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https://www.readbyqxmd.com/read/29782552/role-of-kinesins-in-directed-adenovirus-transport-and-cytoplasmic-exploration
#1
Jie Zhou, Julian Scherer, Julie Yi, Richard B Vallee
Many viruses, including adenovirus, exhibit bidirectional transport along microtubules following cell entry. Cytoplasmic dynein is responsible for microtubule minus end transport of adenovirus capsids after endosomal escape. However, the identity and roles of the opposing plus end-directed motor(s) remain unknown. We performed an RNAi screen of 38 kinesins, which implicated Kif5B (kinesin-1 family) and additional minor kinesins in adenovirus 5 (Ad5) capsid translocation. Kif5B RNAi markedly increased centrosome accumulation of incoming Ad5 capsids in human A549 pulmonary epithelial cells within the first 30 min post infection, an effect dramatically enhanced by blocking Ad5 nuclear pore targeting using leptomycin B...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29782246/precision-medicine-and-radiogenomics-in-breast-cancer-new-approaches-toward-diagnosis-and-treatment
#2
Katja Pinker, Joanne Chin, Amy N Melsaether, Elizabeth A Morris, Linda Moy
Precision medicine is medicine optimized to the genotypic and phenotypic characteristics of an individual and, when present, his or her disease. It has a host of targets, including genes and their transcripts, proteins, and metabolites. Studying precision medicine involves a systems biology approach that integrates mathematical modeling and biology genomics, transcriptomics, proteomics, and metabolomics. Moreover, precision medicine must consider not only the relatively static genetic codes of individuals, but also the dynamic and heterogeneous genetic codes of cancers...
June 2018: Radiology
https://www.readbyqxmd.com/read/29782227/cdk5-mediated-acn-acinus-phosphorylation-regulates-basal-autophagy-independently-of-metabolic-stress
#3
Nilay Nandi, Helmut Krämer
In neurons, autophagy counteracts consequences of aging. It is therefore of interest how basal rates of macroautophagy/autophagy can be controlled independently of metabolic stress. We recently investigated the regulation of basal, starvation-independent autophagy by Acn/Acinus, a multifunctional nuclear protein with proposed roles in apoptosis, alternative RNA splicing, and basal autophagy. We found that Acn is stabilized by phosphorylation of the conserved serine 437. The phosphomimetic AcnS437D mutation causes no overt developmental phenotypes, but significantly elevates levels of basal autophagy and extends life spans...
May 21, 2018: Autophagy
https://www.readbyqxmd.com/read/29781975/novel-best1-mutations-detected-by-next-generation-sequencing-in-a-chinese-population-with-vitelliform-macular-dystrophy
#4
Jingli Guo, Fengjuan Gao, Wenyi Tang, Yuhe Qi, Yi Xuan, Wei Liu, Lei Li, Xiaofeng Ye, Gezhi Xu, Jihong Wu, Yongjin Zhang
PURPOSE: To characterize novel BEST1 mutations and the phenotype-genotype correlations in vitelliform macular dystrophy in a Chinese population. METHODS: Seventeen individuals affected by vitelliform macular dystrophy underwent detailed ophthalmic examinations, including a best-corrected visual acuity test, slit-lamp biomicroscopy, fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, and optical coherence tomography angiography...
May 16, 2018: Retina
https://www.readbyqxmd.com/read/29781496/a-universal-platform-for-selection-and-high-resolution-phenotypic-screening-of-bacterial-mutants-using-the-nanowell-slide
#5
H Antypas, M Veses-Garcia, E Weibull, H Andersson-Svahn, A Richter-Dahlfors
The Petri dish and microtiter plate are the golden standard for selection and screening of bacteria in microbiological research. To improve on the limited resolution and throughput of these methods, we developed a universal, user-friendly platform for selection and high-resolution phenotypic screening based on the nanowell slide. This miniaturized platform has an optimal ratio between throughput and assay complexity, holding 672 nanowells of 500 nl each. As monoclonality is essential in bacterial genetics, we used FACS to inoculate each nanowell with a single bacterium in 15 min...
