keyword
MENU ▼
Read by QxMD icon Read
search

Mutational load

keyword
https://www.readbyqxmd.com/read/28439024/nip1-2-is-a-plasma-membrane-localized-transporter-mediating-aluminum-uptake-translocation-and-tolerance-in-arabidopsis
#1
Yuqi Wang, Ruihong Li, Demou Li, Xiaomin Jia, Dangwei Zhou, Jianyong Li, Sangbom M Lyi, Siyu Hou, Yulan Huang, Leon V Kochian, Jiping Liu
Members of the aquaporin (AQP) family have been suggested to transport aluminum (Al) in plants; however, the Al form transported by AQPs and the roles of AQPs in Al tolerance remain elusive. Here we report that NIP1;2, a plasma membrane-localized member of the Arabidopsis nodulin 26-like intrinsic protein (NIP) subfamily of the AQP family, facilitates Al-malate transport from the root cell wall into the root symplasm, with subsequent Al xylem loading and root-to-shoot translocation, which are critical steps in an internal Al tolerance mechanism in Arabidopsis We found that NIP1;2 transcripts are expressed mainly in the root tips, and that this expression is enhanced by Al but not by other metal stresses...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28439008/interaction-of-proliferating-cell-nuclear-antigen-with-pms2-is-required-for-mutl%C3%AE-activation-and-function-in-mismatch-repair
#2
Jochen Genschel, Lyudmila Y Kadyrova, Ravi R Iyer, Basanta K Dahal, Farid A Kadyrov, Paul Modrich
Eukaryotic MutLα (mammalian MLH1-PMS2 heterodimer; MLH1-PMS1 in yeast) functions in early steps of mismatch repair as a latent endonuclease that requires a mismatch, MutSα/β, and DNA-loaded proliferating cell nuclear antigen (PCNA) for activation. We show here that human PCNA and MutLα interact specifically but weakly in solution to form a complex of approximately 1:1 stoichiometry that depends on PCNA interaction with the C-terminal endonuclease domain of the MutLα PMS2 subunit. Amino acid substitution mutations within a PMS2 C-terminal (721)QRLIAP motif attenuate or abolish human MutLα interaction with PCNA, as well as PCNA-dependent activation of MutLα endonuclease, PCNA- and DNA-dependent activation of MutLα ATPase, and MutLα function in in vitro mismatch repair...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28434899/mechanisms-responsible-for-imipenem-resistance-among-pseudomonas-aeruginosa-clinical-isolates-exposed-to-imipenem-concentrations-within-the-mutant-selection-window
#3
Foula Vassilara, Irene Galani, Maria Souli, Konstantinos Papanikolaou, Helen Giamarellou, Antonios Papadopoulos
The aim of this study was to determine the propensities of imipenem to select for resistant Pseudomonas aeruginosa mutants by determining the mutant prevention concentrations (MPCs) for 9 unrelated clinical isolates and the accession of any relationship with mechanisms of resistance development. The MPC/MIC ratios ranged from 4 to 16. Detection of resistance mechanisms in the mutant derivatives of the nine isolates mainly revealed inactivating mutations in the gene coding for outer membrane protein OprD. Point mutations leading to premature stop codons or amino acid substitution S278P, ≥1bp deletion leading to frameshift mutations and interruption of the oprD by an insertion sequence, were observed...
April 12, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28434406/efavirenz-based-simplification-after-successful-early-lopinavir-boosted-ritonavir-based-therapy-in-hiv-infected-children-in-burkina-faso-and-c%C3%A3-te-d-ivoire-the-monod-anrs-12206-non-inferiority-randomised-trial
#4
Désiré Lucien Dahourou, Madeleine Amorissani-Folquet, Karen Malateste, Clarisse Amani-Bosse, Malik Coulibaly, Carole Seguin-Devaux, Thomas Toni, Rasmata Ouédraogo, Stéphane Blanche, Caroline Yonaba, François Eboua, Philippe Lepage, Divine Avit, Sylvie Ouédraogo, Philippe Van de Perre, Sylvie N'Gbeche, Angèle Kalmogho, Roger Salamon, Nicolas Meda, Marguerite Timité-Konan, Valériane Leroy
BACKGROUND: The 2016 World Health Organization guidelines recommend all children <3 years start antiretroviral therapy (ART) on protease inhibitor-based regimens. But lopinavir/ritonavir (LPV/r) syrup has many challenges in low-income countries, including limited availability, requires refrigeration, interactions with anti-tuberculous drugs, twice-daily dosing, poor palatability in young children, and higher cost than non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. Successfully initiating LPV/r-based ART in HIV-infected children aged <2 years raises operational challenges that could be simplified by switching to a protease inhibitor-sparing therapy based on efavirenz (EFV), although, to date, EFV is not recommended in children <3 years...
