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https://www.readbyqxmd.com/read/28645089/drug-resistance-mechanism-of-l10f-l10f-n88s-and-l90m-mutations-in-crf01_ae-hiv-1-protease-molecular-dynamics-simulations-and-binding-free-energy-calculations
#1
C S Vasavi, Ramasamy Tamizhselvi, Punnagai Munusami
HIV-1 protease plays a crucial role in viral replication and maturation, which makes it one of the most attractive targets for anti-retroviral therapy. The majority of HIV infections in developing countries are due to non-B subtype. Subtype AE is spreading rapidly and infecting huge population worldwide. The mutations in the active site of subtype AE directly impair the interactions with the inhibitor. The non-active site mutations influence the binding of the inhibitor indirectly and their resistance mechanism is not well understood...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28644686/cervical-adenocarcinoma-diagnosis-of-human-papillomavirus-positive-and-human-papillomavirus-negative-tumors
#2
Edyta C Pirog
CONTEXT: - Cervical adenocarcinomas span a diverse group of tumors with several distinct histologic tumor types, which include endocervical, endometrioid, intestinal, villoglandular, gastric, signet ring, serous, clear cell, and mesonephric. Diagnosis of cervical adenocarcinoma, especially early diagnosis, poses a significant challenge. OBJECTIVE: - To review the pathogenesis, diagnostic criteria, immunohistochemical markers, and differential diagnosis of various subtypes of human papillomavirus (HPV)-positive and HPV-negative cervical adenocarcinomas...
June 23, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28644418/new-mt%C3%A2-melatonin-receptor-selective-ligands-agonists-and-partial-agonists
#3
Jean A Boutin, Anne Bonnaud, Chantal Brasseur, Olivier Bruno, Nolwenn Lepretre, Peter Oosting, Sophie Coumailleau, Philippe Delagrange, Olivier Nosjean, Céline Legros
The search for melatonin receptor agonists and antagonists specific towards one of the receptor subtypes will extend our understanding of the role of this system in relaying circadian information to the body. A series of compounds derived from a hit compound discovered in a screening process led to powerful agonists specific for one of the isoform of the melatonin receptor namely, MT₂. The compounds are based on a poorly explored skeleton in the molecular pharmacology of melatonin. By changing the steric hindrance of one substituent (i...
June 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28644134/the-conundrum-of-the-epstein-barr-virus-associated-gastric-carcinoma-in-the-americas
#4
REVIEW
Gonzalo Carrasco-Avino, Ismael Riquelme, Oslando Padilla, Miguel Villaseca, Francisco R Aguayo, Alejandro H Corvalan
Epstein-Barr virus-associated gastric carcinoma shows a higher prevalence in the Americas than Asia. We summarize all studies of Epstein Barr virus-associated gastric carcinoma in the Americas, focusing on host characteristics, environmental associations and phylogeographic diversity of Epstein-Barr virus strains. In the Americas, the prevalence of Epstein Barr virus-associated gastric carcinoma is 11.4%, more frequent in males and portray predominantly diffuse-type histology. EBERs, EBNAs, BARTs and LMP are the highest expressed genes; their variations in healthy individuals may explain the phylogeographic diversity of Epstein-Barr virus across the region...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643426/cell-of-origin-classification-by-gene-expression-and-myc-rearrangements-in-diffuse-large-b-cell-lymphoma-of-children-and-adolescents
#5
Monika Szczepanowski, Jonas Lange, Christian W Kohler, Neus Masque-Soler, Martin Zimmermann, Sietse M Aukema, Michael Altenbuchinger, Thorsten Rehberg, Friederike Mahn, Reiner Siebert, Rainer Spang, Birgit Burkhardt, Wolfram Klapper
We present the largest series of diffuse large B-cell lymphoma (DLBCL) in patients younger than 18 years analysed to date by gene expression profiling using Nanostring technology to identify molecular subtypes and fluorescent in situ hybridization for translocations of MYC. We show that the activated B cell-like subtype of DLBCL is exceedingly rare in children and - in contrast to adults- not associated with outcome. Furthermore, we review the current literature and demonstrate that MYC translocations are not more frequent in paediatric compared to adult DLBCL...
