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Sharon L I Wong, Maria B Sukkar
Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein which regulates interactions between cells and their surrounding extracellular matrix (ECM), and thus governs fundamental cellular functions such as cell adhesion, proliferation and differentiation. SPARC also regulates the expression and activity of numerous growth factors and matrix metalloproteinases essential for ECM degradation and turnover. Studies in SPARC-null mice have revealed a critical role for SPARC in tissue development, injury and repair, and in the regulation of the immune response...
October 19, 2016: British Journal of Pharmacology
Raffaella Sordella, Nitin H Shirole, Debjani Pal, Edward R Kastenhuber, Serif Senturk, Joseph Boroda, Paola Pisterzi, Madison Miller, Gustavo Munoz, Marko Anderluh, Marc Ladanyi, Scott W Lowe
TP53 truncating mutations are common in human tumors and are thought to give rise to p53-null alleles. Here, we show that TP53 exon-6 truncating mutations occur at higher than expected frequencies and produce proteins that lack canonical p53 tumor suppressor activities but promote cancer cell proliferation, survival, and metastasis. Functionally and molecularly, these p53 mutants resemble the naturally occurring alternative p53 splice variant, p53-psi. Accordingly, these mutants can localize to mitochondria where they promote tumor phenotypes by binding and activating the mitochondria inner pore permeability regulator, Cyclophilin D (CypD)...
October 19, 2016: ELife
Karan Kapoor, Michael R Duff, Amit Upadhyay, Joel C Bucci, Arnold M Saxton, Robert J Hinde, Elizabeth E Howell, Jerome Yves Baudry
The dynamics of anion-quadrupole (or anion-) interactions formed between negatively charged (Asp/Glu) and aromatic (Phe) side chains are for the first time computationally characterized in RmlC (PDB: 1EP0), a homodimeric epimerase. Empirical force field-based molecular dynamics simulations predict anion-quadrupole pairs and triplets (anion-anion-anion--) are formed by the protein during the simulated trajectory which suggests that the anion-quadrupole interactions may provide a significant contribution to the overall stability of the protein, with an average of -1...
October 18, 2016: Biochemistry
David R Shanks
Many studies of unconscious processing involve comparing a performance measure (e.g., some assessment of perception or memory) with an awareness measure (such as a verbal report or a forced-choice response) taken either concurrently or separately. Unconscious processing is inferred when above-chance performance is combined with null awareness. Often, however, aggregate awareness is better than chance, and data analysis therefore employs a form of extreme group analysis focusing post hoc on participants, trials, or items where awareness is absent or at chance...
October 17, 2016: Psychonomic Bulletin & Review
A L J J Bronckers, R Jalali, J Lytton
Exposure of forming enamel to fluoride results into formation of hypomineralized enamel. We tested whether enamel hypomineralization was caused by lower expression of the NCKX4/SLC24A4 Ca(2+)-transporter by ameloblasts. Three commercial antibodies against NCKX4 were tested on enamel organs of wild-type and Nckx4-null mice, one of which (a mouse monoclonal) was specific. This antibody gave a prominent staining of the apical plasma membranes of maturation ameloblasts, starting at early maturation. The layer of immuno-positive ameloblasts contained narrow gaps without immunostaining or with reduced staining...
October 17, 2016: Calcified Tissue International
Anita Sadhu, Ryan P Calfee, Andre Guthrie, Lindley B Wall
PURPOSE: To test the null hypothesis that there is no difference in patient-reported and objective outcomes of revision ligament reconstruction and tendon interposition (LRTI) compared with primary LRTI. METHODS: This case-control investigation enrolled 10 patients who had undergone revision LRTI at a tertiary care center. All patients had previously undergone primary trapeziectomy with LRTI. Patients with a minimum of 2 years' follow-up were eligible. All patients completed an in-office study evaluation...
October 14, 2016: Journal of Hand Surgery
Tahnee L Kennedy, Kristy Swiderski, Kate T Murphy, Stefan M Gehrig, Claire L Curl, Chanchal Chandramouli, Mark A Febbraio, Lea M D Delbridge, René Koopman, Gordon S Lynch
Duchenne muscular dystrophy is a severe and progressive striated muscle wasting disorder that leads to premature death from respiratory and/or cardiac failure. We have previously shown that treatment of young dystrophic mdx and dystrophin/utrophin null (dko) mice with BGP-15, a coinducer of heat shock protein 72, ameliorated the dystrophic pathology. We therefore tested the hypothesis that later-stage BGP-15 treatment would similarly benefit older mdx and dko mice when the dystrophic pathology was already well established...