May 21, 2018: Lab on a Chip
https://www.readbyqxmd.com/read/29781137/variants-in-actg2-underlie-a-substantial-number-of-australasian-patients-with-primary-chronic-intestinal-pseudo-obstruction
#6
G Ravenscroft, S Pannell, G O'Grady, R Ong, H C Ee, F Faiz, L Marns, H Goel, P Kumarasinghe, E Sollis, P Sivadorai, M Wilson, A Magoffin, S Nightingale, M-L Freckmann, E P Kirk, R Sachdev, D A Lemberg, M B Delatycki, M A Kamm, C Basnayake, P J Lamont, D J Amor, K Jones, J Schilperoort, M R Davis, N G Laing
BACKGROUND: Primary chronic intestinal pseudo-obstruction (CIPO) is a rare, potentially life-threatening disorder characterized by severely impaired gastrointestinal motility. The objective of this study was to examine the contribution of ACTG2, LMOD1, MYH11, and MYLK mutations in an Australasian cohort of patients with a diagnosis of primary CIPO associated with visceral myopathy. METHODS: Pediatric and adult patients with primary CIPO and suspected visceral myopathy were recruited from across Australia and New Zealand...
May 21, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29779890/high-throughput-screening-enhances-kidney-organoid-differentiation-from-human-pluripotent-stem-cells-and-enables-automated-multidimensional-phenotyping
#7
Stefan M Czerniecki, Nelly M Cruz, Jennifer L Harder, Rajasree Menon, James Annis, Edgar A Otto, Ramila E Gulieva, Laura V Islas, Yong Kyun Kim, Linh M Tran, Timothy J Martins, Jeffrey W Pippin, Hongxia Fu, Matthias Kretzler, Stuart J Shankland, Jonathan Himmelfarb, Randall T Moon, Neal Paragas, Benjamin S Freedman
Organoids derived from human pluripotent stem cells are a potentially powerful tool for high-throughput screening (HTS), but the complexity of organoid cultures poses a significant challenge for miniaturization and automation. Here, we present a fully automated, HTS-compatible platform for enhanced differentiation and phenotyping of human kidney organoids. The entire 21-day protocol, from plating to differentiation to analysis, can be performed automatically by liquid-handling robots, or alternatively by manual pipetting...
May 15, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29779869/genotypic-characteristics-and-their-association-with-phenotypic-characteristics-of-hereditary-medullary-thyroid-carcinoma-in-korea
#8
Kyong Yeun Jung, Seok-Mo Kim, Min Joo Kim, Sun Wook Cho, Bup-Woo Kim, Yong Sang Lee, Jong Ju Jeong, Kee-Hyun Nam, Woong Youn Chung, Kyu Eun Lee, Eun-Jae Chung, Hyo Jeong Kim, Do Joon Park, Myung-Whun Sung, Cheong Soo Park, Bo Young Cho, Young Joo Park, Hang-Seok Chang
BACKGROUND: Hereditary medullary thyroid carcinoma can present as a part of multiple endocrine neoplasia syndrome by rearranged during transfection gene mutation. We evaluated the prevalence of rearranged during transfection gene mutation in patients who have medullary thyroid carcinoma and the correlations of genotype with medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism according to the revised American Thyroid Association risk level. METHODS: A total of 331 patients were diagnosed with medullary thyroid carcinoma, 172 of whom were tested for the rearranged during transfection germline mutation by sequencing of exon 8, 10, 11, and 13-16...
May 17, 2018: Surgery
https://www.readbyqxmd.com/read/29779778/identification-of-tb-e12-as-a-novel-ftsz-inhibitor-with-anti-tuberculosis-activity
#9
Yuan Lin, Hongjuan Zhang, Ningyu Zhu, Xia Wang, Yanxing Han, Minghua Chen, Jiandong Jiang, Shuyi Si
The global pandemic of multidrug-resistant (MDR) Mycobacterium tuberculosis (TB) drives for more effective anti-TB drugs with new drug target. Filamentous temperature sensitive protein Z (FtsZ), a GTP dependent prokaryotic cell division protein, forms a dynamic Z-ring in the center of the cell. Differences between bacterial FtsZ and eukaryotic tubulin make FtsZ a highly attractive drug target. In this study, we used phenotype screening of M. smegmatis and model screening targeting M. tuberculosis FtsZ (Mtb-FtsZ) to identify a hit compound TB-E12...
