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Consensus molecular

Bartlomiej Tywoniuk, Ye Yuan, Sarah McCartan, Beata Maria Szydlowska, Florentina Tofoleanu, Bernard R Brooks, Nicolae-Viorel Buchete
Nanoscale fibrils formed by amyloid peptides have a polymorphic character, adopting several types of molecular structures in similar growth conditions. This property, evidenced in both experimental (i.e., solid state NMR) and computational studies, hinders both the structural characterization of Alzheimer's Aβ amyloid protofilaments and fibrils at a molecular level, as well as the possible applications (i.e., development of drugs or biomarkers) that rely on similar, controlled molecular arrangements of the Aβ peptides in amyloid fibril structures...
October 18, 2018: Journal of Physical Chemistry. B
Erica CIrri, Sébastien Brier, Reda Assal, Juan Carlos Canul-Tec, Julia Chamot-Rooke, Nicolas Reyes
Human excitatory amino acid transporters (EAATs) take up the neurotransmitter glutamate in the brain and are essential to maintain excitatory neurotransmission. Our understanding of the EAATs' molecular mechanisms has been hampered by the lack of stability of purified protein samples for biophysical analyses. Here, we present approaches based on consensus mutagenesis to obtain thermostable EAAT1 variants that share up to ~ 95% amino acid identity with the wild type transporters, and remain natively folded and functional...
October 18, 2018: ELife
Tibor Magyar, Éva Gyuris, Barbara Ujvári, Martin Metzner, Enikő Wehmann
Riemerella anatipestifer (RA) is a widely distributed bacterial pathogen of birds responsible for remarkable losses to poultry production, especially among waterfowl. We characterized the genomic diversity of 166 field isolates of RA collected from geese and ducks using enterobacterial repetitive intergenic consensus (ERIC)-polymerase chain reaction (PCR). The field strains and five reference strains showed 17 distinct patterns consisting of five to 12 bands ranging from approximately150-1800bp. The majority of the strains belonged to two closely related ERIC-PCR types (A and B), while the other types contained only a few isolates each...
October 17, 2018: Avian Pathology: Journal of the W.V.P.A
Irene Lacal, Rossella Ventura
Parents' stressful experiences can influence an offspring's vulnerability to many pathological conditions, including psychopathologies, and their effects may even endure for several generations. Nevertheless, the cause of this phenomenon has not been determined, and only recently have scientists turned to epigenetics to answer this question. There is extensive literature on epigenetics, but no consensus exists with regard to how and what can (and must) be considered to study and define epigenetics processes and their inheritance...
2018: Frontiers in Molecular Neuroscience
Michele Carbone, Ivano Amelio, El Bachir Affar, James Brugarolas, Lisa A Cannon-Albright, Lewis C Cantley, Webster K Cavenee, Zhijian Chen, Carlo M Croce, Alan D' Andrea, David Gandara, Carlotta Giorgi, Wei Jia, Qing Lan, Tak Wah Mak, James L Manley, Katsuhiko Mikoshiba, Jose N Onuchic, Harvey I Pass, Paolo Pinton, Carol Prives, Nathaniel Rothman, Said M Sebti, James Turkson, Xifeng Wu, Haining Yang, Herbert Yu, Gerry Melino
The relative contribution of intrinsic genetic factors and extrinsic environmental ones to cancer aetiology and natural history is a lengthy and debated issue. Gene-environment interactions (G x E) arise when the combined presence of both a germline genetic variant and a known environmental factor modulates the risk of disease more than either one alone. A panel of experts discussed our current understanding of cancer aetiology, known examples of G × E interactions in cancer, and the expanded concept of G × E interactions to include somatic cancer mutations and iatrogenic environmental factors such as anti-cancer treatment...
October 15, 2018: Cell Death and Differentiation
Yangyang Li, Baixing Wu, Hehua Liu, Yanqing Gao, Chun Yang, Xi Chen, Jing Zhang, Yiqing Chen, Yijun Gu, Jixi Li, Jinbiao Ma, Jianhua Gan
DUX4 plays critical role in the molecular pathogenesis of the neuromuscular disorder facioscapulohumeral muscular dystrophy and acute lymphoblastic leukemia in humans. As a master transcription regulator, DUX4 can also bind the promoters and activate the transcription of hundreds ZGA-associated genes. Here we report on the structural and biochemical studies of DUX4 double homeodomains (DUX4-DH), representing the only structures contain both homeodomain 1 (HD1) and homeodomain 2 (HD2). HD1 and HD2 adopt classical homeobox fold; via the helix inserted into the major groove and the N-terminal extended loop inserted into the minor groove, HD1 and HD2 recognize the box1 (5'-TAA-3') and box2 (5'-TGA-3') nucleotides of the consensus sequence, respectively...