April 24, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28432811/yu-et%C3%A2-al-host-cell-mutants-resistant-to-cryptosporidium-parvum-characterization-of-host-cell-mutants-significantly-resistant-to-cryptosporidium-parvum-infection
#5
Xue Yu, Haili Zhang, Guan Zhu
Cryptosporidium parvum is a parasitic protist and a causative agent of mild to severe diarrheal diseases in humans and animals. Despite its globally recognized importance, knowledge on the mechanism of parasite invasion and molecular interactions between host cells and the parasite is limited. Here we report the establishment of 43 mutant cell lines derived from HCT-8 cells by UV-induced mutagenesis and the characterization of three mutants with significantly reduced susceptibility to cryptosporidial infection...
April 22, 2017: Journal of Eukaryotic Microbiology
https://www.readbyqxmd.com/read/28428277/immune-gene-expression-is-associated-with-genomic-aberrations-in-breast-cancer
#6
Anton Safonov, Tingting Jiang, Giampaolo Bianchini, Balázs Győrffy, Thomas Karn, Christos Hatzis, Lajos Pusztai
The presence of tumor-infiltrating lymphocytes (TIL) is a favorable prognostic factor in breast cancer, but what drives immune infiltration remains unknown. Here we examine if clonal heterogeneity, total mutation load, neoantigen load, copy number variations (CNV), gene- or pathway-level somatic mutations, or germline polymorphisms (SNP) are associated with immune metagene expression in breast cancer subtypes. Thirteen published immune metagenes correlated separately with genomic metrics in the 3 major breast cancer subtypes...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427233/assessment-of-the-interlaboratory-variability-and-robustness-of-jak2v617f-mutation-assays-a-study-involving-a-consortium-of-19-italian-laboratories
#7
Margherita Perricone, Francesca Palandri, Emanuela Ottaviani, Mario Angelini, Laura Bagli, Enrica Bellesia, Meris Donati, Donato Gemmati, Patrizia Zucchini, Stefania Mancini, Valentina Marchica, Serena Trubini, Giovanna De Matteis, Silvia Di Zacomo, Mosè Favarato, Annamaria Fioroni, Caterina Bolzonella, Giorgia Maccari, Filippo Navaglia, Daniela Gatti, Luisa Toffolatti, Linda Orlandi, Vèronique Laloux, Marco Manfrini, Piero Galieni, Barbara Giannini, Alessia Tieghi, Sara Barulli, Maria Luisa Serino, Monica Maccaferri, Anna Rita Scortechini, Nicola Giuliani, Daniele Vallisa, Massimiliano Bonifacio, Patrizia Accorsi, Cristina Salbe, Vinicio Fazio, Milena Gusella, Eleonora Toffoletti, Marzia Salvucci, Mirija Svaldi, Filippo Gherlinzoni, Francesca Cassavia, Francesco Orsini, Giovanni Martinelli
To date, a plenty of techniques for the detection of JAK2V617F is used over different laboratories, with substantial differences in specificity and sensitivity. Therefore, to provide reliable and comparable results, the standardization of molecular techniques is mandatory.A network of 19 centers was established to 1) evaluate the inter- and intra-laboratory variability in JAK2V617F quantification, 2) identify the most robust assay for the standardization of the molecular test and 3) allow consistent interpretation of individual patient analysis results...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426285/the-yin-and-yang-of-autism-genetics-how-rare-de-novo-and-common-variations-affect-liability
#8
Pauline Chaste, Kathryn Roeder, Bernie Devlin
The etiology of autism spectrum disorder (ASD) is complex, involving both genetic and environmental contributions to individual and population-level liability. Early researchers hypothesized that ASD arises from polygenic inheritance, but later results, such as the identification of mutations in certain genes that are responsible for syndromes associated with ASD, led others to propose that de novo mutations of major effect would account for most cases. This yin and yang of monogenic causes and polygenic inheritance continues to this day...
