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https://www.readbyqxmd.com/read/28645195/mutational-biases-influence-parallel-adaptation
#1
Arlin Stoltzfus, David M McCandlish
While mutational biases strongly influence neutral molecular evolution, the role of mutational biases in shaping the course of adaptation is less clear. Here we consider the frequency of transitions relative to transversions among adaptive substitutions. Because mutation rates for transitions are higher than those for transversions, if mutational biases influence the dynamics of adaptation, then transitions should be over-represented among documented adaptive substitutions. To test this hypothesis, we assembled 2 sets of data on putatively adaptive amino acid replacements that have occurred in parallel during evolution, either in nature or in the laboratory...
June 22, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28645186/igf-i-gene-therapy-in-aging-rats-modulates-hippocampal-genes-relevant-to-memory-function
#2
Joaquín Pardo, Martin C Abba, Ezequiel Lacunza, Olalekan M Ogundele, Isabel Paiva, Gustavo R Morel, Tiago F Outeiro, Rodolfo G Goya
In rats, learning and memory performance decline during normal aging, which makes this rodent species a suitable model to evaluate therapeutic strategies. In aging rats, insulin-like growth factor-I (IGF-I), is known to significantly improve spatial memory accuracy as compared to control counterparts. A constellation of gene expression changes underlie the hippocampal phenotype of aging but no studies on the effects of IGF-I on the hippocampal transcriptome of old rodents have been documented. Here, we assessed the effects of IGF-I gene therapy on spatial memory performance in old female rats and compared them with changes in the hippocampal transcriptome...
June 22, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28644958/translating-cancer-epigenomics-into-the-clinic-focus-on-lung-cancer
#3
REVIEW
Josep Mari-Alexandre, Angel Diaz-Lagares, Maria Villalba, Oscar Juan, Ana B Crujeiras, Alfonso Calvo, Juan Sandoval
Epigenetic deregulation is increasingly being recognized as a hallmark of cancer. Recent studies have identified many new epigenetic biomarkers, some of which are being introduced into clinical practice for diagnosis, molecular classification, prognosis or prediction of response to therapies. O-6-methylguanine-DNA methyltransferase gene is the most clinically advanced epigenetic biomarker as it predicts the response to temozolomide and carmustine in gliomas. Therefore, epigenomics may represent a novel and promising tool for precision medicine, and in particular, the detection of epigenomic biomarkers in liquid biopsies will be of great interest for monitoring diseases in patients...
June 2, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28644752/expression-and-purification-of-swine-rag2-in-e-coli-for-production-of-porcine-rag2-polyclonal-antibodies
#4
Yu-Bei Jin, Wen-Tao Yang, Ke-Yan Huang, Hong-Liang Chen, Seria-Masole Shonyela, Jing Liu, Qiong Liu, Bo Feng, You Zhou, Shu-Li Zhi, Yan-Long Jiang, Jian-Zhong Wang, Hai-Bin Huang, Chun-Wei Shi, Gui-Lian Yang, Chun-Feng Wang
Recombination activating gene 2 (RAG2) is necessary for immature B cell differentiation. Antibodies to human and rabbit RAG2 are currently commercially available, but antibodies to swine RAG remain unavailable to date. In this study, the swine RAG2 genes sequence was synthesized and then cloned into a pET-28a vector. The recombinant fusion protein was successfully expressed in E. coli, purified through nickel column chromatography, and further digested with Tobacco Etch Virus protease. The cleaved protein was purified by molecular-exclusion chromatography and named pRAG2...
June 23, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28644734/high-throughput-phenotypic-screening-of-kinase-inhibitors-to-identify-drug-targets-for-polycystic-kidney-disease
#5
Tijmen H Booij, Hester Bange, Wouter N Leonhard, Kuan Yan, Michiel Fokkelman, Steven J Kunnen, Johannes G Dauwerse, Yu Qin, Bob van de Water, Gerard J P van Westen, Dorien J M Peters, Leo S Price
Polycystic kidney disease (PKD) is a prevalent disorder characterized by renal cysts that lead to kidney failure. Various signaling pathways have been targeted to stop disease progression, but most interventions still focus on alleviating PKD-associated symptoms. The mechanistic complexity of the disease, as well as the lack of functional in vitro assays for compound testing, has made drug discovery for PKD challenging. To identify modulators of PKD, Pkd1(-/-) kidney tubule epithelial cells were applied to a scalable and automated 3D cyst culture model for compound screening, followed by phenotypic profiling to determine compound efficacy...
