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https://www.readbyqxmd.com/read/28642445/identification-of-a-cytogenetic-and-molecular-subgroup-of-acute-myeloid-leukemias-showing-sensitivity-to-l-asparaginase
#1
Salvatore Nicola Bertuccio, Salvatore Serravalle, Annalisa Astolfi, Annalisa Lonetti, Valentina Indio, Anna Leszl, Andrea Pession, Fraia Melchionda
L-Asparaginase (L-Asp) is an enzyme that catalyzes the hydrolysis of L-asparagine to L-aspartic acid, and its depletion induces leukemic cell death. L-Asp is an important component of treatment regimens for Acute Lymphoblastic Leukemia (ALL). Sensitivity to L-Asp is due to the absence of L-Asparagine synthetase (ASNS), the enzyme that catalyzes the biosynthesis of L-asparagine. ASNS gene is located on 7q21.3, and its increased expression in ALLs correlates with L-Asp resistance. Chromosome 7 monosomy (-7) is a recurrent aberration in myeloid disorders, particularly in adverse-risk Acute Myeloid Leukemias (AMLs) and therapy-related myeloid neoplasms (t-MN), that leads to a significant downregulation of the deleted genes, including ASNS...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28637675/structure-functional-aspects-of-the-human-riboflavin-transporter-3-slc52a3-role-of-the-predicted-glycosylation-and-substrate-interacting-sites
#2
Veedamali S Subramanian, Subrata Subai, Trevor Teafatiller, Jennifer A Bohl, Hamid M Said
The human riboflavin (RF) transporter-3 (hRFVT-3; product of the SLC52A3 gene) plays an essential role in the intestinal RF absorption process and is expressed exclusively at the apical membrane domain of polarized enterocytes. Previous studies have characterized different physiological/biological aspects of this transporter, but nothing is known about the glycosylation status of the hRFVT-3 protein and role of this modification in its physiology/biology. Additionally, little is known about the residues in the hRFVT-3 protein that interact with the ligand, RF...
June 21, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28633399/the-interfacial-character-of-antibody-paratopes-analysis-of-antibody-antigen-structures
#3
Minh N Nguyen, Mohan R Pradhan, Chandra Verma, Pingyu Zhong
Summary: In this study, computational methods are applied to investigate the general properties of antigen engaging residues of a paratope from a non-redundant dataset of 403 antibody-antigen complexes to dissect the contribution of hydrogen bonds, hydrophobic, van der Waals contacts and ionic interactions, as well as role of water molecules in the antigen-antibody interface. Consistent with previous reports using smaller datasets, we found that Tyr, Trp, Ser, Asn, Asp, Thr, Arg, Gly, His contribute substantially to the interactions between antibody and antigen...
June 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28631054/adaptation-of-tick-borne-encephalitis-virus-from-human-brain-to-different-cell-cultures-induces-multiple-genomic-substitutions
#4
Eugenia P Ponomareva, Vladimir A Ternovoi, Tamara P Mikryukova, Elena V Protopopova, Anastasia V Gladysheva, Alexander N Shvalov, Svetlana N Konovalova, Eugene V Chausov, Valery B Loktev
The C11-13 strain from the Siberian subtype of tick-borne encephalitis virus (TBEV) was isolated from human brain using pig embryo kidney (PEK), 293, and Neuro-2a cells. Analysis of the complete viral genome of the C11-13 variants during six passages in these cells revealed that the cell-adapted C11-13 variants had multiple amino acid substitutions as compared to TBEV from human brain. Seven out of eight amino acids substitutions in the high-replicating C11-13(PEK) variant mapped to non-structural proteins; 13 out of 14 substitutions in the well-replicating C11-13(293) variant, and all four substitutions in the low-replicating C11-13(Neuro-2a) variant were also localized in non-structural proteins, predominantly in the NS2a (2), NS3 (6) and NS5 (3) proteins...
June 19, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28629319/polymorphism-in-asparagine-synthetase-is-associated-with-overall-survival-of-hepatocellular-carcinoma-patients
#5
Wei Li, Chengwei Dong
BACKGROUND: Recently, it is reported that asparagine synthetase (ASNS) is an independent predictor of surgical survival in hepatocellular carcinoma (HCC) patients. It is also reported that activating transcription factor 6 (ATF6) expression is decreased in HCC patients. So in the present study, we explored the relationship between ASNS and ATF6, and whether ASNS expression was associated with HCC. METHODS: ATF6 was over expressed in 3 HCC cell lines (HepG2, HepG2...
