, Jun Guo, Ji Youn Youn, Jie Du, Hua Cai
Oxidative stress plays an important role in the formation of abdominal aortic aneurysm (AAA), and we have recently established a causal role of uncoupled eNOS in this severe human disease. We have also shown that activation of NADPH oxidase (NOX) lies upstream of uncoupled eNOS. Therefore, identification of the specific NOX isoforms that are required for eNOS uncoupling and AAA formation would ultimately lead to novel therapies for AAA. In the present study, we used the Ang II infused hph-1 mice to examine the roles of NOX isoforms in the development of AAA...
November 19, 2016: Redox Biology
https://www.readbyqxmd.com/read/27912060/the-hippo-pathway-kinases-lats1-2-suppress-cancer-immunity
#4
Toshiro Moroishi, Tomoko Hayashi, Wei-Wei Pan, Yu Fujita, Matthew V Holt, Jun Qin, Dennis A Carson, Kun-Liang Guan
Poorly immunogenic tumor cells evade host immunity and grow even in the presence of an intact immune system, but the complex mechanisms regulating tumor immunogenicity have not been elucidated. Here, we discovered an unexpected role of the Hippo pathway in suppressing anti-tumor immunity. We demonstrate that, in three different murine syngeneic tumor models (B16, SCC7, and 4T1), loss of the Hippo pathway kinases LATS1/2 (large tumor suppressor 1 and 2) in tumor cells inhibits tumor growth. Tumor regression by LATS1/2 deletion requires adaptive immune responses, and LATS1/2 deficiency enhances tumor vaccine efficacy...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27912022/inferring-species-interactions-from-co-occurrence-data-with-markov-networks
#5
David J Harris
Inferring species interactions from co-occurrence data is one of the most controversial tasks in community ecology. One difficulty is that a single pairwise interaction can ripple through an ecological network and produce surprising indirect consequences. For example, the negative correlation between two competing species can be reversed in the presence of a third species that outcompetes both of them. Here, I apply models from statistical physics, called Markov networks or Markov random fields, that can predict the direct and indirect consequences of any possible species interaction matrix...
December 2016: Ecology
https://www.readbyqxmd.com/read/27911940/isoform-specific-effects-of-wild-type-ras-genes-on-carcinogen-induced-lung-tumorigenesis-in-mice
#6
Jamie D Weyandt, John M Carney, Elizabeth N Pavlisko, MengMeng Xu, Christopher M Counter
The gene KRAS is commonly mutated in lung cancer to encode a constitutively active and oncogenic protein that is well established to initiate and maintain lung tumorigenesis. However, the remaining wild-type KRAS protein, or the other family members HRAS and NRAS, can still be activated in the presence of oncogenic KRAS. Moreover, loss of any one of these three genes has been shown to increase the sensitivity of mice to the carcinogen urethane, which induces Kras mutation-positive early lung lesions. To determine the contribution of progressively disrupting Hras and Nras genes on urethane lung tumorigenesis, mice with different combinations of wild-type and null alleles of Hras and Nras were exposed with urethane and tumor burden was assessed...
2016: PloS One
https://www.readbyqxmd.com/read/27911860/id4-regulates-transcriptional-activity-of-wild-type-and-mutant-p53-via-k373-acetylation
#7
Derrick J Morton, Divya Patel, Jugal Joshi, Aisha Hunt, Ashley E Knowell, Jaideep Chaudhary
Given that mutated p53 (50% of all human cancers) is over-expressed in many cancers, restoration of mutant p53 to its wild type biological function has been sought after as cancer therapy. The conformational flexibility has allowed to restore the normal biological function of mutant p53 by short peptides and small molecule compounds. Recently, studies have focused on physiological mechanisms such as acetylation of lysine residues to rescue the wild type activity of mutant p53. Using p53 null prostate cancer cell line we show that ID4 dependent acetylation promotes mutant p53 DNA-binding capabilities to its wild type consensus sequence, thus regulating p53-dependent target genes leading to subsequent cell cycle arrest and apoptosis...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911821/myth4-ferm-myosins-have-an-ancient-and-conserved-role-in-filopod-formation
#8
Karl J Petersen, Holly V Goodson, Ashley L Arthur, G W Gant Luxton, Anne Houdusse, Margaret A Titus
The formation of filopodia in Metazoa and Amoebozoa requires the activity of myosin 10 (Myo10) in mammalian cells and of Dictyostelium unconventional myosin 7 (DdMyo7) in the social amoeba Dictyostelium However, the exact roles of these MyTH4-FERM myosins (myosin tail homology 4-band 4.1, ezrin, radixin, moesin; MF) in the initiation and elongation of filopodia are not well defined and may reflect conserved functions among phylogenetically diverse MF myosins. Phylogenetic analysis of MF myosin domains suggests that a single ancestral MF myosin existed with a structure similar to DdMyo7, which has two MF domains, and that subsequent duplications in the metazoan lineage produced its functional homolog Myo10...
