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Phenotypic screen

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https://www.readbyqxmd.com/read/28732272/screening-of-the-open-scaffolds-collection-from-compounds-australia-identifies-a-new-chemical-entity-with-anthelmintic-activities-against-different-developmental-stages-of-the-barber-s-pole-worm-and-other-parasitic-nematodes
#1
Sarah Preston, Yaqing Jiao, Jonathan B Baell, Jennifer Keiser, Simon Crawford, Anson V Koehler, Tao Wang, Moana M Simpson, Ray M Kaplan, Karla J Cowley, Kaylene J Simpson, Andreas Hofmann, Abdul Jabbar, Robin B Gasser
The discovery and development of novel anthelmintic classes is essential to sustain the control of socioeconomically important parasitic worms of humans and animals. With the aim of offering novel, lead-like scaffolds for drug discovery, Compounds Australia released the 'Open Scaffolds' collection containing 33,999 compounds, with extensive information available on the physicochemical properties of these chemicals. In the present study, we screened 14,464 prioritised compounds from the 'Open Scaffolds' collection against the exsheathed third-stage larvae (xL3s) of Haemonchus contortus using recently developed whole-organism screening assays...
May 28, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28732199/catch-shiny-droplets-in-suspension-finding-the-needle-in-a-haystack
#2
Nina V Hein-Fuchs, Renate König
In a recent issue of Cell Chemical Biology, Chaipan et al. (2017) described a high-throughput screening methodology to identify epitopes on HIV-1 particles recognized by broadly neutralizing antibodies. The approach utilizes a droplet-based microfluidics platform combining robust phenotypic single-virus sorting with next-generation sequencing of viral quasispecies.
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28732198/primary-cell-phenotypic-screening-illuminates-adrs-and-aops
#3
Audrey J Bone, Keith A Houck
Preclinical, in vitro screening for adverse drug reactions continues to present challenges in the field of drug development. In this issue of Cell Chemical Biology, Shah et al. (2017) employ a phenotypic screening strategy using a panel of human primary cells to define a signature response and an adverse outcome pathway for delayed type IV skin hypersensitivity.
July 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28731911/expert-and-self-assessment-of-lifetime-symptoms-and-diagnosis-of-major-depressive-disorder-in-large-scale-genetic-studies-in-the-general-population-comparison-of-a-clinical-interview-and-a-self-administered-checklist
#4
Jessica Martin, Fabian Streit, Jens Treutlein, Maren Lang, Josef Frank, Andreas J Forstner, Franziska Degenhardt, Stephanie H Witt, Thomas G Schulze, Sven Cichon, Markus M Nöthen, Marcella Rietschel, Jana Strohmaier
Major depression disorder (MDD) is a complex neuropsychiatric disorder and an increasing number of genetic risk variants are being identified. Investigation of their influence in the general population requires accurate and efficient assessment of depressive symptoms. Here, clinical interviews conducted by clinicians are the gold standard. We investigated whether valid and reliable clinical phenotypes can be obtained efficiently using self-administered instruments. Lifetime depressive symptoms and lifetime MDD diagnosis were assessed in 464 population-based individuals using a clinical interview and a structured, self-administered checklist...
July 20, 2017: Psychiatric Genetics
https://www.readbyqxmd.com/read/28731783/identification-of-sppl2a-inhibitors-by-multiparametric-analysis-of-a-high-content-ultra-high-throughput-screen
#5
Xian Zhang, Marjo Götte, Yvonne Ibig-Rehm, Ansgar Schuffenhauer, Marion Kamke, Dan Beisner, Danilo Guerini, Daniela Siebert, Ghislain M C Bonamy, Daniela Gabriel, Ursula Bodendorf
The intramembrane protease signal peptide peptidase-like 2a (SPPL2a) is a potential drug target for the treatment of autoimmune diseases due to an essential role in B cells and dendritic cells. To screen a library of 1.4 million compounds for inhibitors of SPPL2a, we developed an imaging assay detecting nuclear translocation of the proteolytically released cytosolic substrate fragment. The state-of-the-art hit calling approach based on nuclear translocation resulted in numerous false-positive hits, mainly interrupting intracellular protein trafficking...