June 19, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28621305/structural-insights-into-the-function-of-zranb3-in-replication-stress-response
#6
Marek Sebesta, Christopher D O Cooper, Antonio Ariza, Christopher J Carnie, Dragana Ahel
Strategies to resolve replication blocks are critical for the maintenance of genome stability. Among the factors implicated in the replication stress response is the ATP-dependent endonuclease ZRANB3. Here, we present the structure of the ZRANB3 HNH (His-Asn-His) endonuclease domain and provide a detailed analysis of its activity. We further define PCNA as a key regulator of ZRANB3 function, which recruits ZRANB3 to stalled replication forks and stimulates its endonuclease activity. Finally, we present the co-crystal structures of PCNA with two specific motifs in ZRANB3: the PIP box and the APIM motif...
June 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28620971/the-adipokinetic-hormone-of-the-coleopteran-suborder-adephaga-structure-function-and-comparison-of-distribution-in-other-insects
#7
Gerd Gäde, Heather G Marco
The aim of the current study is to identify the adipokinetic hormone(s) (AKHs) of a basal suborder of the species-rich Coleoptera, the Adephaga, and possibly learn more about the ancestral AKH of beetles. Moreover, we wanted to compare the ancestral AKH with AKHs of more advanced beetles, of which a number are pest insects. This would allow us to assess whether AKH mimetics would be suitable as insecticides, that is, be harmful to the pest species but not to the beneficial species. Nine species of the Adephaga were investigated and all synthesize only one octapeptide in the corpus cardiacum, as revealed by Edman degradation sequencing techniques or by mass spectrometry...
June 16, 2017: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/28620050/engineering-the-fragment-crystallizable-fc-region-of-human-igg1-multimers-and-monomers-to-fine-tune-interactions-with-sialic-acid-dependent-receptors
#8
Patricia A Blundell, Ngoc Phuong Lan Le, Joel Allen, Yasunori Watanabe, Richard J Pleass
Multimeric fragment crystallizable (Fc) regions and Fc-fusion proteins are actively being explored as biomimetic replacements for intravenous immunoglobulin (IVIG) therapy, which is deployed to manage many diseases and conditions but is expensive and not always efficient. The Fc region of human IgG1 (IgG1-Fc) can be engineered into multimeric structures (hexa-Fcs) that bind their cognate receptors with high avidity. The critical influence of the unique N-linked glycan attached at Asn-297 on the structure and function of IgG1-Fc is well documented; however, whether the N-linked glycan has a similarly critical role in multimeric, avidly binding Fcs is unknown...
June 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28617432/bst2-confers-cisplatin-resistance-via-nf-%C3%AE%C2%BAb-signaling-in-nasopharyngeal-cancer
#9
Chun-Mei Kuang, Xiang Fu, Yi-Jun Hua, Wen-di Shuai, Zhi-Hua Ye, Yingchang Li, Qi-Hua Peng, Yi-Zhuo Li, Shuai Chen, Chao-Nan Qian, Wenlin Huang, Ran-Yi Liu
Concurrent/adjuvant cisplatin-based chemoradiotherapy is regarded as the standard of treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). However, patients who do not respond to cisplatin suffer, rather than benefit, from chemotherapy treatment. The goal of this study was to identify molecules involved in cisplatin resistance and to clarify their molecular mechanisms, which would help in the discovery of potential therapeutic targets and in developing a personalized and precise treatment approach for NPC patients...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28609757/a-molecular-docking-study-of-the-interactions-between-human-transferrin-and-seven-metallocene-dichlorides
#10
Jorge R Güette-Fernández, Enrique Meléndez, Wilson Maldonado-Rojas, Carlos Ortega-Zúñiga, Jesus Olivero-Verbel, Elsie I Parés-Matos
Human Transferrin (hTf) is a metal-binding protein found in blood plasma and is well known for its role in iron delivery. With only a 30% of its capacity for Fe(+3) binding, this protein has the potential ability to transport other metal ions or organometallic compounds from the blood stream to all cell tissues. In this perspective, recent studies have described seven metallocene dichlorides (Cp2M(IV)Cl2, M(IV)=V, Mo, W, Nb, Ti, Zr, Hf) suitable as anticancer drugs and less secondary effects than cisplatin...
