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https://www.readbyqxmd.com/read/27912062/atomic-structure-of-the-cystic-fibrosis-transmembrane-conductance-regulator
#1
Zhe Zhang, Jue Chen
The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel evolved from the ATP-binding cassette (ABC) transporter family. In this study, we determined the structure of zebrafish CFTR in the absence of ATP by electron cryo-microscopy to 3.7 Å resolution. Human and zebrafish CFTR share 55% sequence identity, and 42 of the 46 cystic-fibrosis-causing missense mutational sites are identical. In CFTR, we observe a large anion conduction pathway lined by numerous positively charged residues...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27907212/diffuse-large-b-cell-lymphoma-cell-line-u-2946-model-for-mcl1-inhibitor-testing
#2
Hilmar Quentmeier, Hans G Drexler, Vivien Hauer, Roderick A F MacLeod, Claudia Pommerenke, Cord C Uphoff, Margarete Zaborski, Mattias Berglund, Gunilla Enblad, Rose-Marie Amini
Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma worldwide. We describe the establishment and molecular characteristics of the DLBCL cell line U-2946. This cell line was derived from a 52-year-old male with DLBCL. U-2946 cells carried the chromosomal translocation t(8;14) and strongly expressed MYC, but not the mature B-cell lymphoma associated oncogenes BCL2 and BCL6. Instead, U-2946 cells expressed the antiapoptotic BCL2 family member MCL1 which was highly amplified genomically (14n)...
2016: PloS One
https://www.readbyqxmd.com/read/27906699/reversal-effects-of-local-anesthetics-on-p-glycoprotein-mediated-cancer-multidrug-resistance
#3
Yong Hu, Xiaobing Qin, Haixia Cao, Shaorong Yu, Jifeng Feng
The existence of multidrug resistance (MDR) is the main reason for failure in cancer chemotherapy. The main mechanism of MDR is the overexpression of P-glycoprotein (P-gp). P-gp, a 170 kDa transmembrane phosphorylated glycoprotein encoded by ABCB1 belonging to a member of the ATP-binding cassette (ABC) super-family of the membrane transporters, is also known as the MDR protein. Local anesthetics (LAs) are a major contributor to medical practice. As a cornerstone of analgesia, LAs provides myriad benefits...
November 30, 2016: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27902408/sequencing-rare-marine-actinomycete-genomes-reveals-high-density-of-unique-natural-product-biosynthetic-gene-clusters
#4
Michelle Antoinette Schorn, Mohammad M Alanjary, Kristen Aguinaldo, Anton Korobeynikov, Sheila Podell, Nastassia V Patin, Tommie Lincecum, Paul R Jensen, Nadine Ziemert, Bradley S Moore
Traditional natural product discovery methods have nearly exhausted the accessible diversity of microbial chemicals, making new sources and techniques paramount in the search for new molecules. Marine actinomycete bacteria have recently come into the spotlight as fruitful producers of structurally diverse secondary metabolites, and remain relatively untapped. In this study we sequenced twenty-one marine-derived actinomycete strains, rarely studied for their secondary metabolite potential and underrepresented in current genomic databases...
October 27, 2016: Microbiology
https://www.readbyqxmd.com/read/27901114/genome-wide-diversity-and-association-mapping-for-capsaicinoids-and-fruit-weight-in-capsicum-annuum-l
#5
Padma Nimmakayala, Venkata L Abburi, Thangasamy Saminathan, Suresh B Alaparthi, Aldo Almeida, Brittany Davenport, Marjan Nadimi, Joshua Davidson, Krittika Tonapi, Lav Yadav, Sridhar Malkaram, Gopinath Vajja, Gerald Hankins, Robert Harris, Minkyu Park, Doil Choi, John Stommel, Umesh K Reddy
Accumulated capsaicinoid content and increased fruit size are traits resulting from Capsicum annuum domestication. In this study, we used a diverse collection of C. annuum to generate 66,960 SNPs using genotyping by sequencing. The study identified 1189 haplotypes containing 3413 SNPs. Length of individual linkage disequilibrium (LD) blocks varied along chromosomes, with regions of high and low LD interspersed with an average LD of 139 kb. Principal component analysis (PCA), Bayesian model based population structure analysis and an Euclidean tree built based on identity by state (IBS) indices revealed that the clustering pattern of diverse accessions are in agreement with capsaicin content (CA) and fruit weight (FW) classifications indicating the importance of these traits in shaping modern pepper genome...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27886333/association-between-the-polymorphisms-in-the-atp-binding-cassette-genes-abcb1-and-abcc2-and-the-risk-of-drug-resistant-epilepsy-in-a-chinese-han-population
#6
T Xue, Z N Lu
Epilepsy is a common disease of the nervous system; approximately 20-30% of all patients with epilepsy are reported resistant to antiepileptic drugs. ABCB1 and ABCC2 are members of ATP-binding cassette transporter (ABC) family that is involved in the excretion of antiepileptic drugs. In this case-control study, we have investigated the role of ABCB1 rs1045642 and rs2032582 and ABCC2 rs2273697 and rs717620 single nucleotide polymorphisms in antiepileptic drug-resistance in patients with epilepsy. A total of 254 patients with epilepsy (104 drug-resistant and 150 drug-responsive) were recruited from the People's Hospital of Wuhan University between March 2013 and April 2014...
