keyword
MENU ▼
Read by QxMD icon Read
search

Mutational load

keyword
https://www.readbyqxmd.com/read/29148538/molecular-testing-for-braf-mutations-to-inform-melanoma-treatment-decisions-a-move-toward-precision-medicine
#1
Liang Cheng, Antonio Lopez-Beltran, Francesco Massari, Gregory T MacLennan, Rodolfo Montironi
Approximately one-half of advanced (unresectable or metastatic) melanomas harbor a mutation in the BRAF gene, with V600E being the most common mutation. Targeted therapy with BRAF and MEK inhibitors is associated with significant long-term treatment benefit in patients with BRAF V600-mutated melanoma. Therefore, molecular testing for BRAF mutations is a priority in determining the course of therapy. A literature search was performed using MEDLINE/PubMed and scientific congress databases using the terms 'BRAF,' 'mutation,' and 'cancer/tumor...
November 17, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29142126/hpv-replication-regulation-by-acetylation-of-a-conserved-lysine-in-the-e2-protein
#2
Yanique Thomas, Elliot J Androphy
The Papillomavirus (PV) E2 protein is a sequence specific DNA binding protein that recruits cellular factors to its genome in infected epithelial cells. E2 also binds to and loads the viral E1 DNA helicase at the origin of replication. Post-translational modifications (PTMs) of PV E2 have been identified as potential regulators E2 functions. We recently reported lysine (K) 111 as a target of p300 acetylation in bovine (B)PV. The di-lysines at 111 and 112 are conserved in almost all papillomaviruses. We pursued a mutational approach to query the functional significance of lysine in human (H)PV E2...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142072/salt-bridges-gate-alpha-catenin-activation-at-intercellular-junctions
#3
Samantha Barrick, Jing Li, Xinyu Kong, Alokananda Ray, Emad Tajkhorshid, Deborah Leckband
Cadherin complexes transduce force fluctuations at junctions to activate signals that reinforce stressed intercellular contacts. α-Catenin is an identified force transducer within cadherin complexes that is autoinhibited under low tension. Increased force triggers a conformational change that exposes a cryptic site for the actin-binding protein vinculin. This study tested predictions that salt bridges within the force-sensing core modulate α-catenin activation. Studies with a fluorescence resonance energy transfer (FRET)-based α-catenin conformation sensor demonstrated that the salt-bridge mutations R551A and D503N each enhance α-catenin activation in live cells, but R551A has a greater impact...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29136032/virological-response-and-resistance-among-hiv-infected-children-receiving-long-term-antiretroviral-therapy-without-virological-monitoring-in-uganda-and-zimbabwe-observational-analyses-within-the-randomised-arrow-trial
#4
Alexander J Szubert, Andrew J Prendergast, Moira J Spyer, Victor Musiime, Philippa Musoke, Mutsa Bwakura-Dangarembizi, Patricia Nahirya-Ntege, Margaret J Thomason, Emmanuel Ndashimye, Immaculate Nkanya, Oscar Senfuma, Boniface Mudenge, Nigel Klein, Diana M Gibb, A Sarah Walker
BACKGROUND: Although WHO recommends viral load (VL) monitoring for those on antiretroviral therapy (ART), availability in low-income countries remains limited. We investigated long-term VL and resistance in HIV-infected children managed without real-time VL monitoring. METHODS AND FINDINGS: In the ARROW factorial trial, 1,206 children initiating ART in Uganda and Zimbabwe between 15 March 2007 and 18 November 2008, aged a median 6 years old, with median CD4% of 12%, were randomised to monitoring with or without 12-weekly CD4 counts and to receive 2 nucleoside reverse transcriptase inhibitors (2NRTI, mainly abacavir+lamivudine) with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or 3 NRTIs as long-term ART...
November 2017: PLoS Medicine
https://www.readbyqxmd.com/read/29132466/-association-of-drug-resistance-of-mycoplasma-pneumoniae-with-dna-load-and-genotypes-in-children-with-mycoplasma-pneumoniae-pneumonia
#5
Hui-Fen Zhang, Hai-Tao Bai, Ji-Ming Li, Hui Xie, Ye Wang
OBJECTIVE: To investigate the association of drug resistance of Mycoplasma pneumoniae (MP) with DNA load and genotypes in children with MP pneumonia. METHODS: A total of 230 children who were hospitalized and diagnosed with MP pneumonia between January 2012 and December 2016 were enrolled. Throat swabs were collected from the 230 children, and a rapid drug sensitivity assay was used to determine the sensitivity of clinical isolates of MP to nine commonly used antibacterial agents...