July 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28731526/drug-discovery-and-development-for-rare-genetic-disorders
#6
REVIEW
Wei Sun, Wei Zheng, Anton Simeonov
Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed...
July 21, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28730149/review-of-antibiotic-resistance-in-the-indian-ocean-commission-a-human-and-animal-health-issue
#7
REVIEW
Noellie Gay, Olivier Belmonte, Jean-Marc Collard, Mohamed Halifa, Mohammad Iqbal Issack, Saindou Mindjae, Philippe Palmyre, Abdul Aziz Ibrahim, Harena Rasamoelina, Loïc Flachet, Laurent Filleul, Eric Cardinale
Antimicrobial resistance (AMR) is a major threat to human, animal health, and environment worldwide. For human, transmission occurred through a variety of routes both in health-care settings and community. In animals, AMR was reported in livestock, pets, and wildlife; transmission of AMR can be zoonotic with the probably most important route being foodborne transmission. The Indian Ocean Commission (IOC), composed of Comoros, Madagascar, Mauritius, Reunion (France), and Seychelles recognized the surveillance of AMR in both animal and human as a main public health priority for the region...
2017: Frontiers in Public Health
https://www.readbyqxmd.com/read/28729648/a-haplotype-in-cfh-family-genes-confers-high-risk-of-rare-glomerular-nephropathies
#8
Yin Ding, Weiwei Zhao, Tao Zhang, Hao Qiang, Jianping Lu, Xin Su, Shuzhen Wen, Feng Xu, Mingchao Zhang, Haitao Zhang, Caihong Zeng, Zhihong Liu, Huimei Chen
Despite distinct renal lesions, a series of rare glomerular nephropathies are reportedly mediated by complement overactivation. Genetic variations in complement genes contribute to disease risk, but the relationship of genotype to phenotype has not been straightforward. Here, we screened 11 complement genes from 91 patients with atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G) and membranoproliferative glomerulonephritis type I (MPGN I), and identified the concomitant presence of three missense variations located within the human complement Factor H (CFH) gene cluster...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729156/multivariate-pattern-analysis-utilizing-structural-or-functional-mri-in-individuals-with-musculoskeletal-pain-and-healthy-controls-a-systematic-review
#9
REVIEW
Ashley Smith, Marina López-Solà, Katie McMahon, Ashley Pedler, Michele Sterling
OBJECTIVE: The purpose of this systematic review is to systematically review the evidence relating to findings generated by multivariate pattern analysis (MVPA) following structural or functional magnetic resonance imaging (fMRI) to determine if this analysis is able to: a) Discriminate between individuals with musculoskeletal pain and healthy controls, b) Predict pain perception in healthy individuals stimulated with a noxious stimulus compared to those stimulated with a non-noxious stimulus...
June 15, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/28727126/the-incidence-of-metabolic-syndrome-in-adolescents-with-different-phenotypes-of-pcos
#10
Kubra Zengin Altintas, Berna Dilbaz, Derya Akdag Cirik, Runa Ozelci, Tuba Zengin, Osman Nuri Erginay, Serdar Dilbaz
OBJECTIVES: To evaluate the incidence of metabolic syndrome in Turkish adolescents with different phenotypes of polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: This cross-sectional study was performed on the Youth Center clinic of a tertiary referral hospital in Turkey. Adolescents with PCOS (n = 144) were classified into four phenotype groups according to the presence of oligo/anovulation (O), hyperandrogenism (H), and polycystic ovarian morphology (P) as follows: Phenotype A (O + H + P), Phenotype B (H + O), Phenotype C (H + P), Phenotype D (O + P)...
2017: Ginekologia Polska
https://www.readbyqxmd.com/read/28726111/glucokinase-mutations-in-pediatric-patients-with-impaired-fasting-glucose
#11
C Aloi, A Salina, N Minuto, R Tallone, F Lugani, A Mascagni, O Mazza, M Cassanello, M Maghnie, G d'Annunzio
AIMS: Our aim was to detect the frequency of glucokinase (GCK) gene mutations in a cohort of patients with impaired fasting glucose and to describe the clinical manifestations of identified variants. We also aimed at predicting the effect of the novel missense mutations by computational approach. METHODS: Overall 100 unrelated Italian families with impaired fasting glucose were enrolled and subdivided into two cohorts according to strict and to mild criteria for diagnosis of maturity-onset diabetes of the young (MODY)...