November 25, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27859397/global-transcriptomic-response-of-anoxybacillus-sp-sk-3-4-to-aluminum-exposure
#7
Jia Chun Lim, Suganthi Thevarajoo, Chitra Selvaratnam, Kian Mau Goh, Mohd Shahir Shamsir, Zaharah Ibrahim, Chun Shiong Chong
Anoxybacillus sp. SK 3-4 is a Gram-positive, rod-shaped bacterium and a member of family Bacillaceae. We had previously reported that the strain is an aluminum resistant thermophilic bacterium. This is the first report to provide a detailed analysis of the global transcriptional response of Anoxybacillus when the cells were exposed to 600 mg L(-1) of aluminum. The transcriptome was sequenced using Illumina MiSeq sequencer. Total of 708 genes were differentially expressed (fold change >2.00) with 316 genes were up-regulated while 347 genes were down-regulated, in comparing to control with no aluminum added in the culture...
November 17, 2016: Journal of Basic Microbiology
https://www.readbyqxmd.com/read/27835832/genome-wide-identification-of-atp-binding-cassette-abc-transporters-and-conservation-of-their-xenobiotic-transporter-function-in-the-monogonont-rotifer-brachionus-koreanus
#8
Chang-Bum Jeong, Hui-Su Kim, Hye-Min Kang, Young Hwan Lee, Bingsheng Zhou, Joonho Choe, Jae-Seong Lee
The ATP-binding cassette (ABC) transporter family is one of the largest gene family in animals, and members of this family are known to be involved in various biological processes due to their ability to transport a wide range of substrates across membranes using ATP cleavage-derived energy. We identified 61 ABC transporters in the genome of the monogonont rotifer Brachionus koreanus, and classified these into eight distinct subfamilies (A-H) by phylogenetic analysis. ABC transporters in the rotifer B. koreanus are comprised of 11 ABCA genes, 19 ABCB genes, 14 ABCC genes, 3 ABCD genes, 1 ABCE gene, 3 ABCF genes, 8 ABCG genes, and 2 ABCH genes...
October 24, 2016: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/27825775/analysis-of-gene-gain-and-loss-in-the-evolution-of-predatory-bacteria
#9
Nan Li, Kai Wang, Henry N Williams, Jun Sun, Changling Ding, Xiaoyun Leng, Ke Dong
Predatory bacteria are ubiquitously distributed in nature in including in aquatic environments, sewage, intestinal tracts of animals and humans, rhizophere and, soils. However, our understanding of their evolutionary history is limited. Results of recent studies have shown that acquiring novel genes is a major force driving bacterial evolution. Therefore, to gain a better understanding of the impact of gene gain and loss in the evolution of bacterial predators, this study employed comparative genomic approaches to identify core-set gene families and species-specific gene families, and model gene gain and loss events among 11 genomes that represented diverse lineages...
November 5, 2016: Gene
https://www.readbyqxmd.com/read/27821447/synthetic-organotellurium-compounds-sensitize-drug-resistant-candida-albicans-clinical-isolates-to-fluconazole
#10
L F Reis de Sá, F T Toledo, A C Gonçalves, B A Sousa, A A Dos Santos, P F Brasil, V A Duarte da Silva, A C Tessis, J A Ramos, M A Carvalho, E Lamping, A Ferreira-Pereira
Invasive Candida albicans infections are a serious health threat for immunocompromised individuals. Fluconazole is most commonly used to treat these infections, but resistance due to the overexpression of multidrug efflux pumps is of grave concern. This study evaluated the ability of five synthetic organotellurium compounds to reverse fluconazole resistance of C. albicans clinical isolates. Compounds 1-4, at < 10 μg/ml, ameliorated fluconazole resistance of Saccharomyces cerevisiae strains overexpressing the major C...