November 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29130659/-dna-repair-function-and-mutation-of-an-h2b-monoubiquitination-factor-wdr70-in-ovarian-cancer
#6
Zi-Zhi Tang, Hai-Bin Wang, Ming Zeng, Cong Liu, De-Hua Li
OBJECTIVE: To investigate the roles of enzyme DCAF proteinDNA damagebinding protein 1 (DDB1)/cullin4 (CRL4) complex family members CRL4WD40 repeat domain protein 70 (WDR70) in DNA repair process and its mutation in ovarian cancer. METHODS: Immunofluorescent assay was employed to measure H2AX (γH2AX) and phosphorylated replication protein A2 (RPA32) formed in siDDB1 or siWDR70 ovarian cancer cells after the treatments of chemical medicine and radioactive threapy...
September 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/29129521/diffusion-tensor-imaging-and-magnetic-resonance-spectroscopy-in-a-patient-with-adult-onset-tuberous-sclerosis-complex
#7
Hidehiro Ishikawa, Atsushi Niwa, Masaru Asahi, Keita Matsuura, Satoshi Masuzugawa, Yo Niida, Masayuki Maeda, Mineo Kondo, Hidekazu Tomimoto
Tuberous sclerosis complex (TSC) 1 or TSC2 is mutated in most TSC patients. TSC2 mutations are more frequently associated with worse outcomes, earlier age at seizure onset, more severe intellectual disability, and higher tuber load than TSC1. The degree of white matter involvement is thought to be associated with the severity of neurological impairment. At present, genotype-phenotype correlations and relationship between tuber burden and neurological disability in TSC are debatable. We presented a 43-year-old patient with TSC2 mutation, whose symptom was only incomplete quadrantic visual field deficit in spite of multiple brain tubers...
November 9, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29128646/hiv-drug-resistance-following-a-decade-of-free-antiretroviral-therapy-program-in-india-a-review
#8
REVIEW
Santosh Karade, Devidas N Chaturbhuj, Sourav Sen, Rajneesh K Joshi, Smita S Kulkarni, Subramanian Shankar, Raman R Gangakhedkar
OBJECTIVE: The objective of this review is to assess the burden of HIV drug resistance mutations (DRM) in Indian adults exposed to first-line ART as per national guidelines. METHODS: We performed advanced search for the published literature on HIV drug resistance in India in PubMed and Scopus. From each publication data pertaining to age, sex, CD4 count and viral load, prevalence of NRTI/NNRTI drug resistance mutations (DRM) was extracted. Year-wise Indian HIV-1 reverse transcriptase (RT) sequences were retrieved from Los Alamos HIV database and mutation analyses were performed...
November 8, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/29126456/virological-response-hiv-1-drug-resistance-mutations-and-genetic-diversity-among-patients-on-first-line-antiretroviral-therapy-in-n-djamena-chad-findings-from-a-cross-sectional-study
#9
Chatté Adawaye, Joseph Fokam, Erick Kamangu, Hamit Mahamat Alio, Aoudalkarim Moussa Chahad, Fabrice Susin, Ali Mahamat Moussa, Tchombou Hig-Zounet Bertin, Abdelsalam Tidjani, Dolores Vaira, Michel Moutschen
BACKGROUND: The national antiretroviral therapy in the Republic of Chad provides free of charge antiretroviral regimens and therapeutic monitoring for patients receiving antiretroviral therapy nationwide. For a successful programmatic uptake, these efforts merit to be supported by thorough assessments of antiretroviral therapy response and HIV-1 drug resistance surveillance, especially with risks of cross-resistance due to the gradual stavudine phasing out in such national settings. We therefore evaluated the virological response to antiretroviral therapy, HIV-1 drug resistance emergence and circulating HIV-1 clades in a Chad context...