June 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28644686/cervical-adenocarcinoma-diagnosis-of-human-papillomavirus-positive-and-human-papillomavirus-negative-tumors
#6
Edyta C Pirog
CONTEXT: - Cervical adenocarcinomas span a diverse group of tumors with several distinct histologic tumor types, which include endocervical, endometrioid, intestinal, villoglandular, gastric, signet ring, serous, clear cell, and mesonephric. Diagnosis of cervical adenocarcinoma, especially early diagnosis, poses a significant challenge. OBJECTIVE: - To review the pathogenesis, diagnostic criteria, immunohistochemical markers, and differential diagnosis of various subtypes of human papillomavirus (HPV)-positive and HPV-negative cervical adenocarcinomas...
June 23, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28644624/extensive-assessment-of-various-computational-methods-for-aspartate-s-pka-shift
#7
Zhaoxi Sun, Xiaohui Wang, Jianing Song
A series of computational methods for pKa shift prediction are extensively tested on a set of benchmark protein systems, aiming at identifying pitfalls and evaluating their performance on high variants. Including 19 ASP residues in 10 protein systems, the benchmark set consists of both residues with highly shifted pKa values as well as those varying little from the reference value, with an experimental RMS free energy differences of 2.49 kcal/mol with respect to blocked amino acid, namely the RMS pKa shift being 1...
June 23, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28644550/biphasic-liquid-crystal-and-the-simultaneous-measurement-of-isotropic-and-anisotropic-parameters-by-spatially-resolved-nmr-spectroscopy
#8
Malin Reller, Svenja Wesp, Martin R M Koos, Michael Knut Reggelin, Burkhard Luy
Residual dipolar couplings and other anisotropic NMR parameters are powerful tools for molecular structure elucidation when conventional techniques do not suffice. With current liquid crystalline preparations, it is necessary to prepare two samples to extract isotropic and anisotropic data from spectra and to derive the residual dipolar couplings. Here, we present the preparation, measurement, and interpretation of a novel biphasic liquid crystalline phase where a single sample can be used to generate both isotropic and anisotropic data...
June 23, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28644500/in-situ-nanomechanical-characterization-of-multi-layer-mos2-membranes-from-intraplanar-to-interplanar-fracture
#9
Peifeng Li, Chenchen Jiang, Shang Xu, Yu Zhuang, Libo Gao, Alice Hu, Hongtao Wang, Yang Lu
Layered molybdenum disulfide (MoS2) exhibits rich electronic and optical properties and possesses vastly differing characteristic dimensions. A multi-layer MoS2 membrane represents the critical hierarchical structure which bridges the length-scale of monolayer and bulk material architectures. In this study, the in-plane mechanical properties of MoS2 membranes were investigated by in situ SEM tensile testing. Under the uniaxial tensile loading, brittle fracture caused failure in a highly localized region of the MoS2 membranes and their mechanical properties showed a thickness effect: the strengths of the relatively thicker MoS2 membranes (thickness around hundreds of nanometers) distribute from ∼100 to ∼250 MPa, while the corresponding values of the MoS2 nanosheets (thickness around tens of nanometers) increase significantly to more than 1 GPa...
June 23, 2017: Nanoscale
https://www.readbyqxmd.com/read/28644174/resident-education-in-molecular-and-genetic-testing-in-dermatology-an-opportunity-not-to-be-missed
#10
Michael J Murphy, Kristen Russomanno
No abstract text is available yet for this article.