May 30, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28605180/a-hydrogel-microsphere-drug-delivery-system-that-supports-once-monthly-administration-of-a-glp-1-receptor-agonist
#11
Eric L Schneider, Brian R Hearn, Samuel J Pfaff, Ralph Reid, David G Parkes, Niels Vrang, Gary W Ashley, Daniel V Santi
We have developed a chemically-controlled very long-acting delivery system to support once-monthly administration of a peptidic GLP-1R agonist. Initially, the prototypical GLP-1R agonist exenatide was covalently attached to hydrogel microspheres by a self-cleaving β-eliminative linker; after subcutaneous injection in rats the peptide was slowly released into the systemic circulation. However, the short serum exenatide half-life suggested its degradation in the subcutaneous depot. We found that exenatide undergoes deamidation at Asn(28)with an in vitro and in vivo half-life of approximately two weeks...
June 12, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28604527/spiritual-nursing-care-education-an-integrated-strategy-for-teaching-students
#12
Donna M White, Mikel Hand
The failure of nursing schools to integrate spiritual nursing care education into the curriculum has contributed to a lack in nurses' spiritual care ability. Developing, integrating, and testing a Spiritual Care Nursing Education strategy in an Associates of Science nursing program significantly increased the perceived spiritual care competence of student nurses. Utilizing a faculty team to develop learning activities to address critical spiritual care attributes offers a method to integrate spiritual nursing care content throughout the curriculum in ASN and BSN programs...
July 2017: Journal of Christian Nursing: a Quarterly Publication of Nurses Christian Fellowship
https://www.readbyqxmd.com/read/28602734/molecular-characterization-and-gene-expression-of-cathepsin-l-in-nile-tilapia-oreochromis-niloticus
#13
Fu-Rui Liang, Yue-Hui Hong, Cong-Cong Ye, Hailin Deng, Jian-Ping Yuan, Yun-Fang Hao, Jiang-Hai Wang
Cathepsin L (CatL) has been widely known for its involvement in the innate immunity. However, it still remains poorly understand how CatL modulates the immune system of teleosts. Moreover, the CatL of Nile tilapia (NtCatL) has not been cloned or characterized. In this study, the gene encoding NtCatL was cloned, and was characterized by bioinformatics analysis, heterologous expression and protease activity assay. The coding sequence of NtCatL is 1017 bp in length and encodes 338 amino acid residues with a predicted molecular weight of 38...
June 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28591282/incidence-of-anterior-segment-neovascularization-during-intravitreal-treatment-for-macular-edema-secondary-to-central-retinal-vein-occlusion
#14
Luiz Filipe Adami Lucatto, Octaviano Magalhães-Junior, Juliana M B Prazeres, Adriano M Ferreira, Ramon A Oliveira, Nilva S Moraes, Flávio E Hirai, Mauricio Maia
Purpose: To analyze the effects of injections of intravitreal triamcinolone acetonide (IVTA) and intravitreal bevacizumab (IVB) on the incidence rates of anterior segment neovascularization (ASN) and neovascular glaucoma (NVG) in patients with macular edema secondary to central retinal vein occlusion (CRVO). Methods: In this prospective, randomized, double-masked, sham-controlled study, 35 patients with macular edema following CRVO were randomized to intravitreal bevacizumab, intravitreal triamcinolone acetonide, or sham injections during the first 6 months of the study...
March 2017: Arquivos Brasileiros de Oftalmologia
https://www.readbyqxmd.com/read/28589955/crystal-structures-of-u6-snrna-specific-terminal-uridylyltransferase
#15
Seisuke Yamashita, Yuko Takagi, Takashi Nagaike, Kozo Tomita
The terminal uridylyltransferase, TUT1, builds or repairs the 3'-oligo-uridylylated tail of U6 snRNA. The 3'-oligo-uridylylated tail is the Lsm-binding site for U4/U6 di-snRNP formation and U6 snRNA recycling for pre-mRNA splicing. Here, we report crystallographic and biochemical analyses of human TUT1, which revealed the mechanisms for the specific uridylylation of the 3'-end of U6 snRNA by TUT1. The O2 and O4 atoms of the UTP base form hydrogen bonds with the conserved His and Asn in the catalytic pocket, respectively, and TUT1 preferentially incorporates UMP onto the 3'-end of RNAs...