July 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28725987/gene-mutation-spectrum-and-genotype-phenotype-correlation-in-a-cohort-of-chinese-osteogenesis-imperfecta-patients-revealed-by-targeted-next-generation-sequencing
#12
Y Liu, Asan, D Ma, F Lv, X Xu, J Wang, W Xia, Y Jiang, O Wang, X Xing, W Yu, J Wang, J Sun, L Song, Y Zhu, H Yang, J Wang, M Li
The achievement of more accurate diagnosis would greatly benefit the management of patients with osteogenesis imperfecta (OI). In this study, we present the largest OI sample in China as screened by next generation sequencing. In particular, we successfully identified 81 variants, which included 45 novel variants. We further did a genotype-phenotype analysis, which helps make a better understanding of OI. INTRODUCTION: This study aims to reveal the gene mutation spectrum and the genotype-phenotype relationship among Chinese OI patients by next generation sequencing (NGS)...
July 19, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28725025/an-atypical-case-of-spg56-cyp2u1-related-spastic-paraplegia-presenting-with-delayed-myelination
#13
Gaku Minase, Satoko Miyatake, Shin Nabatame, Hiroshi Arai, Eriko Koshimizu, Takeshi Mizuguchi, Mitsuko Nakashima, Noriko Miyake, Hirotomo Saitsu, Toshinobu Miyamoto, Kazuo Sengoku, Naomichi Matsumoto
Hereditary spastic paraplegia (HSP) is a neurological disorder characterized by a progressive spasticity and muscle weakness of the lower limbs. It is divided into two subtypes, uncomplicated and complicated forms. Biallelic mutations in the cytochrome P450 2U1 gene (CYP2U1) are associated with spastic paraplegia type 56 (SPG56), manifesting both uncomplicated and complicated HSP. Accompanying clinical features include intellectual disability, dystonia, cerebellar ataxia, subclinical peripheral neuropathy, visual impairment, as well as abnormalities in brain magnetic resonance imaging...
July 20, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28724391/hormone-receptor-status-of-a-first-primary-breast-cancer-predicts-contralateral-breast-cancer-risk-in-the-wecare-study-population
#14
Anne S Reiner, Charles F Lynch, Julia S Sisti, Esther M John, Jennifer D Brooks, Leslie Bernstein, Julia A Knight, Li Hsu, Patrick Concannon, Lene Mellemkjær, Marc Tischkowitz, Robert W Haile, Ronglai Shen, Kathleen E Malone, Meghan Woods, Xiaolin Liang, Monica Morrow, Jonine L Bernstein
BACKGROUND: Previous population-based studies have described first primary breast cancer tumor characteristics and their association with contralateral breast cancer (CBC) risk. However, information on influential covariates such as treatment, family history of breast cancer, and BRCA1/2 mutation carrier status was not available. In a large, population-based, case-control study, we evaluated whether tumor characteristics of the first primary breast cancer are associated with risk of developing second primary asynchronous CBC, overall and in subgroups of interest, including among BRCA1/2 mutation non-carriers, women who are not treated with tamoxifen, and women without a breast cancer family history...
July 19, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28723932/the-nucleoid-occlusion-factor-noc-controls-dna-replication-initiation-in-staphylococcus-aureus
#15
Ting Pang, Xindan Wang, Hoong Chuin Lim, Thomas G Bernhardt, David Z Rudner
Successive division events in the spherically shaped bacterium Staphylococcus aureus are oriented in three alternating perpendicular planes. The mechanisms that underlie this relatively unique pattern of division and coordinate it with chromosome segregation remain largely unknown. Thus far, the only known spatial regulator of division in this organism is the nucleoid occlusion protein Noc that inhibits assembly of the cytokinetic ring over the chromosome. However, Noc is not essential in S. aureus, indicating that additional regulators are likely to exist...
