keyword
MENU ▼
Read by QxMD icon Read
search

Mutational load

keyword
https://www.readbyqxmd.com/read/27903797/accumulation-of-pol-mutations-selected-by-hla-b-52-01-c-12-02-protective-haplotype-restricted-ctls-causes-low-plasma-viral-load-due-to-low-viral-fitness-of-mutant-viruses
#1
Hayato Murakoshi, Madoka Koyanagi, Takayuki Chikata, Mohammad Arif Rahman, Nozomi Kuse, Keiko Sakai, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi
: HLA-B*52:01-C*12:02, which is the most abundant haplotype in Japan, has a protective effect on disease progression in HIV-1-infected Japanese individuals, whereas HLA-B*57 and -B*27 protective alleles are very rare in Japan. A previous study on HLA-associated polymorphisms demonstrated that the number of HLA-B*52:01-associated mutations at four Pol positions was inversely correlated with plasma viral load (pVL) in HLA-B*52:01-negative individuals, suggesting that the transmission of HIV-1 with these mutations could modulate the pVL in the population...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27903500/primary-resistance-to-pd-1-blockade-mediated-by-jak%C3%A2-mutations
#2
Daniel Sanghoon Shin, Jesse M Zaretsky, Helena Escuin-Ordinas, Angel Garcia-Diaz, Siwen Hu-Lieskovan, Anusha Kalbasi, Catherine S Grasso, Willy Hugo, Salemiz Sandoval, Davis Y Torrejon, Nicolaos Palaskas, Gabriel Abril Rodriguez, Giulia Parisi, Ariel Azhdam, Bartosz Chmielowski, Grace Cherry, Elizabeth Seja, Beata Berent-Maoz, I Peter Shintaku, Dung Thi Le, Drew M Pardoll, Luis A Diaz, Paul C Tumeh, Thomas G Graeber, Roger S Lo, Begoña Comin-Anduix, Antoni Ribas
Loss of function mutations in JAK½ can lead to acquired resistance to anti-programmed death protein 1 (PD-1) therapy. We reasoned they may also be involved in primary resistance to anti-PD-1 therapy. JAK½ inactivating mutations were noted in tumor biopsies of 1 of 23 patients with melanoma and in 1 of 16 patients with mismatch repair deficient colon cancer treated with PD-1 blockade. Both cases had a high mutational load but did not respond to anti-PD-1 therapy. Two out of 48 human melanoma cell lines had JAK½ mutations, which led to lack of PD-L1 expression upon interferon gamma exposure mediated by inability to signal through the interferon gamma receptor pathway...
November 30, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27902431/effects-of-chromosomal-deletion-of-the-operon-encoding-the-multiple-resistance-and-ph-mrp-antiporter-in-vibrio-cholerae
#3
Alisha Marie Aagesen, Carla B Schubiger, Eric C Hobson, Pavel Dibrov, Claudia Häse
To examine the possible physiological significance of Mrp, a multi-subunit cation-proton antiporter from Vibrio cholerae, a chromosomal deletion Δmrp of V. cholerae was constructed and characterized. The resulting mutant showed a consistent early growth defect in LB broth that became more evident at elevated pH of the growth medium and increasing Na+ or K+ loads. After 24 hours of incubation, these differences disappear likely due to the concerted effort of other cation pumps in the mrp mutant. Phenotype Microarray analyses revealed an unexpected systematic defect in nitrogen utilization in the Δmrp mutant that was complemented by using the mrpA'-F operon on an arabinose-inducible expression vector...
October 24, 2016: Microbiology
https://www.readbyqxmd.com/read/27902325/targeting-naturally-occurring-epitope-variants-of-hepatitis-c-virus-with-high-affinity-t-cell-receptors
#4
Huajun Zhang, Jianbing Zhang, Lei Chen, Zhiming Weng, Ye Tian, Haifeng Zhao, Youjia Li, Lin Chen, Zhaoduan Liang, Hongjun Zheng, Wenzhuo Zhao, Shi Zhong, Yi Li
Hepatitis C virus (HCV) readily establishes chronic infection, which is characterized by failure of virus-specific CD8+ T cells. HCV uses epitope mutation and T-cell exhaustion to escape from the host immune response. Previously, we engineered high-affinity T-cell receptors (HATs) targeting HIV escape mutants. In this study, the affinity of a T-cell receptor specific for the human leukocyte antigen (HLA)-A2-restricted HCV immunodominant epitope NS3 1406-1415 (KLVALGINAV) was improved from a KD of 6.6 µM to 40 pM...