June 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28585176/the-crystal-structure-of-ac-achbp-in-complex-with-%C3%AE-conotoxin-lvia-reveals-the-mechanism-of-its-selectivity-towards-different-nachr-subtypes
#16
Manyu Xu, Xiaopeng Zhu, Jinfang Yu, Jinpeng Yu, Sulan Luo, Xinquan Wang
The α3* nAChRs, which are considered to be promising drug targets for problems such as pain, addiction, cardiovascular function, cognitive disorders etc., are found throughout the central and peripheral nervous system. The α-conotoxin (α-CTx) LvIA has been identified as the most selective inhibitor of α3β2 nAChRs known to date, and it can distinguish the α3β2 nAChR subtype from the α6/α3β2β3 and α3β4 nAChR subtypes. However, the mechanism of its selectivity towards α3β2, α6/α3β2β3, and α3β4 nAChRs remains elusive...
June 5, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28582518/substitutions-in-pbp3-confer-resistance-to-both-ampicillin-and-extended-spectrum-cephalosporins-in-haemophilus-parainfluenzae-as-revealed-by-site-directed-mutagenesis-and-gene-recombinants
#17
Nanna H Wienholtz, Aynur Barut, Niels Nørskov-Lauritsen
Objectives: To determine the association of amino acid substitutions in PBP3 with β-lactam susceptibility in Haemophilus parainfluenzae . Methods: Single and multiple amino acid mutations at positions 385, 511 and 526 were introduced into PBP3 of a β-lactam-susceptible H. parainfluenzae strain using site-directed mutagenesis. Recombinants were also generated using PCR-amplified ftsI from clinical strains encoding multiple amino acid substitutions. MICs of ampicillin, cefuroxime, cefotaxime and ceftriaxone were determined using Etest ® ...
June 5, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28581021/antimicrobial-peptide-from-bacillus-subtilis-csb138-characterization-killing-kinetics-and-synergistic-potency
#18
Sudip Regmi, Yoon Seok Choi, Yun Hee Choi, Young Kyun Kim, Seung Sik Cho, Jin Cheol Yoo, Joo-Won Suh
We studied the prospect of synergy between the antimicrobial peptide p138c and non-peptide antibiotics for increasing the potency and bacterial killing kinetics of these agents. The production of p138c was maximized in the late exponential growth phase of Bacillus subtilis CSB138. Purification of p138c resulted in a total of 4800 arbitrary units (AU) with 19.15-fold and 3.2% recovery. Peptide p138c was thermo-tolerant up to 50 °C and stable at pH 5.8 to 11. The biochemical nature of p138c was determined by a bioassay, similar to tricine-SDS-PAGE, indicating inhibition at 3 kDa...
March 2017: International Microbiology: the Official Journal of the Spanish Society for Microbiology
https://www.readbyqxmd.com/read/28568505/bola-drb3-gene-polymorphisms-influence-bovine-leukaemia-virus-infection-levels-in-holstein-and-holstein%C3%A2-%C3%A3-%C3%A2-jersey-crossbreed-dairy-cattle
#19
H A Carignano, M J Beribe, M E Caffaro, A Amadio, J P Nani, G Gutierrez, I Alvarez, K Trono, M M Miretti, M A Poli
Bovine leukemia virus (BLV) infections, causing persistent lymphocytosis and lethal lymphosarcoma in cattle, have reached high endemicity on dairy farms. We observed extensive inter-individual variation in the level of infection (LI) by assessing differences in proviral load in peripheral blood. This phenotypic variation appears to be determined by host genetics variants, especially those located in the BoLA-DRB3 MHCII molecule. We performed an association study using sequencing-based typed BOLA-DRB3 alleles from over 800 Holstein and Holstein × Jersey cows considering LI in vivo and accounting for filial relationships...
May 31, 2017: Animal Genetics
https://www.readbyqxmd.com/read/28557433/ligand-mediated-and-enzyme-directed-precise-targeting-and-retention-for-the-enhanced-treatment-of-glioblastoma
#20
Shaobo Ruan, Wei Xiao, Chuan Hu, Huajin Zhang, Jingdong Rao, Sihan Wang, Xiao Wang, Qin He, Huile Gao
Glioblastoma (GBM), one of the most lethal cancers, remains as a hard task to handle. The major hurdle of nanostructured therapeutic agents comes from the limited retention at the GBM site and poor selectivity. In this study, we reported dual-functional gold nanoparticles (AuNPs) to figure out the biological barrier and improve their accumulation in GBM. The nanoparticles, AuNP-A&C-R, were composed of two functional particles: one was Ala-Ala-Asn-Cys-Asp (AK) and R8-RGD-comodified AuNPs (AuNP-AK-R) and the other was 2-cyano-6-amino-benzothiazole and R8-RGD-comodified AuNPs (AuNP-CABT-R)...
June 21, 2017: ACS Applied Materials & Interfaces
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