April 19, 2017: Annual Review of Genomics and Human Genetics
https://www.readbyqxmd.com/read/28422757/cross-reactive-dengue-human-monoclonal-antibody-prevents-severe-pathologies-and-death-from-zika-virus-infections
#9
Yiu-Wing Kam, Cheryl Yi-Pin Lee, Teck-Hui Teo, Shanshan W Howland, Siti Naqiah Amrun, Fok-Moon Lum, Peter See, Nicholas Qing-Rong Kng, Roland G Huber, Mei-Hui Xu, Heng-Liang Tan, Andre Choo, Sebastian Maurer-Stroh, Florent Ginhoux, Katja Fink, Cheng-I Wang, Lisa F P Ng, Laurent Rénia
Zika virus (ZIKV) infections have been linked with neurological complications and congenital Zika syndrome. Given the high level of homology between ZIKV and the related flavivirus dengue virus (DENV), we investigated the level of cross-reactivity with ZIKV using a panel of DENV human mAbs. A majority of the mAbs showed binding to ZIKV virions, with several exhibiting neutralizing capacities against ZIKV in vitro. Three of the best ZIKV-neutralizing mAbs were found to recognize diverse epitopes on the envelope (E) glycoprotein: the highly conserved fusion-loop peptide, a conformation-specific epitope on the E monomer, and a quaternary epitope on the virion surface...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28422742/multi-omics-study-revealing-the-complexity-and-spatial-heterogeneity-of-tumor-infiltrating-lymphocytes-in-primary-liver-carcinoma
#10
Lijun Shi, Yang Zhang, Lin Feng, Liming Wang, Weiqi Rong, Fan Wu, Jianxiong Wu, Kaitai Zhang, Shujun Cheng
Intratumoral heterogeneity has been revealed in primary liver carcinoma (PLC). However, spatial heterogeneity of tumor-infiltrating lymphocytes (TILs), which reflects one dimension of a tumor's spatial heterogeneity, and the relationship between TIL diversity, local immune response and mutation burden remain unexplored in PLC. Therefore, we performed immune repertoire sequencing, gene expression profiling analysis and whole-exome sequencing in parallel on five regions of each tumor and on matched adjacent normal tissues and peripheral blood from five PLC patients...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420387/effects-of-host-restriction-factors-and-the-htlv-1-subtype-on-susceptibility-to-htlv-1-associated-myelopathy-tropical-spastic-paraparesis
#11
Satoshi Nozuma, Eiji Matsuura, Daisuke Kodama, Yuichi Tashiro, Toshio Matsuzaki, Ryuji Kubota, Shuji Izumo, Hiroshi Takashima
BACKGROUND: Although human T-lymphotropic virus type 1 (HTLV-1) infection is a prerequisite for the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), specific provirus mutations in HAM/TSP have not yet been reported. In this study, we examined whether HAM/TSP patients had the disease-specific genomic variants of HTLV-1 by analyzing entire sequences of HTLV-1 proviruses in these patients, including familial cases. In addition, we investigated the genetic variants of host restriction factors conferring antiretroviral activity to determine which mutations may be related to resistance or susceptibility to HAM/TSP...
April 19, 2017: Retrovirology
https://www.readbyqxmd.com/read/28418062/flexible-aspartates-propel-iron-to-the-ferroxidation-sites-along-pathways-stabilized-by-a-conserved-arginine-in-dps-proteins-from-mycobacterium-smegmatis
#12
Sunanda Margrett Williams, Dipankar Chatterji
DNA-binding proteins under starvation (Dps) are dodecameric nano-compartments for iron oxidation and storage in bacterial cells. These proteins have roughly spherical structures with a hollow interior where iron is stored. Through mutational analysis of a conserved arginine residue in the second Dps protein from Mycobacterium smegmatis, we have identified residues which stabilize the interfaces between the iron entry and ferroxidation sites. Also, we have used X-ray crystallography to determine the structures of co-crystals of iron and Dps in varying proportions and compare the changes in these ligand-bound forms with respect to the apo-protein...