November 11, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27901509/how-does-epistasis-influence-the-response-to-selection
#5
N H Barton
Much of quantitative genetics is based on the 'infinitesimal model', under which selection has a negligible effect on the genetic variance. This is typically justified by assuming a very large number of loci with additive effects. However, it applies even when genes interact, provided that the number of loci is large enough that selection on each of them is weak relative to random drift. In the long term, directional selection will change allele frequencies, but even then, the effects of epistasis on the ultimate change in trait mean due to selection may be modest...
November 30, 2016: Heredity
https://www.readbyqxmd.com/read/27900363/integration-of-genomics-and-histology-revises-diagnosis-and-enables-effective-therapy-of-refractory-cancer-of-unknown-primary-with-pdl1-amplification
#6
Stefan Gröschel, Martin Bommer, Barbara Hutter, Jan Budczies, David Bonekamp, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Christina Geörg, Daniela Richter, Nicole Pfarr, Katrin Pfütze, Stephan Wolf, Peter Schirmacher, Dirk Jäger, Christof von Kalle, Benedikt Brors, Hanno Glimm, Wilko Weichert, Albrecht Stenzinger, Stefan Fröhling
Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27897226/viral-and-host-characteristics-of-recent-and-established-hiv-1-infections-in-kisumu-based-on-a-multiassay-approach
#7
Newton Otecko, Seth Inzaule, Collins Odhiambo, George Otieno, Valarie Opollo, Alex Morwabe, Kennedy Were, Kenneth Ndiege, Fredrick Otieno, Andrea A Kim, Clement Zeh
Integrated approaches provide better understanding of HIV/AIDS epidemics. We optimised a multiassay algorithm (MAA) and assessed HIV incidence, correlates of recent infections, viral diversity, plus transmission clusters among participants screened for Kisumu Incidence Cohort Study (KICoS1) (2007-2009). We performed BED-CEIA, Limiting antigen (LAg) avidity, Biorad avidity, and viral load (VL) tests on HIV-positive samples. Genotypic analyses focused on HIV-1 pol gene. Correlates of testing recent by MAA were assessed using logistic regression model...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895760/prioritization-of-non-coding-disease-causing-variants-and-long-non-coding-rnas-in-liver-cancer
#8
Hua Li, Zekun He, Yang Gu, Lin Fang, Xin Lv
There are multiple bioinformatics tools available for the detection of coding driver mutations in cancers. However, the prioritization of pathogenic non-coding variants remains a challenging and demanding task. The present study was performed to discriminate non-coding disease-causing mutations and prioritize potential cancer-implicated long non-coding RNAs (lncRNAs) in liver cancer using a logistic regression model. A logistic regression model was constructed by combining 19,153 disease-associated ClinVar and human gene mutation database pathogenic variants as the response variable and non-coding features as the predictor variable...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27894351/characterizing-the-morbid-genome-of-ciliopathies
#9
Ranad Shaheen, Katarzyna Szymanska, Basudha Basu, Nisha Patel, Nour Ewida, Eissa Faqeih, Amal Al Hashem, Nada Derar, Hadeel Alsharif, Mohammed A Aldahmesh, Anas M Alazami, Mais Hashem, Niema Ibrahim, Firdous M Abdulwahab, Rawda Sonbul, Hisham Alkuraya, Maha Alnemer, Saeed Al Tala, Muneera Al-Husain, Heba Morsy, Mohammed Zain Seidahmed, Neama Meriki, Mohammed Al-Owain, Saad AlShahwan, Brahim Tabarki, Mustafa A Salih, Tariq Faquih, Mohamed El-Kalioby, Marius Ueffing, Karsten Boldt, Clare V Logan, David A Parry, Nada Al Tassan, Dorota Monies, Andre Megarbane, Mohamed Abouelhoda, Anason Halees, Colin A Johnson, Fowzan S Alkuraya
BACKGROUND: Ciliopathies are clinically diverse disorders of the primary cilium. Remarkable progress has been made in understanding the molecular basis of these genetically heterogeneous conditions; however, our knowledge of their morbid genome, pleiotropy, and variable expressivity remains incomplete. RESULTS: We applied genomic approaches on a large patient cohort of 371 affected individuals from 265 families, with phenotypes that span the entire ciliopathy spectrum...