October 12, 2018: Biochemical and Biophysical Research Communications
Habib Zaidi, Abass Alavi, Issam El Naqa
Quantitative image analysis has deep roots in the usage of positron emission tomography (PET) in clinical and research settings to address a wide variety of diseases. It has been extensively employed to assess molecular and physiological biomarkers in vivo in healthy and disease states, in oncology, cardiology, neurology, and psychiatry. Quantitative PET allows relating the time-varying activity concentration in tissues/organs of interest and the basic functional parameters governing the biological processes being studied...
November 2018: Seminars in Nuclear Medicine
Jessica L Mester, Rajarshi Ghosh, Tina Pesaran, Robert Huether, Rachid Karam, Kathleen S Hruska, Helio A Costa, Katherine Lachlan, Joanne Ngeow, Jill Barnholtz-Sloan, Kaitlin Sesock, Felicia Hernandez, Liying Zhang, Laura Milko, Sharon E Plon, Madhuri Hegde, Charis Eng
The ClinGen PTEN Expert Panel was organized by the ClinGen Hereditary Cancer Clinical Domain Working Group to assemble clinicians, researchers, and molecular diagnosticians with PTEN expertise to develop specifications to the 2015 ACMG/AMP Sequence Variant Interpretation Guidelines for PTEN variant interpretation. We describe finalized PTEN-specific variant classification criteria and outcomes from pilot testing of 42 variants with benign/likely benign (BEN/LBEN), pathogenic/likely pathogenic (PATH/LPATH), uncertain significance (VUS), and conflicting (CONF) ClinVar assertions...
November 2018: Human Mutation
Gordan M Vujanić, Manfred Gessler, Ariadne H A G Ooms, Paola Collini, Aurore Coulomb-l'Hermine, Ellen D'Hooghe, Ronald R de Krijger, Daniela Perotti, Kathy Pritchard-Jones, Christian Vokuhl, Marry M van den Heuvel-Eibrink, Norbert Graf
On the basis of the results of previous national and international trials and studies, the Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP-RTSG) has developed a new study protocol for paediatric renal tumours: the UMBRELLA SIOP-RTSG 2016 protocol (the UMBRELLA protocol). Currently, the overall outcomes of patients with Wilms tumour are excellent, but subgroups with poor prognosis and increased relapse rates still exist. The identification of these subgroups is of utmost importance to improve treatment stratification, which might lead to reduction of the direct and late effects of chemotherapy...
October 11, 2018: Nature Reviews. Urology
Natalie Galanina, Razelle Kurzrock
BACKGROUND: The treatment of peripheral T-cell lymphoma (PTCL) after failure of standard therapy represents a significant clinical challenge as the best approach has not been defined. The outcomes of patients with peripheral T-cell lymphoma (PTCL) after relapse, in the absence of hematopoietic stem-cell transplantation, are poor with median overall survival is less than six months. Thus, relapsed/refractory PTCL presents an area of unmet medical need. CASE PRESENTATION: Herein, we report an 84-year old woman with stage IV PTCL with extensive involvement of the bowel and abdominal pain...
October 11, 2018: Cancer Biology & Therapy
M Vall-Palomar, J Arévalo, G Ariceta, A Meseguer
BACKGROUND: Molecular and cellular pathophysiological events occurring in the majority of rare kidney diseases remain to be elucidated. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder caused by mutations in either CLDN16 or CLDN19 genes. This disease is characterized by massive urinary wasting of magnesium and calcium, osmosis deregulation and polyuria. Patients with p.G20D homozygous mutation in CLDN19 gene exhibit different progression to kidney failure suggesting that beyond the pathogenic mutation itself, other molecular events are favoring disease progression...
October 11, 2018: Journal of Translational Medicine
Akram Azimi, Amir Peymani, Parham Kianoush Pour
INTRODUCTION: Health care-associated infections caused by metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa are a significant growing concern in patients with burns worldwide. The aims of this study were to determine the antibiotic susceptibility of and detect the presence of MBLs among P. aeruginosa isolates and assess their clonal relationship using enterobacterial repetitive intergenic consensus (ERIC)-PCR. METHODS: Non-duplicated clinical isolates (160) of P...
September 2018: Revista da Sociedade Brasileira de Medicina Tropical
Didier Frappaz, Cécile Faure-Conter, David Meyronet, Alice Levard-Bonneville, Pierre-Aurélien Beuriat, Marie P Sunyach, Marc Barritault
PURPOSE OF REVIEW: Medulloblastoma is no more a unique disease. Clinical and biologic classification used so far are challenged by molecular classification(s). Following the consensus article that described four molecular groups of medulloblastoma in 2012, several articles in 2017 provided more relevant classifications that may impact on further clinical trial design. RECENT FINDINGS: Though wingless (WNT) and sonic hedgehog (SHH) are defined by the activation of their respective pathways, the age and type of activation define various subgroups with specific features and outcome...