November 7, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27798401/fundamentals-and-recent-developments-in-approximate-bayesian-computation
#11
Jarno Lintusaari, Michael U Gutmann, Ritabrata Dutta, Samuel Kaski, Jukka Corander
Bayesian inference plays an important role in phylogenetics, evolutionary biology, and in many other branches of science. It provides a principled framework for dealing with uncertainty and quantifying how it changes in the light of new evidence. For many complex models and inference problems, however, only approximate quantitative answers are obtainable. Approximate Bayesian computation (ABC) refers to a family of algorithms for approximate inference that makes a minimal set of assumptions by only requiring that sampling from a model is possible...
October 19, 2016: Systematic Biology
https://www.readbyqxmd.com/read/27794466/engineering-of-an-lrp-family-regulator-sace_lrp-improves-erythromycin-production-in-saccharopolyspora-erythraea
#12
Jing Liu, Yunfu Chen, Weiwei Wang, Min Ren, Panpan Wu, Yansheng Wang, Changrun Li, Lixin Zhang, Hang Wu, David T Weaver, Buchang Zhang
Leucine-responsive regulatory proteins (Lrps) are a group of transcriptional regulators that regulate diverse cellular processes in bacteria and archaea. However, the regulatory role of Lrps in antibiotic biosynthesis remains poorly understood. In this study, we show that SACE_5388, an Lrp family regulator named as SACE_Lrp, is an efficient regulator for transporting and catabolizing branched-chain amino acids (BCAAs), playing an important role in regulating erythromycin production in Saccharopolyspora erythraea...
October 26, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27779650/hoxb4-knockdown-reverses-multidrug-resistance-of-human-myelogenous-leukemia-k562-adm-cells-by-downregulating-p-gp-mrp1-and-bcrp-expression-via-pi3k-akt-signaling-pathway
#13
Hong Wang, Xiu-Hong Jia, Jie-Ru Chen, Ying-Jie Yi, Jian-Yong Wang, You-Jie Li, Shu-Yang Xie
Multidrug resistance (MDR) plays a pivotal role in human chronic myelogenous leukemia (CML) chemotherapy failure. MDR is mainly associated with the overexpression of drug efflux transporters of the ATP-binding cassette (ABC) proteins. Phosphoinositide 3-kinase (PI3K)/Akt signaling cascade is involved in the MDR phenotype and is correlated with multidrug resistance 1 (MDR1)/P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) expression in many human malignancies...
October 18, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27766264/abc-transporter-subfamily-d-distinct-differences-in-behavior-between-abcd1-3-and-abcd4-in-subcellular-localization-function-and-human-disease
#14
Kosuke Kawaguchi, Masashi Morita
ATP-binding cassette (ABC) transporters are one of the largest families of membrane-bound proteins and transport a wide variety of substrates across both extra- and intracellular membranes. They play a critical role in maintaining cellular homeostasis. To date, four ABC transporters belonging to subfamily D have been identified. ABCD1-3 and ABCD4 are localized to peroxisomes and lysosomes, respectively. ABCD1 and ABCD2 are involved in the transport of long and very long chain fatty acids (VLCFA) or their CoA-derivatives into peroxisomes with different substrate specificities, while ABCD3 is involved in the transport of branched chain acyl-CoA into peroxisomes...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27760172/inhibition-of-snail-family-transcriptional-repressor-2-snai2-enhances-multidrug-resistance-of-hepatocellular-carcinoma-cells
#15
Xin-Yu Zhao, Lei Li, Xiao-Bo Wang, Rong-Jie Fu, Ya-Ping Lv, Wei Jin, Chao Meng, Guo-Qiang Chen, Lei Huang, Ke-Wen Zhao
China accounts for almost half of the total number of liver cancer cases and deaths worldwide, and hepatocellular carcinoma (HCC) is the most primary liver cancer. Snail family transcriptional repressor 2 (SNAI2) is known as an epithelial to mesenchymal transition-inducing transcription factor that drives neoplastic epithelial cells into mesenchymal phenotype. However, the roles of endogenous SNAI2 remain controversial in different types of malignant tumors. Herein, we surprisingly identify that anchorage-independent growth, including the formation of tumor sphere and soft agar colony, is significantly increased when SNAI2 expression is inhibited by shRNAs in HCC cells...