June 23, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28642977/molecular-characteristics-and-prevalence-of-small-ruminant-lentiviruses-in-goats-in-japan
#6
Saki Kokawa, Mami Oba, Teppei Hirata, Shiro Tamaki, Miki Omura, Shinobu Tsuchiaka, Makoto Nagai, Tsutomu Omatsu, Tetsuya Mizutani
Small ruminant lentiviruses (SRLVs), which comprise caprine arthritis-encephalitis virus (CAEV) and maedi-visna virus (MVV), are prevalent in goats and sheep worldwide, including in Japan. However, little is known about the molecular characteristics of goat lentiviruses in Japan. In this study, a molecular and phylogenetic analysis of the long gag region was performed. The phylogenic tree demonstrated that all samples belonged to SRLV subtype B1. Two clusters were identified, with one cluster distinct from previously reported strains of subtype B1...
June 22, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28642756/high-prevalence-of-macrolide-resistance-and-molecular-characterization-of-streptococcus-pyogenes-isolates-circulating-in-china-from-2009-to-2016
#7
Binghuai Lu, Yujie Fang, Yanyan Fan, Xingchun Chen, Junrui Wang, Ji Zeng, Yi Li, Zhijun Zhang, Lei Huang, Hongxia Li, Dong Li, Fengxia Zhu, Yanchao Cui, Duochun Wang
Streptococcus pyogenes, or group A Streptococcus, is a pathogen responsible for a wide range of clinical manifestations, from mild skin and soft tissue infections and pharyngitis to severe diseases. Its epidemiological characteristics should be comprehensively under surveillance for regulating the national prevention and treatment practice. Herein, a total of 140 S. pyogenes, including 38 invasive and 102 noninvasive isolates, were collected from infected patients in 10 tertiary general hospitals from 7 cities/provinces in China during the years 2009-2016...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28642692/beyond-neuronal-activity-markers-select-immediate-early-genes-in-striatal-neuron-subtypes-functionally-mediate-psychostimulant-addiction
#8
REVIEW
Ramesh Chandra, Mary Kay Lobo
Immediate early genes (IEGs) were traditionally used as markers of neuronal activity in striatum in response to stimuli including drugs of abuse such as psychostimulants. Early studies using these neuronal activity markers led to important insights in striatal neuron subtype responsiveness to psychostimulants. Such studies have helped identify striatum as a critical brain center for motivational, reinforcement and habitual behaviors in psychostimulant addiction. While the use of IEGs as neuronal activity markers in response to psychostimulants and other stimuli persists today, the functional role and implications of these IEGs has often been neglected...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28642594/differential-effects-on-gene-transcription-and-hematopoietic-differentiation-correlate-with-gata2-mutant-disease-phenotypes
#9
C-E Chong, P Venugopal, P H Stokes, Y K Lee, P J Brautigan, D T O Yeung, M Babic, G A Engler, S W Lane, M Klingler-Hoffmann, J M Matthews, R J D'Andrea, A L Brown, C N Hahn, H S Scott
Heterozygous GATA2 mutations underlie an array of complex hematopoietic and lymphatic diseases. Analysis of the literature reporting three recurrent GATA2 germline (g) mutations (gT354M, gR396Q, gR398W) revealed different phenotype tendencies. While all three mutants differentially predispose to myeloid malignancies, there was no difference in leukemia-free survival for GATA2 patients. Despite intense interest, the molecular pathogenesis of GATA2 mutation is poorly understood. We functionally characterized a GATA2 mutant allelic series representing major disease phenotypes caused by germline and somatic (s) mutations in zinc finger (ZF) 2...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28642461/the-ca19-9-and-sialyl-tra-antigens-define-separate-subpopulations-of-pancreatic-cancer-cells
#10
Daniel Barnett, Ying Liu, Katie Partyka, Ying Huang, Huiyuan Tang, Galen Hostetter, Randall E Brand, Aatur D Singhi, Richard R Drake, Brian B Haab
Molecular markers to detect subtypes of cancer cells could facilitate more effective treatment. We recently identified a carbohydrate antigen, named sTRA, that is as accurate a serological biomarker of pancreatic cancer as the cancer antigen CA19-9. We hypothesized that the cancer cells producing sTRA are a different subpopulation than those producing CA19-9. The sTRA glycan was significantly elevated in tumor tissue relative to adjacent pancreatic tissue in 3 separate tissue microarrays covering 38 patients...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642303/molecular-analysis-of-myelodysplastic-syndrome-with-isolated-del-5q-reveals-a-specific-spectrum-of-molecular-mutations-with-prognostic-impact-a-study-on-123-patients-and-27-genes