November 28, 2016: Genome Biology
https://www.readbyqxmd.com/read/27892678/characterization-and-prognosis-significance-of-jak2-v617f-mpl-and-calr-mutations-in-philadelphia-negative-myeloproliferative-neoplasms
#10
Roongrudee Singdong, Teerapong Siriboonpiputtana, Takol Chareonsirisuthigul, Adcharee Kongruang, Nittaya Limsuwanachot, Tanasan Sirirat, Suporn Chuncharunee, Budsaba Rerkamnuaychoke
Background: The discovery of somatic acquired mutations of JAK2 (V617F) in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) has not only improved rational disease classification and prognostication but also brings new understanding insight into the pathogenesis of diseases. Dosage effects of the JAK2 (V617F) allelic burden in Ph-negative MPNs may partially influence clinical presentation, disease progression, and treatment outcome...
January 10, 2016: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/27890952/a-study-of-antiretroviral-resistance-patterns-in-treatment-experienced-and-naive-human-immunodeficiency-virus-infected-patients
#11
Raj Harjani, Ram Malkani
BACKGROUND: About 10% of the patients had surveillance drug-related mutations for nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in an Indian study. It was also reported that resistance was maximum for nucleoside reverse transcriptase inhibitors (NRTIs) and minimum for PIs. METHODS: The present study was a cross-sectional assessment of 21 human immunodeficiency virus (HIV)-infected individuals attending a HIV care center in a tertiary care center in Mumbai, Maharashtra, India...
July 2016: Indian Journal of Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/27890932/il-10-production-by-cll-cells-is-enhanced-in-the-anergic-ighv-mutated-subset-and-associates-with-reduced-dna-methylation-of-the-il10-locus
#12
S Drennan, A D'Avola, Y Gao, C Weigel, E Chrysostomou, A J Steele, T Zenz, C Plass, P W Johnson, A P Williams, G Packham, F K Stevenson, C C Oakes, F Forconi
Chronic lymphocytic leukemias (CLL) with unmutated (U-CLL) or mutated (M-CLL) IGHV have variable features of immunosuppression, possibly influenced by those CLL cells activated to produce IL-10. The two subsets differ in their levels of anergy, defined by low surface IgM levels/signaling capacity, and in their DNA methylation profile, particularly variable in M-CLL. We have now found that levels of IL-10 produced by activated CLL cells were highly variable. Levels were higher in M-CLL than in U-CLL and correlated with anergy...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27890785/genomic-characterization-of-dysplastic-nevi-unveils-implications-for-diagnosis-of-melanoma
#13
Rachel D Melamed, Iraz T Aydin, Geena Susan Rajan, Robert Phelps, David N Silvers, Kevin J Emmett, Georg Brunner, Raul Rabadan, Julide Tok Celebi
A well-defined risk factor and precursor for cutaneous melanoma is the dysplastic nevus. These benign tumors represent clonal hyperproliferation of melanocytes that are in a senescent-like state, but with occasional malignant transformation events. To portray the mutational repertoire of dysplastic nevi in patients with the dysplastic nevus syndrome, and to determine the discriminatory profiles of melanocytic nevi (including dysplastic nevi) from melanoma, we sequenced exomes of melanocytic nevi including dysplastic nevi (n = 19), followed by a targeted gene panel (785 genes) characterization of melanocytic nevi (n = 46) and primary melanomas (n = 42)...
November 24, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27888600/-darunavir-cobicistat-monotherapy-experience-in-a-tertiary-hospital
#14
L Yunquera-Romero, R Asensi-Díez, J C Del Rio-Valencia, I Muñoz-Castillo, M A Castaño-Carracedo
OBJECTIVE: Ritonavir-boosted protease inhibitor (IP/r) monotherapy: darunavir/ritonavir (DRV/r) or lopinavir/ritonavir (LPV/r) monotherapy is only provided in the major treatment guidelines in pretreated patients to prevent toxicity associated with nucleoside/nucleotide reverse transcriptase inhibitor (NRTI), reduce costs and simplify antiretroviral treatment. To start IP/r monotherapy, according to GESIDA guidelines 2016, patients need to meet the following criteria: absence of chronic hepatitis B, plasma viral load <50 copies/ mL for at least 6 months and absence of protease inhibitors mutations or previous virologic failures to IP/r...
December 2016: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/27888322/allee-effect-the-story-behind-the-stabilization-or-extinction-of-microbial-ecosystem
#15
REVIEW
Madhurankhi Goswami, Purnita Bhattacharyya, Prosun Tribedi
A population exhibiting Allee effect shows a positive correlation between population fitness and population size or density. Allee effect decides the extinction or conservation of a microbial population and thus appears to be an important criterion in population ecology. The underlying factor of Allee effect that decides the stabilization and extinction of a particular population density is the threshold or the critical density of their abundance. According to Allee, microbial populations exhibit a definite, critical or threshold density, beyond which the population fitness of a particular population increases with the rise in population density and below it, the population fitness goes down with the decrease in population density...