May 2018: Tuberculosis
https://www.readbyqxmd.com/read/29779767/novel-red-fluorescence-protein-based-microplate-assay-for-drug-screening-against-dormant-mycobacterium-tuberculosis-by-using-paraffin
#10
Amar Yeware, Dhiman Sarkar
The hypoxia model of dormancy is widely used in drug screening programs to identify novel inhibitors against latent Mycobacterium tuberculosis disease. In earlier reported microplate assays, hypoxia was maintained by either sealing the microplate or shifting in an anaerobic chamber to develop dormant phenotype. In these assays, inhibitors were added during inoculation, which mainly represents the active stage inhibitors instead of the dormant ones. Herein, the culture was covered with paraffin to develop hypoxia condition and consequently providing the advantage of adding compounds at any stage during incubation of 96-well plate...
May 2018: Tuberculosis
https://www.readbyqxmd.com/read/29779206/old-new-and-emerging-immunohistochemical-markers-in-pheochromocytoma-and-paraganglioma
#11
REVIEW
Veronica K Y Cheung, Anthony J Gill, Angela Chou
The evolution of genetic research over the past two decades has greatly improved the understanding of pheochromocytomas and paragangliomas. It is now accepted that more than one third of pheochromocytoma and paragangliomas arise in the context of syndromic disease, usually hereditary. The genetic profile of these tumors also has important prognostic implications which may help guide treatment. Accompanying the changing molecular landscape is the development of new immunohistochemical markers. Initially used in assisting with diagnosis, immunohistochemical markers have now become an important adjunct to screening programs for inherited conditions and subsequently as prognostic markers...
May 19, 2018: Endocrine Pathology
https://www.readbyqxmd.com/read/29779058/genetics-of-resistant-hypertension-the-missing-heritability-and-opportunities
#12
REVIEW
Samantha K Teixeira, Alexandre C Pereira, Jose E Krieger
PURPOSE OF THE REVIEW: Blood pressure regulation in humans has long been known to be a genetically determined trait. The identification of causal genetic modulators for this trait has been unfulfilling at the least. Despite the recent advances of genome-wide genetic studies, loci associated with hypertension or blood pressure still explain a very low percentage of the overall variation of blood pressure in the general population. This has precluded the translation of discoveries in the genetics of human hypertension to clinical use...
May 19, 2018: Current Hypertension Reports
https://www.readbyqxmd.com/read/29778388/androgen-excess-polycystic-ovary-syndrome-society-position-statement-on-depression-anxiety-quality-of-life-and-eating-disorders-in-polycystic-ovary-syndrome
#13
Anuja Dokras, Elisabeth Stener-Victorin, Bulent O Yildiz, Rong Li, Sasha Ottey, Duru Shah, Neill Epperson, Helena Teede
OBJECTIVE: To formulate clinical consensus recommendations for screening depression, anxiety, health-related quality of life (HRQoL), and disordered eating symptoms in women with polycystic ovary syndrome (PCOS) and review prevalence based on phenotypes and ethnicity, changes over time, etiology, and impact of treatment. DESIGN: Systematic reviews and preparation of position statement. SETTING: Not applicable. PATIENT(S): Women with PCOS and controls screened using validated tools...
May 2018: Fertility and Sterility
https://www.readbyqxmd.com/read/29776909/a-bispecific-antibody-targeting-her2-and-her3-suppresses-tumor-growth
#14
(no author information available yet)
Unbiased phenotypic combinatorial screening uncovers a bispecific antibody (bAb) targeting HER2 and HER3.
May 18, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29776438/uninterrupted-monitoring-of-drug-effects-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-with-bioluminescence-ca-2-microscopy
#15
Kazushi Suzuki, Takahito Onishi, Chieko Nakada, Shunsuke Takei, Matthew J Daniels, Masahiro Nakano, Tomoki Matsuda, Takeharu Nagai
OBJECTIVE: Cardiomyocytes derived from human-induced pluripotent stem cells are a powerful platform for high-throughput drug screening in vitro. However, current modalities for drug testing, such as electrophysiology and fluorescence imaging have inherent drawbacks. To circumvent these problems, we report the development of a bioluminescent Ca2+ indicator GmNL(Ca2+ ), and its application in a customized microscope for high-throughput drug screening. RESULTS: GmNL(Ca2+ ) gives a 140% signal change with Ca2+ , and can image drug-induced changes of Ca2+ dynamics in cultured cells...