#11
Manja Meggendorfer, Claudia Haferlach, Wolfgang Kern, Torsten Haferlach
The only cytogenetic aberration defining a myelodysplastic syndrome subtype is the deletion of the long arm of chromosome 5, giving with morphological features the diagnosis of myelodysplastic syndrome with isolated del(5q). These patients show a good prognosis and respond to treatment such as lenalidomide, but some cases progress to acute myeloid leukemia. However, the molecular mutation pattern is rarely characterized. Therefore, we investigated a large cohort of 123 myelodysplastic syndrome patients with isolated del(5q) diagnosed following the World Health Organization classifications 2008 and 2016 by sequencing 27 genes...
June 22, 2017: Haematologica
https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#12
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28640243/in-depth-investigations-of-adolescents-and-adults-with-holoprosencephaly-identify-unique-characteristics
#13
Karin Weiss, Paul Kruszka, Maria J Guillen Sacoto, Yonit A Addissie, Donald W Hadley, Casey K Hadsall, Bethany Stokes, Ping Hu, Erich Roessler, Beth Solomon, Edythe Wiggs, Audrey Thurm, Robert B Hufnagel, Wadih M Zein, Jin S Hahn, Elaine Stashinko, Eric Levey, Debbie Baldwin, Nancy J Clegg, Mauricio R Delgado, Maximilian Muenke
PurposeWith improved medical care, some individuals with holoprosencephaly (HPE) are surviving into adulthood. We investigated the clinical manifestations of adolescents and adults with HPE and explored the underlying molecular causes.MethodsParticipants included 20 subjects 15 years of age and older. Clinical assessments included dysmorphology exams, cognitive testing, swallowing studies, ophthalmic examination, and brain magnetic resonance imaging. Genetic testing included chromosomal microarray, Sanger sequencing for SHH, ZIC2, SIX3, and TGIF, and whole-exome sequencing (WES) of 10 trios...
June 22, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28639053/managing-the-genomic-revolution-in-cancer-diagnostics
#14
Doreen Nguyen, Christopher D Gocke
Molecular tumor profiling is now a routine part of patient care, revealing targetable genomic alterations and molecularly distinct tumor subtypes with therapeutic and prognostic implications. The widespread adoption of next-generation sequencing technologies has greatly facilitated clinical implementation of genomic data and opened the door for high-throughput multigene-targeted sequencing. Herein, we discuss the variability of cancer genetic profiling currently offered by clinical laboratories, the challenges of applying rapidly evolving medical knowledge to individual patients, and the need for more standardized population-based molecular profiling...
June 21, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28638726/downregulation-of-antigen-presentation-associated-pathway-proteins-is-linked-to-poor-outcome-in-triple-negative-breast-cancer-patient-tumors
#15
Martin H Pedersen, Brian L Hood, Hans Christian Beck, Thomas P Conrads, Henrik J Ditzel, Rikke Leth-Larsen
Triple-negative breast cancer (TNBC) is a heterogeneous subtype with varying disease outcomes. Tumor-infiltrating lymphocytes (TILs) are frequent in TNBC and have been shown to correlate with outcome, suggesting an immunogenic component in this subtype. However, other factors intrinsic to the cancer cells may also influence outcome. To identify proteins and molecular pathways associated with recurrence in TNBC, 34 formalin-fixed paraffin-embedded (FFPE) primary TNBC tumors were investigated by global proteomic profiling using mass spectrometry...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28638582/an-overview-of-inflammatory-bowel-disease-general-consideration-and-genetic-screening-approach-in-diagnosis-of-early-onset-subsets
#16
REVIEW
Shahram Nemati, Shahram Teimourian
Inflammatory bowel disease (IBD) is the consequence of an aberrant hemostasis of the immune cells at the gut mucosal border. Based on clinical manifestation, laboratory tests, radiological studies, endoscopic and histological features, this disease is divided into three main types including Crohn's disease (CD), Ulcerative colitis (UC), and IBDunclassified (IBD-U). IBD is frequently presented in adults, but about 20% of IBD cases are diagnosed during childhood called pediatric IBD (PIBD). Some patients in the latter group emerge the first symptoms during infancy or under 5 years of age named infantile and very early onset IBD (VEO-IBD), respectively...