November 25, 2016: Archives of Microbiology
https://www.readbyqxmd.com/read/27887614/insight-into-k13-propeller-gene-polymorphism-and-ex-vivo-dha-response-profiles-from-cameroonian-isolates
#16
Sandie Menard, Joëlle Njila Tchoufack, Christelle Ngou Maffo, Sandrine E Nsango, Xavier Iriart, Luc Abate, Majoline Tchioffo Tsapi, Parfait H Awono-Ambéné, Francis A Abega Mekongo, Isabelle Morlais, Antoine Berry
BACKGROUND: The spread of Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia is a major source of concern and the emergence of resistance in Africa would have dramatic consequences, by increasing malaria mortality and morbidity. It is therefore urgent to implement regular monitoring in sentinel sites in sub-Saharan Africa using robust and easy-to-implement tools. The prevalence of k13-propeller mutations and the phenotypic profiles are poorly known in sub-Saharan Africa...
November 26, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27884957/altered-co2-sensitivity-of-connexin26-mutant-hemichannels-in%C3%A2-vitro
#17
Elizabeth de Wolf, Joseph van de Wiel, Jonathan Cook, Nicholas Dale
Connexin26 (Cx26) mutations underlie human pathologies ranging from hearing loss to keratitis ichthyosis deafness (KID) syndrome. Cx26 hemichannels are directly gated by CO2 and contribute to the chemosensory regulation of breathing. The KID syndrome mutation A88V is insensitive to CO2, and has a dominant negative action on the CO2 sensitivity of Cx26(WT) hemichannels, and reduces respiratory drive in humans. We have now examined the effect of further human mutations of Cx26 on its sensitivity to CO2 : Mutated Cx26 subunits, carrying one of A88S, N14K, N14Y, M34T, or V84L, were transiently expressed in HeLa cells...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27882070/serological-patterns-and-molecular-characterization-of-occult-hepatitis-b-virus-infection-among-blood-donors
#18
Hong Lin, Hong Zhao, Xinyi Tang, Wenjia Hu, Nizheng Jiang, Shaowen Zhu, Chengyin Huang
BACKGROUND: Hepatitis B infections, characterized by the presence of a viral genome without detectable hepatitis B surface antigen (HBsAg; Occult hepatitis B infection [OBI]), have been reported recently. OBJECTIVES: We performed serological and molecular characterization of OBI among blood donors at Jiangsu province blood center during years 2013 and 2014. METHODS: All donor samples were routinely screened by double enzyme-linked immunosorbent assay (ELISA) for hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), Treponema pallidum (TP), and alanine aminotransferase (ALT)...
October 2016: Hepatitis Monthly
https://www.readbyqxmd.com/read/27880854/increased-paternal-age-at-conception-is-associated-with-transcriptomic-changes-involved-in-mitochondrial-function-in-elderly-individuals
#19
Tapio Nevalainen, Laura Kananen, Saara Marttila, Juulia Jylhävä, Marja Jylhä, Antti Hervonen, Mikko Hurme
The increased paternal age at conception (PAC) has been associated with autism spectrum disorder (ASD), schizophrenia and other neurodevelopmental disorders, thus raising questions that imply, potential health concerns in the offspring. As opposed to female oogonia, the male germ cells undergo hundreds of cell divisions during the fertile years. Thus, the advanced paternal age is associated with increase of point mutations in the male spermatogonia DNA, implying that this could be the major driving mechanism behind the paternal age effect observed in the offspring...
2016: PloS One
https://www.readbyqxmd.com/read/27876397/efficacy-of-sodium-channel-blockers-in-scn2a-early-infantile-epileptic-encephalopathy
#20
Robertino Dilena, Pasquale Striano, Elena Gennaro, Laura Bassi, Sara Olivotto, Laura Tadini, Fabio Mosca, Sergio Barbieri, Federico Zara, Monica Fumagalli
BACKGROUND: Recent clinical evidence supports a targeted therapeutic approach for genetic epileptic encephalopathies based on the molecular dysfunction. PATIENT DESCRIPTION: A 2-day-old male infant presented with epileptic encephalopathy characterized by burst-suppression EEG background and tonic-clonic migrating partial seizures. The condition was refractory to phenobarbital, pyridoxine, pyridoxal phosphate and levetiracetam, but a dramatic response to an intravenous loading dose of phenytoin was documented by video-EEG monitoring...
November 19, 2016: Brain & Development
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"