2016: PloS One
https://www.readbyqxmd.com/read/27752851/improving-production-of-protease-from-pseudoalteromonas-sp-csn423-by-random-mutagenesis
#16
Cuiling Wu, Dan Liu, Xinghao Yang, Ribang Wu, Jiang Zhang, Jiafeng Huang, Hailun He
Pseudoalteromonas sp. CSN423, a marine strain, can express a major protease designated as E423 and it was secreted into the supernatant. To improve the protease E423 yield, Pseudoalteromonas sp. CSN423 was subjected to mutagenesis using UV irradiation. Mutant strain with 5.1-fold higher protease yield was isolated and named as Pseudoalteromonas sp. CSN423-M. Three protease bands were detected by zymography with casein as substrate, and results of mass spectrometry (MS) showed that two lower molecular weight protein bands were the same protease but with different mature forms...
October 17, 2016: Marine Biotechnology
https://www.readbyqxmd.com/read/27748968/bacillus-subtilis-mntr-coordinates-the-transcriptional-regulation-of-manganese-uptake-and-efflux-systems
#17
Xiaojuan Huang, Jung-Ho Shin, Azul Pinochet-Barros, Tina T Su, John D Helmann
The Bacillus subtilis MntR metalloregulatory protein senses manganese, an essential element required for central metabolism, oxidative stress resistance and replication. An mntR null mutant is highly sensitive to Mn(II) intoxication, which is attributed in part to the constitutive expression of two importers: the proton-dependent NRAMP family transporter MntH and the ABC transporter MntABCD. Here, we show that an mntR null mutant is still sensitive to Mn(II) intoxication even if both of the import systems are absent...
October 17, 2016: Molecular Microbiology
https://www.readbyqxmd.com/read/27734094/the-cystic-fibrosis-transmembrane-conductance-regulator-cftr-and-its-stability
#18
Xin Meng, Jack Clews, Vasileios Kargas, Xiaomeng Wang, Robert C Ford
The cystic fibrosis transmembrane conductance regulator (CFTR) is responsible for the disease cystic fibrosis (CF). It is a membrane protein belonging to the ABC transporter family functioning as a chloride/anion channel in epithelial cells around the body. There are over 1500 mutations that have been characterised as CF-causing; the most common of these, accounting for ~70 % of CF cases, is the deletion of a phenylalanine at position 508. This leads to instability of the nascent protein and the modified structure is recognised and then degraded by the ER quality control mechanism...
October 12, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27718219/molecular-heterogeneity-of-aggrecan-based-perineuronal-nets-around-five-subclasses-of-parvalbumin-expressing-neurons-in-the-mouse-hippocampus
#19
Jun Yamada, Shozo Jinno
Subsets of GABAergic neurons are surrounded by perineuronal nets (PNNs), which play a critical role in the regulation of neural plasticity and neuroprotection. Although the plant lectin Wisteria floribunda agglutinin (WFA) has been commonly used to label PNNs, WFA only detects N-acetyl-d-galactosamine on aggrecan, a member of the lectican family. In this study, we used WFA and the antibody against the core protein of aggrecan (ACAN) to investigate the molecular heterogeneity of aggrecan-based PNNs around five subclasses of parvalbumin-expressing (PV+) γ-aminobutyric acid (GABA)ergic neurons in the CA1 and CA3 regions of the mouse hippocampus...
October 7, 2016: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/27708121/harmonization-of-food-frequency-questionnaires-and-dietary-pattern-analysis-in-4-ethnically-diverse-birth-cohorts
#20
Russell J de Souza, Michael A Zulyniak, Dipika Desai, Mateen R Shaikh, Natalie C Campbell, Diana L Lefebvre, Milan Gupta, Julie Wilson, Gita Wahi, Stephanie A Atkinson, Koon K Teo, Padmaja Subbarao, Allan B Becker, Piushkumar J Mandhane, Stuart E Turvey, Malcolm R Sears, Sonia S Anand
BACKGROUND: Canada is an ethnically diverse nation, which introduces challenges for health care providers tasked with providing evidence-based dietary advice. OBJECTIVES: We aimed to harmonize food-frequency questionnaires (FFQs) across 4 birth cohorts of ethnically diverse pregnant women to derive robust dietary patterns to investigate maternal and newborn outcomes. METHODS: The NutriGen Alliance comprises 4 prospective birth cohorts and includes 4880 Canadian mother-infant pairs of predominantly white European [CHILD (Canadian Healthy Infant Longitudinal Development) and FAMILY (Family Atherosclerosis Monitoring In earLY life)], South Asian [START (SouTh Asian birth cohoRT)-Canada], or Aboriginal [ABC (Aboriginal Birth Cohort)] origins...
November 2016: Journal of Nutrition
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