April 18, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28416714/jinglebells-a-repository-of-immune-related-single-cell-rna-sequencing-datasets
#13
Hadas Ner-Gaon, Ariel Melchior, Nili Golan, Yael Ben-Haim, Tal Shay
Recent advances in single-cell RNA-sequencing (scRNA-seq) technology increase the understanding of immune differentiation and activation processes, as well as the heterogeneity of immune cell types. Although the number of available immune-related scRNA-seq datasets increases rapidly, their large size and various formats render them hard for the wider immunology community to use, and read-level data are practically inaccessible to the non-computational immunologist. To facilitate datasets reuse, we created the JingleBells repository for immune-related scRNA-seq datasets ready for analysis and visualization of reads at the single-cell level (http://jinglebells...
May 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28414306/targeting-prohibitins-with-chemical-ligands-inhibits-kras-mediated-lung-tumours
#14
H Yurugi, F Marini, C Weber, K David, Q Zhao, H Binder, L Désaubry, K Rajalingam
KRAS is one of the most frequently mutated oncogenes in human non-small cell lung cancers (NSCLCs). RAS proteins trigger multiple effector signalling pathways including the highly conserved RAF-MAPK pathway. CRAF, a direct RAS effector protein, is required for KRAS-mediated tumourigenesis. Thus, the molecular mechanisms driving the activation of CRAF are intensively studied. Prohibitin 1 (PHB1) is an evolutionarily conserved adaptor protein and interaction of CRAF with PHB1 at the plasma membrane is essential for CRAF activation...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28412158/lidocaine-attenuation-testing-an-in-vivo-investigation-of-putative-lqt3-associated-variants-in-the-scn5a-encoded-sodium-channel
#15
M D Heather N Anderson, J Martijn Bos, Jamie D Kapplinger, Jana M Meskill, Dan Ye, Michael J Ackerman
BACKGROUND: Long QT type 3 (LQT3) accounts for 5-10% of LQTS and results from gain-of-function mutations in the SCN5A-encoded sodium channel. Nearly 2% of healthy individuals host rare SCN5A variants of uncertain significance (VUS). Distinction of true LQT3-causative mutations from background genetic noise is essential. OBJECTIVE: This study was designed to assess the utility of the lidocaine attenuation test (LAT) in evaluating patients with possible LQT3. METHODS: We reviewed LAT results and medical records for 25 patients with a possible LQT3-associated SCN5A variant...
April 12, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28410019/mating-system-evolution-under-strong-pollen-limitation-evidence-of-disruptive-selection-through-male-and-female-fitness-in-clarkia-xantiana
#16
Ryan D Briscoe Runquist, Monica A Geber, Michael Pickett-Leonard, David A Moeller
Selection on floral traits in hermaphroditic plants is determined by both male and female reproductive success. However, predictions regarding floral trait and mating system evolution are often based solely on female fitness. Selection via male fitness has the potential to affect the outcomes of floral evolution. In this study, we used paternity analysis to assess individual selfing rates and selection on floral traits via male and female fitness in an experimental population of Clarkia xantiana where pollen limitation of seed set was strong...