June 16, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28644055/regulation-of-transient-receptor-potential-melastatin-4-channel-by-sarcoplasmic-reticulum-inositol-triphosphate-receptors-role-in-human-detrusor-smooth-muscle-function
#11
Aaron Provence, Eric S Rovner, Georgi V Petkov
We recently reported key physiological roles for Ca(2+)-activated transient receptor potential melastatin 4 (TRPM4) channels in detrusor smooth muscle (DSM). However, the Ca(2+)-signaling mechanisms governing TRPM4 channel activity in human DSM cells are unexplored. As the TRPM4 channels are activated by Ca(2+), inositol 1,4,5-trisphosphate receptor (IP3R)-mediated Ca(2+) release from the sarcoplasmic reticulum represents a potential Ca(2+) source for TRPM4 channel activation. We used clinically-characterized human DSM tissues to investigate the molecular and functional interactions of the IP3Rs and TRPM4 channels...
June 23, 2017: Channels
https://www.readbyqxmd.com/read/28643929/in-silico-and-functional-evaluation-of-pth1r-mutations-found-in-patients-with-primary-failure-of-eruption-pfe
#12
H M Hendricks, S Bencharit, W Seaman, S A Frazier-Bowers
OBJECTIVES: The genetic basis of PFE (OMIM ID: 125350) was interrogated using molecular functional studies. PFE is a disorder that results in a poor prognosis in the eruption of teeth and by extension, in treatment with a continuous archwire. We tested the hypothesis that PTH1R mutations result in loss of function due to altered protein structure to determine (i) the fate of a functional PTH1R mutation and (ii) the resulting PTH1R protein structure of each functional mutation. METHODS: We used immunofluorescence assay of COS7 cells that were transfected with either the WT or 1092delG PTH1R mutation sequence to compare the fate of the expressed protein...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28643912/mouse-models-for-the-study-of-cranial-base-growth-and-anomalies
#13
REVIEW
S R Vora
The cranial base is a central and integral component of the cranioskeleton, yet little is known about its growth. Despite the dissimilarities between human and murine cranioskeletal form, mouse models are proving instrumental in studying craniofacial growth. The objectives of this review are to summarize recent findings from numerous mouse models that display growth defects in one or more cranial base synchondroses, with accompanying changes in chondrocyte cellular zones. Many of these models also display altered growth of the cranial vault and/or the facial region...
June 2017: Orthodontics & Craniofacial Research
https://www.readbyqxmd.com/read/28643846/feeding-behaviour-of-generalist-pests-on-brassica-juncea-implication-for-manipulation-of-glucosinolate-biosynthesis-pathway-for-enhanced-resistance
#14
Pawan Kumar, Rehna Augustine, Amarjeet Kumar Singh, Naveen C Bisht
Differential accumulation of plant defense metabolites has been suggested to have important ecological consequence in the context of plant-insect interactions. Feeding of generalist pests on Brassica juncea showed a distinct pattern with selective exclusion of leaf margins which are high in glucosinolates. Molecular basis of this differential accumulation of glucosinolates could be explained based on differential expression profile of BjuMYB28 homologs, the major biosynthetic regulators of aliphatic glucosinolates, as evident from quantitative real-time PCR and promoter:GUS fusion studies in allotetraploid B...
June 23, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28643762/serum-butyrylcholinesterase-and-zinc-in-breast-cancer
#15
Rupesh Kumar, Sairoz Razab, Krishnananda Prabhu, Satadru Ray, Bhanu Prakash
CONTEXT: Even though, a large number of serological, molecular markers have been proposed for breast cancer screening, most of them lack specificity, sensitivity, prognostic value, and cost effectiveness. Butyrylcholinesterase (BChE) and its genes are aberrantly expressed in a variety of human cancers. It has-been linked to tumorigenesis, cell proliferation, and cell differentiation. Zinc (Zn) is a cofactor for superoxide dismutase, an enzyme that protects cellular components against free radical-induced damage and carcinogenesis...
April 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28643520/main-plant-extracts-active-properties-effective-on-scopolamine-induced-memory-loss
#16
Ioana-Miruna Balmus, Alin Ciobica
Alzheimer's disease leads to progressive cognitive function loss, which may impair both intellectual capacities and psychosocial aspects. Although the current knowledge points to a multifactorial character of Alzheimer's disease, the most issued pathological hypothesis remains the cholinergic theory. The main animal model used in cholinergic theory research is the scopolamine-induced memory loss model. Although, in some cases, a temporary symptomatic relief can be obtained through targeting the cholinergic or glutamatergic neurotransmitter systems, no current treatment is able to stop or slow cognitive impairment...