October 8, 2018: Current Opinion in Neurology
Edward Faught, Ioannis Karakis, Daniel L Drane
PURPOSE OF REVIEW: Our purpose is to review evidence relating to the concept that interictal epileptiform discharges (IEDs) impair brain performance. RECENT FINDINGS: Sophisticated measures of motor and cognitive performance have clarified older observations, confirming that in both animals and humans, IEDs affect aspects of performance, IED morphology, frequency, anatomical distribution, and duration matter. However, we now know that it is difficult to draw a line between IEDs and seizures, not only by electrical criteria but even by metabolic and molecular measures...
October 8, 2018: Current Neurology and Neuroscience Reports
Alexandre M Erkine
The transcriptional activation domains (TADs) are critical for life, yet intrinsically disordered polypeptides with no specific consensus sequence, interacting with multiple targets via low-specificity fuzzy contacts. The recent integration of machine learning approaches in biochemistry allows analysis of large experimental datasets of functional TADs as a whole and clear observation of TAD features. The emerging picture describes TADs as sequences without consensus but with a variety of detergent-like mini-motifs enriched in negatively charged and aromatic amino acids...
October 5, 2018: Trends in Biochemical Sciences
Rachel E Simpson, Nathan J Cockerill, Michele T Yip-Schneider, Eugene P Ceppa, Michael G House, Nicholas J Zyromski, Attila Nakeeb, Mohammad A Al-Haddad, C M Schmidt
BACKGROUND: For pancreatic cysts with negative cytology, Integrated Molecular Pathology (IMP) is a malignancy risk score integrating clinical criteria with pancreatic cyst fluid DNA profiling. Aside from main pancreatic duct (MPD) diameter, integrated clinical criteria are not International Consensus Guidelines High-Risk Stigmata. We predicted exclusion of clinical criteria except MPD diameter could simplify the IMP and better distinguish invasive/malignant disease. METHODS: Records of >1100 patients with IPMN were reviewed retrospectively...
October 4, 2018: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
Trust Saidi, Jill Fortuin, Tania S Douglas
BACKGROUND: The emergence of nanomedicine in the past decade has changed the landscape of disease diagnosis and treatment. Nanomedicine makes use of nanostructures for applications in different fields of medicine, including drug delivery, biosensors, neuro-electronic interfaces, in vivo imaging, and cell-specific molecular interactions. Despite its relative infancy, nanomedicine has generated a significant body of research as evidenced by peer reviewed literature and several patents. This proposed systematic review will focus specifically on drug delivery systems in which nanoparticles are used to enhance the pharmacological and therapeutic properties of drugs...
October 6, 2018: Systematic Reviews
Dominiek Smeets, Ian S Miller, Darran P O'Connor, Sudipto Das, Bruce Moran, Bram Boeckx, Timo Gaiser, Johannes Betge, Ana Barat, Rut Klinger, Nicole C T van Grieken, Chiara Cremolini, Hans Prenen, Massimiliano Mazzone, Jeroen Depreeuw, Orna Bacon, Bozena Fender, Joseph Brady, Bryan T Hennessy, Deborah A McNamara, Elaine Kay, Henk M Verheul, Neerincx Maarten, William M Gallagher, Verena Murphy, Jochen H M Prehn, Miriam Koopman, Cornelis J A Punt, Fotios Loupakis, Matthias P A Ebert, Bauke Ylstra, Diether Lambrechts, Annette T Byrne
Increased copy number alterations (CNAs) indicative of chromosomal instability (CIN) have been associated with poor cancer outcome. Here, we study CNAs as potential biomarkers of bevacizumab (BVZ) response in metastatic colorectal cancer (mCRC). We cluster 409 mCRCs in three subclusters characterized by different degrees of CIN. Tumors belonging to intermediate-to-high instability clusters have improved outcome following chemotherapy plus BVZ versus chemotherapy alone. In contrast, low instability tumors, which amongst others consist of POLE-mutated and microsatellite-instable tumors, derive no further benefit from BVZ...
October 5, 2018: Nature Communications
Wenxi Yu, Maiya Yu, Makaía M Papasergi-Scott, Gregory G Tall
Resistance to Inhibitors of Cholinesterase-8 (Ric-8) proteins are molecular chaperones that fold heterotrimeric G protein α subunits shortly after biosynthesis. Ric-8 proteins also act as test tube guanine nucleotide exchange factors (GEF) that promote Gα subunit GDP for GTP exchange. The GEF and chaperoning activities of Ric-8A are regulated by phosphorylation of five serine and threonine residues within protein kinase CK2 consensus sites. The traditional way that Ric-8A proteins have been purified is from Spodoptera frugiperda (Sf9) or Trichoplusia ni (Tni) insect cells...
October 2, 2018: Protein Expression and Purification
Silvia Halim, Elke K Markert, Alexei Vazquez
BACKGROUND: Human cancers can be classified based on gene signatures quantifying the degree of cell proliferation and tissue remodelling (PR). However, the specific factors that drive the increased tissue remodelling in tumours are not fully understood. Here we address this question using colorectal cancer as a case study. METHODS: We reanalysed a reported cohort of colorectal cancer patients. The patients were stratified based on gene signatures of cell proliferation and tissue remodelling...
October 2018: British Journal of Cancer
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