May 2017: American Naturalist
https://www.readbyqxmd.com/read/28408790/hbv-viral-load-and-liver-enzyme-levels-may-be-associated-with-the-wild-mbl2-aa-genotype
#17
Tuane Carolina Ferreira Moura, Ednelza da Silva Graça Amoras, Mauro Sérgio Araújo, Maria Alice Freitas Queiroz, Simone Regina Souza da Silva Conde, Sâmia Demachki, Rosimar Neris Martins-Feitosa, Luiz Fernando Almeida Machado, Izaura Maria Vieira Cayres-Vallinoto, Ricardo Ishak, Antonio Carlos Rosário Vallinoto
The present study investigated the frequencies of rs1800450 (MBL (⁎)B, G>A), rs1800451 (MBL (⁎)C, G>A), and rs5030737 (MBL (⁎)D, C>T) polymorphisms in exon 1 of the MBL2 gene among patients with chronic viral hepatitis. Blood samples from patients infected with hepatitis B virus (HBV; n = 65), hepatitis C virus (HCV; n = 92), and a noninfected control group (n = 300) were investigated. The presence of polymorphisms was detected using a real-time polymerase chain reaction to correlate with liver disease pathogenesis and fibrosis staging according to the Metavir classification...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28406212/human-knockouts-and-phenotypic-analysis-in-a-cohort-with-a-high-rate-of-consanguinity
#18
Danish Saleheen, Pradeep Natarajan, Irina M Armean, Wei Zhao, Asif Rasheed, Sumeet A Khetarpal, Hong-Hee Won, Konrad J Karczewski, Anne H O'Donnell-Luria, Kaitlin E Samocha, Benjamin Weisburd, Namrata Gupta, Mozzam Zaidi, Maria Samuel, Atif Imran, Shahid Abbas, Faisal Majeed, Madiha Ishaq, Saba Akhtar, Kevin Trindade, Megan Mucksavage, Nadeem Qamar, Khan Shah Zaman, Zia Yaqoob, Tahir Saghir, Syed Nadeem Hasan Rizvi, Anis Memon, Nadeem Hayyat Mallick, Mohammad Ishaq, Syed Zahed Rasheed, Fazal-Ur-Rehman Memon, Khalid Mahmood, Naveeduddin Ahmed, Ron Do, Ronald M Krauss, Daniel G MacArthur, Stacey Gabriel, Eric S Lander, Mark J Daly, Philippe Frossard, John Danesh, Daniel J Rader, Sekar Kathiresan
A major goal of biomedicine is to understand the function of every gene in the human genome. Loss-of-function mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such 'human knockouts' can provide insight into gene function. Consanguineous unions are more likely to result in offspring carrying homozygous loss-of-function mutations. In Pakistan, consanguinity rates are notably high. Here we sequence the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), designed to understand the determinants of cardiometabolic diseases in individuals from South Asia...
April 12, 2017: Nature
https://www.readbyqxmd.com/read/28405516/assessment-of-tumor-infiltrating-tcrv%C3%AE-9v%C3%AE-2-%C3%AE-%C3%AE-lymphocyte-abundance-by-deconvolution-of-human-cancers-microarrays
#19
Marie Tosolini, Frédéric Pont, Mary Poupot, François Vergez, Marie-Laure Nicolau-Travers, David Vermijlen, Jean-Emmanuel Sarry, Francesco Dieli, Jean-Jacques Fournié
Most human blood γδ cells are cytolytic TCRVγ9Vδ2(+) lymphocytes with antitumor activity. They are currently investigated in several clinical trials of cancer immunotherapy but so far, their tumor infiltration has not been systematically explored across human cancers. Novel algorithms allowing the deconvolution of bulk tumor transcriptomes to find the relative proportions of infiltrating leucocytes, such as CIBERSORT, should be appropriate for this aim but in practice they fail to accurately recognize γδ T lymphocytes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28405504/pd-l1-cd274-copy-number-gain-expression-and-immune-cell-infiltration-as-candidate-predictors-for-response-to-immune-checkpoint-inhibitors-in-soft-tissue-sarcoma
#20
Jan Budczies, Gunhild Mechtersheimer, Carsten Denkert, Frederick Klauschen, Sadaf S Mughal, Priya Chudasama, Michael Bockmayr, Korinna Jöhrens, Volker Endris, Amelie Lier, Felix Lasitschka, Roland Penzel, Manfred Dietel, Benedikt Brors, Stefan Gröschel, Hanno Glimm, Peter Schirmacher, Marcus Renner, Stefan Fröhling, Albrecht Stenzinger
Soft-tissue sarcomas (STS) are rare malignancies that account for 1% of adult cancers and comprise more than 50 entities. Current therapeutic options for advanced-stage STS are limited. Immune checkpoint inhibitors targeting the PD-1/PD-L1 signaling axis are being explored as new treatment modality in STS; however, the determinants of response to these agents are largely unknown. Using the sarcoma data set of The Cancer Genome Altas (TCGA) and an independent cohort of untreated high-grade STS, we analyzed DNA copy number status and mRNA expression of PD-L1 in a total of 335 STS cases...
2017: Oncoimmunology
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"