July 19, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28723748/clinical-characteristics-and-mutation-spectrum-of-gla-in-korean-patients-with-fabry-disease-by-a-nationwide-survey-underdiagnosis-of-late-onset-phenotype
#16
Jin-Ho Choi, Beom Hee Lee, Sun Hee Heo, Gu-Hwan Kim, Yoo-Mi Kim, Dae-Seong Kim, Jung Min Ko, Young Bae Sohn, Yong Hee Hong, Dong-Hwan Lee, Hoon Kook, Han Hyuk Lim, Kyung Hee Kim, Woo-Shik Kim, Geu-Ru Hong, Su-Hyun Kim, Sang Hyun Park, Chan-Duck Kim, So Mi Kim, Jeong-Sook Seo, Han-Wook Yoo
Fabry disease is a rare X-linked lysosomal storage disorder caused by an α-galactosidase A deficiency. The progressive accumulation of globotriaosylceramide (GL-3) results in life-threatening complications, including renal, cardiac, and cerebrovascular diseases. This study investigated the phenotypic and molecular spectra of GLA mutations in Korean patients with Fabry disease using a nationwide survey.This study included 94 patients from 46 independent pedigrees: 38 adult males, 46 symptomatic females, and 10 pediatric males...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28723685/downregulation-of-macrophage-derived-t-ucr-uc-306-associates-with-poor-prognosis-in-hepatocellular-carcinoma
#17
Hong-Lin Luo, Jie Chen, Tao Luo, Fei-Xiang Wu, Jun-Jie Liu, Hui-Feng Wang, Miao Chen, Le-Qun Li, Hang Li
BACKGROUND/AIMS: Increasing evidence suggests that T-UCRs are involved in the development of cancer. In this study, we evaluated the role of a macrophage-derived T-UCR, uc.306, in the prognosis of hepatitis B (HBV)-related hepatocellular carcinoma (HCC). METHODS: The uc.306 was obtained by screening microassay data obtained during the polarization of U937 cells from the M2 to M1 phenotype. Uc.306 and macrophage molecule markers were detected by qPCR. Immunohistochemical (IHC) assays were used to examine the M1/M2 status of 90 paired HCC tissues...
July 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28721015/cell-and-small-animal-models-for-phenotypic-drug-discovery
#18
REVIEW
Mihaly Szabo, Sara Svensson Akusjärvi, Ankur Saxena, Jianping Liu, Gayathri Chandrasekar, Satish S Kitambi
The phenotype-based drug discovery (PDD) approach is re-emerging as an alternative platform for drug discovery. This review provides an overview of the various model systems and technical advances in imaging and image analyses that strengthen the PDD platform. In PDD screens, compounds of therapeutic value are identified based on the phenotypic perturbations produced irrespective of target(s) or mechanism of action. In this article, examples of phenotypic changes that can be detected and quantified with relative ease in a cell-based setup are discussed...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28720810/biofilm-formation-in-enterococci-genotype-phenotype-correlations-and-inhibition-by-vancomycin
#19
Yomna A Hashem, Heba M Amin, Tamer M Essam, Aymen S Yassin, Ramy K Aziz
Enterococci are nosocomial pathogens that can form biofilms, which contribute to their virulence and antibiotic resistance. Although many genes involved in biofilm formation have been defined, their distribution among enterococci has not been comprehensively studied on a genome scale, and their diagnostic ability to predict biofilm phenotypes is not fully established. Here, we assessed the biofilm-forming ability of 90 enterococcal clinical isolates. Major patterns of virulence gene distribution in enterococcal genomes were identified, and the differentiating virulence genes were screened by polymerase chain reaction (PCR) in 31 of the clinical isolates...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28718813/suppression-of-nrf2-activity-by-chestnut-leaf-extract-increases-chemosensitivity-of-breast-cancer-stem-cells-to-paclitaxel
#20
Yaejin Woo, Jisun Oh, Jong-Sang Kim
Due to metastatic potential and drug resistance, cancer stem cells (CSCs) have become a critical target for the development of chemotherapeutic agents. Recent studies showed that CSCs highly express NF-E2-related factor 2 (Nrf2)-mediated antioxidant enzymes and thereby retain relatively low levels of reactive oxygen species (ROS). Since anticancer agents usually utilize ROS as an arsenal for killing cancer cells, we hypothesized that inhibition of Nrf2 activity could increase the sensitivity of CSCs to anticancer drugs, and thus enhancing their therapeutic efficacy...
July 18, 2017: Nutrients
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