November 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911277/gstm1-and-gstt1-polymorphisms-are-associated-with-increased-bladder-cancer-risk-evidence-from-updated-meta-analysis
#9
Cui Yu, Chen Hequn, Liu Longfei, Wang Long, Chen Zhi, Zeng Feng, Chen Jinbo, Li Chao, Zu Xiongbing
BACKGROUND: Previous studies have indicated association between GSTM1 and GSTT1 gene polymorphisms and bladder cancer susceptibility, but the results have been inconclusive. Here, we performed a meta-analysis to investigate the association between GSTM1/GSTT1 deletion polymorphisms and bladder cancer susceptibility. METHODS: We searched for all studies investigating the association between GSTM1 or GSTT1 polymorphism and bladder cancer susceptibility in Pubmed, Web of Knowledge, and the Cochrane Central Search Library...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27910472/hanle-effect-as-a-magnetic-diagnostic-for-field-reversed-configuration-plasmas
#10
Deepak K Gupta
Hanle effect is presented as a low magnetic-field diagnostic for field-reversed configuration (FRC) plasmas. The non-perturbative technique is capable of measuring not only magnetic-field profile and direction but also field-null position and its shape. Conditions and configurations for the measurement are discussed. The technique is applicable to other low magnetic-field laboratory plasmas, e.g., magnetic-cusps, where measurements of low field are desirable, and it may also be extended to measure the two-dimensional vector magnetic-field...
November 2016: Review of Scientific Instruments
https://www.readbyqxmd.com/read/27909264/global-ablation-of-the-mitochondrial-calcium-uniporter-increases-glycolysis-in-cortical-neurons-subjected-to-energetic-stressors
#11
Matthew Nichols, Pia A Elustondo, Jordan Warford, Aruloli Thirumaran, Evgeny V Pavlov, George S Robertson
The effects of global mitochondrial calcium (Ca(2+)) uniporter (MCU) deficiency on hypoxic-ischemic (HI) brain injury, neuronal Ca(2+) handling, bioenergetics and hypoxic preconditioning (HPC) were examined. Forebrain mitochondria isolated from global MCU nulls displayed markedly reduced Ca(2+) uptake and Ca(2+)-induced opening of the membrane permeability transition pore. Despite evidence that these effects should be neuroprotective, global MCU nulls and wild-type (WT) mice suffered comparable HI brain damage...
December 1, 2016: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/27908841/study-of-gene-polymorphisms-of-glutathione-s-transferase-t1-m1-in-egyptian-children-and-adolescents-with-type-1-diabetes-mellitus
#12
Naglaa Barseem, Mona Elsamalehy
OBJECTIVE: To evaluate the association of glutathione S- transferase mu 1 (GST M1) and glutathione S- transferase theta 1 (GST T1) polymorphisms with the development of T1DM and disease-related risk factors. METHODS: Sixty-four diabetic children and 41 controls were enrolled and subjected to fasting glucose, serum creatinine, lipid profile, HbA1c and evaluation of GST T1 and M1 genetic polymorphisms using polymerase chain reaction (PCR). RESULTS: There were significantly higher fasting glucose, glycosylated hemoglobin (HbA1c) and cholesterol in the diabetics...
December 2, 2016: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/27908662/too-cool-symbolic-but-not-iconic-stimuli-impair-4-year-old-children-s-performance-on-the-delay-of-gratification-choice-paradigm
#13
Lisa G Labuschagne, Taylor-Jane Cox, Kaitlyn Brown, Damian Scarf
A common method of improving the performance of children and non-human primates on the delay-of-gratification maintenance paradigm and measures of executive function (e.g., the Less is More task) is to represent the rewards subjects can acquire symbolically. This method, known as symbolic distancing, is thought to lower activation of the "hot" impulsive system and allow the "cool" rational system to dominate processing. Surprisingly, in contrast to its impact on the measures noted above, recent developmental and comparative studies have reported that symbolic distancing has a null or negative impact on performance on the delay-of-gratification choice paradigm...
November 28, 2016: Behavioural Processes
https://www.readbyqxmd.com/read/27908661/uniform-low-level-dystrophin-expression-in-the-heart-partially-preserved-cardiac-function-in-an-aged-mouse-model-of-duchenne-cardiomyopathy
#14
Nalinda B Wasala, Yongping Yue, Jenna Vance, Dongsheng Duan
Dystrophin deficiency results in Duchenne cardiomyopathy, a primary cause of death in Duchenne muscular dystrophy (DMD). Gene therapy has shown great promise in ameliorating the cardiac phenotype in mouse models of DMD. However, it is not completely clear how much dystrophin is required to treat dystrophic heart disease. We and others have shown that mosaic dystrophin expression at the wild-type level, depending on the percentage of dystrophin positive cardiomyocytes, can either delay the onset of or fully prevent cardiomyopathy in dystrophin-null mdx mice...