May 18, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29775797/functional-screening-of-selective-mitochondrial-inhibitors-of-plasmodium
#16
Maria G Gomez-Lorenzo, Ane Rodríguez-Alejandre, Sonia Moliner-Cubel, María Martínez-Hoyos, Noemí Bahamontes-Rosa, Rubén Gonzalez Del Rio, Carolina Ródenas, Jesús de la Fuente, Jose Luis Lavandera, Jose F García-Bustos, Alfonso Mendoza-Losana
Phenotypic screening has produced most of the new chemical entities currently in clinical development for malaria, plus many lead compounds active against Plasmodium falciparum asexual stages. However, lack of knowledge about the mode of action of these compounds delays and may even hamper their future development. Identifying the mode of action of the inhibitors greatly helps to prioritise compounds for further development as novel antimalarials. Here we describe a whole-cell method to detect inhibitors of the mitochondrial electron transport chain, using oxygen consumption as high throughput readout in 384-well plate format...
May 9, 2018: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29775789/e-coli-encoding-blandm-5-associated-with-community-acquired-uti-cases-with-unusual-mic-creep-like-phenomenon-against-imipenem
#17
Varsha Rani Gajamer, Amitabha Bhattacharjee, Deepjyoti Paul, Chandrayee Deshamukhya, Ashish Kr Singh, Nilu Pradhan, Hare Krishna Tiwari
OBJECTIVES: Carbapenemase-producing Escherichia coli are of major clinical concern. The present study aimed to identify NDM-5 producing E.coli associated with community-acquired urinary tract infection, co-harboring ESBL genes and a pattern of imipenem MIC creep. METHODS: A total of 973 urine samples were collected from females of age between 18-49 diagnosed with UTI. Isolates were identified by standard microbiological procedures. Presence of blaNDM and ESBL genes was determined by PCR assay and sequencing...
May 15, 2018: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29775727/isolation-structure-elucidation-and-antibacterial-activity-of-methyl-4-8-dimethylundecanate-from-the-marine-actinobacterium-streptomyces-albogriseolus-ecr64
#18
Durairaj Thirumurugan, Ramasamy Vijayakumar, Chithravel Vadivalagan, Pushparaj Karthika, Md Khurshid Alam Khan
Around 120 actinobacterial colonies were isolated from various regions of marine East coast region of Tamil Nadu, India. Among them, 33 were morphologically distinct and they were preliminarily screened for their antibacterial activity against Pseudomonas fluorescens, Vibrio cholerae, V. parahaemolyticus, V. alginolyticus, and Aeromonas hydrophila by cross-streak plate technique. Among the isolated, the isolate ECR64 exhibited maximum zone of inhibition against fish pathogenic bacteria. The crude bioactive compounds were extracted from the isolate ECR64 using different organic solvents which exhibited maximum antibacterial activity...
May 15, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29775684/virulence-determinants-biofilm-production-and-antimicrobial-susceptibility-in-staphylococcus-aureus-causing-device-associated-infections-in-a-tunisian-hospital
#19
I Mesrati, M Saidani, M Jemili, S Ferjeni, A Slim, I Boutiba-Ben Boubaker
Staphylococcus aureus is clinically relevant pathogen that cause device-related infections driven by several virulence factors. In this study we characterize S. aureus isolates involved in medical device-related infections in Tunisian patients. Forty consecutive S. aureus strains causing device-related infections (DRI group) and 47 randomly selected S. aureus strains causing non-device-related infections (NDRI group) were collected. All strains were phenotypically screened for antibiotic susceptibility and biofilm forming ability...
May 15, 2018: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29775598/selective-cytotoxicity-of-the-nampt-inhibitor-fk866-toward-gastric-cancer-cells-with-markers-of-the-epithelial-mesenchymal-transition-due-to-loss-of-naprt
#20
Jooyoung Lee, Hyosil Kim, Jae Eun Lee, Su-Jin Shin, Sejin Oh, Sungjin Kwon, Hakhyun Kim, Yoon Young Choi, Michael A White, Soonmyung Paik, Jae-Ho Cheong, Hyun Seok Kim
BACKGROUND & AIMS: Markers of the epithelial-mesenchymal transition (EMT) in gastric tumor tissues are associated with poor outcomes of patients. We performed a screen to identify pharmacologic compounds that kill gastric cancer cells with EMT-associated gene expression patterns and investigate their mechanisms. METHODS: We identified 29 gastric cancer cell lines with gene expression signature previously associated with an EMT subtype, based on data from RNA sequence analyses, and confirmed their mesenchymal phenotypes of 7 lines (Hs746T, SNU1750, MKN1, SK4, SNU484, SNU668, and YCC11), based in invasive activity and protein markers...
May 15, 2018: Gastroenterology
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