January 1, 2017: American Journal of Alzheimer's Disease and Other Dementias
https://www.readbyqxmd.com/read/28643517/a-novel-strategy-for-comprehensive-profiling-and-identification-of-acidic-glycosphingolipids-using-ultra-high-performance-liquid-chromatography-coupled-with-quadrupole-time-of-flight-mass-spectrometry
#17
Ting Hu, Zhixin Jia, Jinlan Zhang
Acidic glycosphingolipids (AGSLs), which mainly consist of ganglioside and sulfatide moieties, are highly concentrated in the central nervous system. Comprehensive profiling of AGSLs has historically been challenging because of their high complexity and the lack of standards. In this paper, a novel strategy was developed to comprehensively profile AGSLs using ultra-high-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS). Ganglioside isomers with different glycan chains such as GD1a/ GD1b were completely separated on a C18 column for the first time to our knowledge, facilitated by the addition of formic acid in the mobile phase...
June 23, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28643489/comparison-of-the-luminex-xtag-respiratory-viral-panel-fast-v2-assay-with-anyplex-ii-rv16-detection-kit-and-advansure-rv-real-time-rt-pcr-assay-for-the-detection-of-respiratory-viruses
#18
Dae Hyun Ko, Hyun Soo Kim, Jungwon Hyun, Han Sung Kim, Jae Seok Kim, Kyoung Un Park, Wonkeun Song
BACKGROUND: The accurate and rapid identification of the causative viruses is important for the timely diagnosis and management of respiratory infections. Multiplex molecular diagnostic techniques have been widely adopted to detect respiratory viruses. We compared the results of a newly upgraded, multiplex, molecular bead-based respiratory viral panel (RVP) assay with the results of Anyplex II RV16 detection kit and AdvanSure RV real-time RT-PCR assay. METHODS: We tested 254 respiratory specimens and cultured viral strains using the Luminex xTAG RVP Fast v2 assay (Luminex Molecular Diagnostics, Canada) and Anyplex II RV16 detection kit and compared the results...
September 2017: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/28643389/combined-molecular-modelling-and-3d-qsar-study-for-understanding-the-inhibition-of-nqo1-by-heterocyclic-quinone-derivatives
#19
Claudia Lopez-Lira, Jans H Alzate-Morales, Margot Paulino, Jaime Mella-Raipán, Cristian O Salas, Ricardo A Tapia, Jorge Soto-Delgado
A combination of three-dimensional quantitative structure-activity relationship (3D-QSAR), and molecular modelling methods were used to understand the potent inhibitory NAD(P)H:quinone oxidoreductase 1 (NQO1) activity of a set of 52 heterocyclic quinones. Molecular docking results indicated that some favourable interactions of key amino acid residues at the binding site of NQO1 with these quinones, would be responsible for an improvement of the NQO1 activity of these compounds. The main interactions involved are hydrogen bond of the amino group of residue Tyr128, π-stacking interactions with Phe106 and Phe178, and electrostatic interactions with flavin adenine dinucleotide (FADH) cofactor...
June 23, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28643361/screening-for-del-phenotype-in-rhd-negative-indians
#20
Swati Kulkarni, Disha S Parchure, Vidya Gopalkrishnan, Manisha Madkaikar
BACKGROUND: DEL phenotype represents a very weak form of D variant detected only by adsorption and elution technique. DEL phenotype individuals mistyped as RhD-negative can lead to alloimmunization after transfusion or pregnancy. Molecular techniques have now been used to identify DEL variants. They are commonly encountered in the East Asian population with RHD(K409K) being the most frequent allele. RHD(M295I) is the most common DEL allele in Caucasians. As there is a paucity of data on DEL phenotype in the Indian population, the study aims to screen RhD negative individuals for two most common DEL mutations...
June 23, 2017: Journal of Clinical Laboratory Analysis
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