April 2017: Middle East Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28638113/clinical-significance-and-next-generation-sequencing-of-chinese-pulmonary-sarcomatoid-carcinoma
#17
Xin Li, Dan Wang, Qingchun Zhao, Dian Ren, Fan Ren, Gang Chen, Hongyu Liu, Jun Chen
Pulmonary Sarcomatoid Carcinoma (PSC) constitutes a heterogeneous group of non-small-cell lung carcinomas (NSCLCs) with a poor prognosis. In this study, a group of 7 patients with PSC was studied. Microscope analysis of all 7 cases revealed a pleomorphic carcinoma subtype. Moreover, 5 cases (71.4%) were composed entirely of malignant sarcomatoid-like elements, and 2 cases (28.6%) were composed of malignant sarcomatoid-like elements and at least 10% adenocarcinoma-like elements. Immunohistochemically, the PSC components of all 7 cases were positive for vimentin and cytokeratins, including cytokeratin (CK) and cytokeratin 7 (CK7)...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28635667/a-review-of-flaviviruses-that-have-no-known-arthropod-vector
#18
REVIEW
Bradley J Blitvich, Andrew E Firth
Most viruses in the genus Flavivirus are horizontally transmitted between hematophagous arthropods and vertebrate hosts, but some are maintained in arthropod- or vertebrate-restricted transmission cycles. Flaviviruses maintained by vertebrate-only transmission are commonly referred to as no known vector (NKV) flaviviruses. Fourteen species and two subtypes of NKV flaviviruses are recognized by the International Committee on Taxonomy of Viruses (ICTV), and Tamana bat virus potentially belongs to this group. NKV flaviviruses have been isolated in nature almost exclusively from bats and rodents; exceptions are the two isolates of Dakar bat virus recovered from febrile humans and the recent isolations of Sokoluk virus from field-collected ticks, which raises questions as to whether it should remain classified as an NKV flavivirus...
June 21, 2017: Viruses
https://www.readbyqxmd.com/read/28634007/gene-expression-differences-between-ductal-carcinoma-in-situ-with-and-without-progression-to-invasive-breast-cancer
#19
Shusma C Doebar, Anieta M Sieuwerts, Vanja de Weerd, Hans Stoop, John W M Martens, Carolien H M van Deurzen
To understand the molecular alterations driving the progression of ductal carcinoma in situ (DCIS), we compared patients with pure DCIS and patients with DCIS and synchronous invasive breast cancer (IBC). Twelve patients with extensive pure DCIS were included as a representation of indolent lesions with limited invasive capacity. These cases were matched with 12 patients with a limited DCIS component and IBC, representing lesions with a high invasive potential. Matching included age and surrogate DCIS subtypes...
July 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28633944/gene-expression-analysis-identify-a-metabolic-and-cell-function-alterations-as-a-hallmark-of-obesity-without-metabolic-syndrome-in-peripheral-blood-a-pilot-study
#20
Daniel Antonio de Luis, Raquel Almansa, Rocío Aller, Olatz Izaola, E Romero
BACKGROUND: Understanding molecular basis involved in overweight is an important first step in developing therapeutic pathways against excess in body weight gain. OBJECTIVE: The purpose of our pilot study was to evaluate the gene expression profiles in the peripheral blood of obese patients without other metabolic complications. DESIGN: A sample of 17 obese patients without metabolic syndrome and 15 non obese control subjects was evaluated in a prospective way...
June 10, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
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