November 10, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29126427/a-murine-model-for-developmental-dysplasia-of-the-hip-ablation-of-cx3cr1-affects-acetabular-morphology-and-gait
#10
George Feldman, Arlene Offemaria, Hind Sawan, Javad Parvizi, Theresa A Freeman
BACKGROUND: Developmental dysplasia of the hip (DDH) is a debilitating condition whose distinguishing signs include incomplete formation of the acetabulum leading to dislocation of the femur, accelerated wear of the articular cartilage and joint laxity resulting in osteoarthritis. It is a complex disorder having environmental and genetic causes. Existing techniques fail to detect milder forms of DDH in newborns leading to hip osteoarthritis in young adults. A sensitive, specific and cost effective test would allow identification of newborns that could be non-invasively corrected by the use of a Pavlik harness...
November 10, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29124790/neuropathology-of-genetic-synucleinopathies-with-parkinsonism-review-of-the-literature
#11
REVIEW
Susanne A Schneider, Roy N Alcalay
Clinical-pathological studies remain the gold-standard for the diagnosis of Parkinson's disease (PD). However, mounting data from genetic PD autopsies challenge the diagnosis of PD based on Lewy body pathology. Most of the confirmed genetic risks for PD show heterogenous neuropathology, even within kindreds, which may or may not include Lewy body pathology. We review the literature of genetic PD autopsies from cases with molecularly confirmed PD or parkinsonism and summarize main findings on SNCA (n = 25), Parkin (n = 20, 17 bi-allelic and 3 heterozygotes), PINK1 (n = 5, 1 bi-allelic and 4 heterozygotes), DJ-1 (n = 1), LRRK2 (n = 55), GBA (n = 10 Gaucher disease patients with parkinsonism), DNAJC13, GCH1, ATP13A2, PLA2G6 (n = 8 patients, 2 with PD), MPAN (n = 2), FBXO7, RAB39B, and ATXN2 (SCA2), as well as on 22q deletion syndrome (n = 3)...
November 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29123471/vglut2-trafficking-is-differentially-regulated-by-adaptor-proteins-ap-1-and-ap-3
#12
Haiyan Li, Magda S Santos, Chihyung K Park, Yuriy Dobry, Susan M Voglmaier
Release of the major excitatory neurotransmitter glutamate by synaptic vesicle exocytosis depends on glutamate loading into synaptic vesicles by vesicular glutamate transporters (VGLUTs). The two principal isoforms, VGLUT1 and 2, exhibit a complementary pattern of expression in adult brain that broadly distinguishes cortical (VGLUT1) and subcortical (VGLUT2) systems, and correlates with distinct physiological properties in synapses expressing these isoforms. Differential trafficking of VGLUT1 and 2 has been suggested to underlie their functional diversity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29120748/doubling-down-on-brca-mutated-cancer
#13
Andrea E Wahner Hendrickson, Scott H Kaufmann, Elizabeth M Swisher
Immunotherapy is changing the landscape of cancer treatment. Nonetheless, not all malignancies respond, possibly due to low mutational load. Recent work in a TP53(-/-)BRCA1-mutant murine breast cancer model indicates that double blockade with two immune checkpoint inhibitors increases the number of tumor-infiltrating lymphocytes and overall survival after DNA damaging chemotherapy, whereas single blockade does not. These findings suggest an approach to enhance the impact of immune checkpoint blockade in BRCA-mutated tumors...
November 2017: Trends in Cancer
https://www.readbyqxmd.com/read/29118134/temperature-effects-on-life-history-trade-offs-germline-maintenance-and-mutation-rate-under-simulated-climate-warming
#14
David Berger, Josefine Stångberg, Karl Grieshop, Ivain Martinossi-Allibert, Göran Arnqvist
Mutation has a fundamental influence over evolutionary processes, but how evolutionary processes shape mutation rate remains less clear. In asexual unicellular organism, increased mutation rates have been observed in stressful environments and the reigning paradigm ascribes this increase to selection for evolvability. However, this explanation does not apply in sexually reproducing species, where little is known about how the environment affects mutation rate. Here we challenged experimental lines of seed beetle, evolved at ancestral temperature or under simulated climate warming, to repair induced mutations at ancestral and stressful temperature...