October 14, 2016: American Journal of Pathology
Rowan T Chlebowski, Wendy Barrington, Aaron K Aragaki, JoAnn E Manson, Gloria Sarto, Mary J OʼSullivan, Daniel Wu, Jane A Cauley, Lihong Qi, Robert L Wallace, Ross L Prentice
OBJECTIVE: In postmenopausal black women in the Women's Health Initiative randomized trial, estrogen alone reduced breast cancers but its comprehensive influence on health outcomes in black women is unknown. Therefore, we examined this issue in the Women's Health Initiative overall and by African ancestry. METHODS: A total of 1,616 black women with prior hysterectomy, including 1,061 with percent African ancestry determination, at 40 US centers were randomly assigned to conjugated equine estrogen (0...
October 3, 2016: Menopause: the Journal of the North American Menopause Society
Xiaojuan Huang, Jung-Ho Shin, Azul Pinochet-Barros, Tina T Su, John D Helmann
The Bacillus subtilis MntR metalloregulatory protein senses manganese, an essential element required for central metabolism, oxidative stress resistance and replication. An mntR null mutant is highly sensitive to Mn(II) intoxication, which is attributed in part to the constitutive expression of two importers: the proton-dependent NRAMP family transporter MntH and the ABC transporter MntABCD. Here, we show that an mntR null mutant is still sensitive to Mn(II) intoxication even if both of the import systems are absent...
October 17, 2016: Molecular Microbiology
Hiroki Otsuka, Hideo Sasai, Mina Nakama, Yuka Aoyama, Elsayed Abdelkreem, Hidenori Ohnishi, Vassiliki Konstantopoulou, Jörn Oliver Sass, Toshiyuki Fukao
Beta-ketothiolase deficiency, also known as mitochondrial acetoacetyl-CoA thiolase (T2) deficiency, is an autosomal recessive disease caused by mutations in the acetyl‑CoA acetyltransferase 1 (ACAT1) gene. A German T2‑deficient patient that developed a severe ketoacidotic episode at the age of 11 months, was revealed to be a compound heterozygote of a previously reported null mutation, c.472A>G (p.N158D) and a novel mutation, c.949G>A (p.D317N), in ACAT1. The c.949G>A mutation was suspected to cause aberrant splicing as it is located within an exonic splicing enhancer sequence (c...
October 10, 2016: Molecular Medicine Reports
Osorio Abath Neto, Carlos Otto Heise, Cristiane de Araújo Martins Moreno, Eduardo de Paula Estephan, Lilia Mesrob, Doris Lechner, Anne Boland, Jean-François Deleuze, Acary Souza Bulle Oliveira, Umbertina Conti Reed, Valérie Biancalana, Jocelyn Laporte, Edmar Zanoteli
No abstract text is available yet for this article.
October 17, 2016: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
Kate J Bowen, William S Harris, Penny M Kris-Etherton
Early secondary prevention trials of fish and omega-3 polyunsaturated fatty acid (PUFA) capsules reported beneficial effects on cardiovascular disease (CVD) outcomes, including all-cause mortality and sudden cardiac death. These clinical findings, as well as observational and experimental data, demonstrated that omega-3 PUFAs reduced the risk of coronary outcomes and overall mortality and were the basis for recommendations made in the early 2000s to increase omega-3 PUFA intake. In the last 6 years, however, results from both primary and secondary prevention trials have generally failed to show a beneficial effect of omega-3 PUFA supplementation, bringing current recommendations into question...
November 2016: Current Treatment Options in Cardiovascular Medicine
Zhaojun Cao, Yue Yin, Xuan Sun, Jun Han, Qing Peng Sun, Min Lu, Jinbao Pan, Weixiang Wang
Ash1 is a known H3K36-specific histone demethylase that is required for normal Hox gene expression and fertility in Drosophila and mammals. However, little is known about the expression and function of the fungal ortholog of Ash1 in phytopathogenic fungus Magnaporthe oryzae. Here we report that MoKMT2H, an Ash1-like protein, is required for conidium germination and virulence in rice. We obtained MoKMT2H null mutant (ΔMoKMT2H) using a target gene replacement strategy. In the ΔMoKMT2H null mutants, global histone methyltransferase modifications (H3K4me3, H3K9me3, H3K27me3, and H3K36me2/3) of the genome were unaffected...
2016: BioMed Research International
Jonathan C W Edwards
It is widely perceived that there is a problem in giving a naturalistic account of mental representation that deals adequately with the issue of meaning, interpretation, or significance (semantic content). It is suggested here that this problem may arise partly from the conflation of two vernacular senses of representation: representation-as-origin and representation-as-input. The flash of a neon sign may in one sense represent a popular drink, but to function as a representation it must provide an input to a 'consumer' in the street...