November 28, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27908293/autosomal-genetic-control-of-human-gene-expression-does-not-differ-across-the-sexes
#15
Irfahan Kassam, Luke Lloyd-Jones, Alexander Holloway, Kerrin S Small, Biao Zeng, Andrew Bakshi, Andres Metspalu, Greg Gibson, Tim D Spector, Tonu Esko, Grant W Montgomery, Joseph E Powell, Jian Yang, Peter M Visscher, Allan F McRae
BACKGROUND: Despite their nearly identical genomes, males and females differ in risk, incidence, prevalence, severity and age-at-onset of many diseases. Sexual dimorphism is also seen in human autosomal gene expression, and has largely been explored by examining the contribution of genotype-by-sex interactions to variation in gene expression. RESULTS: In this study, we use data from a mixture of pedigree and unrelated individuals with verified European ancestry to investigate the sex-specific genetic architecture of gene expression measured in whole blood across n=1048 males and n=1005 females by treating gene expression intensities in the sexes as two distinct traits and estimating the genetic correlation (r G) between them...
December 1, 2016: Genome Biology
https://www.readbyqxmd.com/read/27907259/spectral-diversity-area-relationships-for-assessing-biodiversity-in-a%C3%A2-wildland-agriculture-matrix
#16
Kyla Marie Dahlin
Species-area relationships have long been used to assess patterns of species diversity across scales. Here, this concept is extended to spectral diversity using hyperspectral data collected by NASA's Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) over western Michigan. This mixture of mesic forest and agricultural lands offers two end-points on the local-scale diversity continuum; one set of well-mixed forest patches and one set of highly homogeneous agricultural patches. Using the sum of the first three principal component values and the principal components' convex hull volume, spectral diversity was compared within and among these plots and to null expectations for perfectly random and perfectly patchy landscapes...
December 2016: Ecological Applications: a Publication of the Ecological Society of America
https://www.readbyqxmd.com/read/27907250/the-transcriptional-co-activator-bob1-is-associated-with-pathologic-b-cell-responses-in-autoimmune-tissue-inflammation
#17
Maria J Levels, Melissa N Van Tok, Tineke Cantaert, Juan D Cañete, Frans G M Kroese, Kristine Germar, Hergen Spits, Dominique L P Baeten, Nataliya G Yeremenko
OBJECTIVE: The molecular mechanisms steering abnormal B cell responses in autoimmune diseases remain poorly understood. In this study we aimed to identify molecular switches controlling pathological B cell responses in rheumatoid arthritis (RA). METHODS: Candidate molecules were identified by gene expression profiling of RA synovitis and validated by qPCR and immunohistochemistry. B cell-specific expression was confirmed by immunofluorescence, immunoblotting and flow cytometry...
December 1, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/27907172/neuroendocrine-inflammatory-responses-in-overweight-obese-infants
#18
Ana Cristina Resende Camargos, Vanessa Amaral Mendonça, Camila Alves de Andrade, Katherine Simone Caires Oliveira, Rosalina Tossige-Gomes, Etel Rocha-Vieira, Camila Danielle Cunha Neves, Érica Leandro Marciano Vieira, Hércules Ribeiro Leite, Murilo Xavier Oliveira, Antônio Lúcio Teixeira Júnior, Cândido Celso Coimbra, Ana Cristina Rodrigues Lacerda
Childhood obesity is related to a cascade of neuroendocrine inflammatory changes. However, there remains a gap in the current literature regarding the possible occurrence of these changes in overweight/obese infants. The objective of this study was to evaluate adipokines, cortisol, brain-derived neurotrophic factor (BDNF) and redox status in overweight/obese infants versus normal-weight peers. A cross-sectional study was conducted with 50 infants (25 in the overweight/obese group and 25 in the normal-weight group) between 6 and 24 months...
2016: PloS One
https://www.readbyqxmd.com/read/27907129/meningococcal-carriage-in-military-recruits-and-university-students-during-the-pre-menb-vaccination-era-in-greece-2014-2015
#19
Kyriaki Tryfinopoulou, Konstantinos Kesanopoulos, Athanasia Xirogianni, Nektarios Marmaras, Anastasia Papandreou, Vassiliki Papaevangelou, Maria Tsolia, Aftab Jasir, Georgina Tzanakaki
PURPOSE: The aim of the study was to estimate the meningococcal carriage rate and to identify the genotypic characteristics of the strains isolated from healthy military recruits and university students in order to provide data that might increase our understanding on the epidemiology of meningococcus and obtain information which helps to evaluate the potential effects on control programs such as vaccination. METHODS: A total of 1420 oropharyngeal single swab samples were collected from military recruits and university students on voluntary basis, aged 18-26 years...
2016: PloS One
https://www.readbyqxmd.com/read/27907056/understanding-variation-in-sets-of-n-of-1-trials
#20
Artur Araujo, Steven Julious, Stephen Senn
A recent paper in this journal by Chen and Chen has used computer simulations to examine a number of approaches to analysing sets of n-of-1 trials. We have examined such designs using a more theoretical approach based on considering the purpose of analysis and the structure as regards randomisation that the design uses. We show that different purposes require different analyses and that these in turn may produce quite different results. Our approach to incorporating the randomisation employed when the purpose is to test a null hypothesis of strict equality of the treatment makes use of Nelder's theory of general balance...
2016: PloS One
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