November 15, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/29117571/single-cell-virology-on-chip-investigation-of-viral-infection-dynamics
#15
Feng Guo, Sixing Li, Mehmet Umut Caglar, Zhangming Mao, Wu Liu, Andrew Woodman, Jamie J Arnold, Claus O Wilke, Tony Jun Huang, Craig E Cameron
We have developed a high-throughput, microfluidics-based platform to perform kinetic analysis of viral infections in individual cells. We have analyzed thousands of individual poliovirus infections while varying experimental parameters, including multiplicity of infection, cell cycle, viral genotype, and presence of a drug. We make several unexpected observations masked by population-based experiments: (1) viral and cellular factors contribute uniquely and independently to viral infection kinetics; (2) cellular factors cause wide variation in replication start times; and (3) infections frequently begin later and replication occurs faster than predicted by population measurements...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29111583/from-peptide-fragments-to-whole-protein-copper-ii-load-and-coordination-features-of-iapp
#16
Antonio Magrì, Adriana Pietropaolo, Giovanni Tabbì, Diego La Mendola, Enrico Rizzarelli
The copper binding features of rat islet amyloid polypeptide (r-IAPP) are herein disclosed through the determination of the stability constants and spectroscopic properties of its copper complex species. To mimic the metal binding sites of the h-IAPP, a soluble, single point mutated having a histidine residue in place of Arg18 was synthesized, i.e. r-IAPP(1-37;R18H). The peptide IAPP(1-8) was also characterized to have deeper insight into the N-terminus copper(II) binding features of r-IAPP as well as of its mutated form...
November 7, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29111272/novel-hbv-recombinants-between-genotypes-b-and-c-in-3-terminal-reverse-transcriptase-rt-sequences-are-associated-with-enhanced-viral-dna-load-higher-rt-point-mutation-rates-and-place-of-birth-among-chinese-patients
#17
Baoming Liu, Jing-Xian Yang, Ling Yan, Hui Zhuang, Tong Li
As one of the major global public health concerns, hepatitis B virus (HBV) can be divided into at least eight genotypes, which may be related to disease severity and treatment response. We previously demonstrated that genotypes B and C HBV, with distinct geographical distribution in China, had divergent genotype-dependent amino acid polymorphisms and variations in reverse transcriptase (RT) gene region, a target of antiviral therapy using nucleos(t)ide analogues. Recently recombination between HBV genotypes B and C was reported to occur in the RT region...
October 27, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29111235/genomic-stability-in-syndromic-basal-cell-carcinoma
#18
Audris Chiang, Prajakta D Jaju, Prag Batra, Melika Rezaee, Ervin H Epstein, Jean Y Tang, Kavita Y Sarin
Basal cell cancers (BCCs) are characterized by up-regulation of Hedgehog pathway through loss of Patched1 or activation of Smoothened, and smoothened-inhibitors such as vismodegib are effective therapies for advanced BCCs. Although most BCCs are sporadic, rare individuals with Basal Cell Nevus Syndrome (BCNS) harbor germline defects in Patched1 and develop up to hundreds of tumors that are histopathologically indistinguishable from sporadic BCCs. Interestingly, BCNS-BCCs are more responsive to Smoothened-inhibitors than sporadic BCCs, with minimal development of resistance...
October 27, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29110857/inter-relationship-between-pd-l1-expression-and-clinic-pathological-features-and-driver-gene-mutations-in-pulmonary-sarcomatoid-carcinomas
#19
Filippo Lococo, Federica Torricelli, Giulio Rossi, Marco Alifano, Diane Damotte, Cristian Rapicetta, Ione Tamagnini, Alberto Cavazza, Simonetta Piana, Carla Galeone, Massimiliano Paci, Alessia Ciarrocchi
INTRODUCTION: Pulmonary Sarcomatoid Carcinoma (PSC) is a rare subset of NSCLC, associated with worse prognosis and resistant to platinum-based regimens. Recent investigations have shown high levels of PD-L1 expression in PSC, providing a rationale for the potential use of immunotherapy. In this study, we investigated whether the PD-L1 expression was related to clinico-pathologic and molecular characteristics. MATERIALS AND METHODS: Fortythree surgically-resected PSCs were selected from 2006 to 2014 and clinical information retrieved...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29109227/the-impact-of-recombination-on-human-mutation-load-and-disease
#20
REVIEW
Isabel Alves, Armande Ang Houle, Julie G Hussin, Philip Awadalla
Recombination promotes genomic integrity among cells and tissues through double-strand break repair, and is critical for gamete formation and fertility through a strict regulation of the molecular mechanisms associated with proper chromosomal disjunction. In humans, congenital defects and recurrent structural abnormalities can be attributed to aberrant meiotic recombination. Moreover, mutations affecting genes involved in recombination pathways are directly linked to pathologies including infertility and cancer...
December 19, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
keyword
keyword
101882
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"