2016: Frontiers in Psychology
Rugmani Padmanabhan Iyer, Lisandra E de Castro Brás, Nicolle L Patterson, Manishabrata Bhowmick, Elizabeth R Flynn, Majdouline Asher, Presley L Cannon, Kristine Y Deleon-Pennell, Gregg B Fields, Merry L Lindsey
Matrix metalloproteinase-9 (MMP-9) is robustly elevated in the first week post-myocardial infarction (MI). Targeted deletion of the MMP-9 gene attenuates cardiac remodeling post-MI by reducing macrophage infiltration and collagen accumulation through increased apoptosis and reduced inflammation. In this study, we used a translational experimental design to determine whether selective MMP-9 inhibition early post-MI would be an effective therapeutic strategy in mice. We enrolled male C57BL/6J mice (3-6months old, n=116) for this study...
October 13, 2016: Journal of Molecular and Cellular Cardiology
Nicolas Rodrigue, Nicolas Lartillot
Codon substitution models have traditionally attempted to uncover signatures of adaptation within protein-coding genes by contrasting the rates of synonymous and nonsynonymous substitutions. Another modeling approach, known as the mutation-selection framework, attempts to explicitly account for selective patterns at the amino acid level, with some approaches allowing for heterogeneity in these patterns across codon sites. Under such a model, substitutions at a given position occur at the neutral or nearly-neutral rate when they are synonymous, or when they correspond to replacements between amino acids of similar fitness; substitutions from high to low (low to high) fitness amino acids have comparatively low (high) rates...
October 15, 2016: Molecular Biology and Evolution
Lauren Alpert Sugden, Sohini Ramachandran
Human population genomic studies have repeatedly observed a decrease in heterozygosity and an increase in linkage disequilibrium with geographic distance from Africa. While multiple demographic models can generate these patterns, many studies invoke the serial founder effect model, in which populations expand from a single origin and each new population's founders represent a subset of genetic variation in the previous population. The model assumes no admixture with archaic hominins, however, recent studies have identified loci in Homo sapiens bearing signatures of archaic introgression...
October 12, 2016: Current Opinion in Genetics & Development
Hongzheng Dai, Victor Wei Zhang, Ayman W El-Hattab, Can Ficicioglu, Marwan Shinawi, Matthew Lines, Andreas Schulze, Markey McNutt, Garret Gotway, Xia Tian, Stella Chen, Jing Wang, William J Craigen, Lee-Jun Wong
Mutations in FBXL4 have recently been recognized to cause a mitochondrial disorder, with clinical features including early-onset lactic acidosis, hypotonia, and developmental delay. FBXL4 sequence analysis was performed in 808 subjects suspected to have a mitochondrial disorder. In addition, 28 samples from patients with early onset of lactic acidosis, but without identifiable mutations in 192 genes known to cause mitochondrial diseases, were examined for FBXL4 mutations. Definitive diagnosis was made in ten new subjects with a total of seven novel deleterious variants; five null and two missense substitutions...
October 15, 2016: Clinical Genetics
Nelly Redolfi, Luisa Galla, Andrea Maset, Luca Murru, Eleonora Savoia, Ilaria Zamparo, Angela Gritti, Pierre Billuart, Maria Passafaro, Claudia Lodovichi
Among the X-linked genes associated to intellectual disability, Oligophrenin-1 (OPHN1) encodes for a Rho GTPase-activating protein, a key regulator of several developmental processes, such as dendrite and spine formation and synaptic activity. Inhibitory interneurons play a key role in the development and function of neuronal circuits. Whether mutation of OPHN1 can affect morphology and synaptic properties of inhibitory interneurons remains poorly understood. To address these open questions, we studied in a well established mouse model of X-linked intellectual disability, i...
October 13, 2016: Human Molecular Genetics
Peter T Campbell, Christina C Newton, Neal D Freedman, Jill Koshiol, Michael C Alavanja, Laura E Beane Freeman, Julie E Buring, Andrew T Chan, Dawn Q Chong, Mridul Datta, Mia M Gaudet, J Michael Gaziano, Edward L Giovannucci, Barry I Graubard, Albert R Hollenbeck, Lindsey King, I-Min Lee, Martha S Linet, Julie R Palmer, Jessica L Petrick, Jenny N Poynter, Mark P Purdue, Kim Robien, Lynn Rosenberg, Vikrant V Sahasrabuddhe, Catherine Schairer, Howard D Sesso, Alice J Sigurdson, Victoria L Stevens, Jean Wactawski-Wende, Anne Zeleniuch-Jacquotte, Andrew G Renehan, Katherine A McGlynn
Incidence rates for liver cancer have increased 3-fold since the mid-1970s in the United States in parallel with increasing trends for obesity and type II diabetes mellitus. We conducted an analysis of baseline body mass index (BMI), waist circumference (WC), and type II diabetes mellitus with risk of liver cancer. The Liver Cancer Pooling Project maintains harmonized data from 1.57 million adults enrolled in 14 U.S.-based prospective studies. Cox regression estimated HRs and 95% confidence intervals (CI) adjusted for age, sex, study center, alcohol, smoking, race, and BMI (for WC and type II diabetes mellitus)...
October 15, 2016: Cancer Research
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