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https://www.readbyqxmd.com/read/29156751/identification-of-potential-tissue-specific-cancer-biomarkers-and-development-of-cancer-versus-normal-genomic-classifiers
#1
Akram Mohammed, Greyson Biegert, Jiri Adamec, Tomáš Helikar
Machine learning techniques for cancer prediction and biomarker discovery can hasten cancer detection and significantly improve prognosis. Recent "OMICS" studies which include a variety of cancer and normal tissue samples along with machine learning approaches have the potential to further accelerate such discovery. To demonstrate this potential, 2,175 gene expression samples from nine tissue types were obtained to identify gene sets whose expression is characteristic of each cancer class. Using random forests classification and ten-fold cross-validation, we developed nine single-tissue classifiers, two multi-tissue cancer-versus-normal classifiers, and one multi-tissue normal classifier...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156672/discovery-of-spermatogenic-activators-a-lesson-from-bone-morphogenetic-protein-8
#2
EDITORIAL
Fang-Ju Wu, Ching-Wei Luo
No abstract text is available yet for this article.
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156643/melanoma-genetic-abnormalities-tumor-progression-clonal-evolution-and-tumor-initiating-cells
#3
REVIEW
Ugo Testa, Germana Castelli, Elvira Pelosi
Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future...
November 20, 2017: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29156600/fabrication-of-semiconductor-zno-nanostructures-for-versatile-sers-application
#4
REVIEW
Lili Yang, Yong Yang, Yunfeng Ma, Shuai Li, Yuquan Wei, Zhengren Huang, Nguyen Viet Long
Since the initial discovery of surface-enhanced Raman scattering (SERS) in the 1970s, it has exhibited a huge potential application in many fields due to its outstanding advantages. Since the ultra-sensitive noble metallic nanostructures have increasingly exposed themselves as having some problems during application, semiconductors have been gradually exploited as one of the critical SERS substrate materials due to their distinctive advantages when compared with noble metals. ZnO is one of the most representative metallic oxide semiconductors with an abundant reserve, various and cost-effective fabrication techniques, as well as special physical and chemical properties...
November 19, 2017: Nanomaterials
https://www.readbyqxmd.com/read/29156457/discovery-of-novel-thiazol-2-amines-and-their-analogues-as-bioactive-molecules-design-synthesis-docking-and-biological-evaluation
#5
Anil Kumar Verma, Abha Bishnoi, Shaheen Fatma, Huda Parveen, Vineeta Singh
A simple and highly efficient procedure for the synthesis of novel thiazol-2-amines, via Mannich reaction with secondary amines, is described. The newly synthesized derivatives 8(a-e) and 9(a-e) were characterized by (1)H NMR, (13)C NMR, IR, Mass spectroscopy and elemental analysis. All the derivatives were evaluated for their in-vitro anti-microbial activity against a panel of pathogenic strains of bacteria and fungi. The SAR showed that the secondary amines had a significant impact on the in-vitro antimicrobial activity of this class of agents...
November 20, 2017: Drug Research
https://www.readbyqxmd.com/read/29156442/charting-a-path-towards-non-destructive-biomarkers-in-threatened-wildlife-a-systematic-quantitative-literature-review
#6
REVIEW
Stephanie Chaousis, Frederic D L Leusch, Jason P van de Merwe
Threatened species are susceptible to irreversible population decline caused by adverse sub-lethal effects of chemical contaminant exposure. It is therefore vital to develop the necessary tools to predict and detect these effects as early as possible. Biomarkers of contaminant exposure and effect are widely applied to this end, and a significant amount of research has focused on development and validation of sensitive and diagnostic biomarkers. However, progress in the use biomarkers that can be measured using non-destructive techniques has been relatively slow and there are still many difficulties to overcome in the development of sound methods...
November 17, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29156384/targeting-fgfr-pathway-in-breast-cancer
#7
J Perez-Garcia, E Muñoz-Couselo, J Soberino, F Racca, J Cortes
Developments in breast cancer biology over the last years have permitted deconstructing the molecular profile of the most relevant breast cancer subtypes. This has led to an increase in therapeutic options, including more effective personalized therapy for breast cancer and substantial improvements in patient outcomes. Although currently there are only a few targeted therapies approved for metastatic breast cancer, the discovery of druggable kinase gene alterations has radically changed cancer treatment by providing novel and successfully actionable drug targets...
November 17, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29156382/discovery-of-selective-dengue-virus-inhibitors-using-combination-of-molecular-fingerprint-based-virtual-screening-protocols-structure-based-pharmacophore-model-development-molecular-dynamics-simulations-and-in-vitro-studies
#8
Shaher Bano Mirza, Regina Ching Hua Lee, Justin Jang Hann Chu, Ramin Ekhteiari Salmas, Thomas Mavromoustakos, Serdar Durdagi
Dengue virus is a major issue of tropical and sub-tropical regions. The proliferation of virus results in immense number of deaths each year because of unavailability of on-shelf drugs. This issue necessitates the design of novel anti-Dengue drugs. The protease enzyme pathway is the critical target for drug design due to its significance in the replication, survival and other cellular activities of Dengue virus. Keeping in mind the worsening situation regarding Dengue virus, approximately eighteen million drug-like compounds from the ZINC small molecule database have been screened against Nonstructural Protein 3 (NS3) previously by our group...
October 24, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29156309/recent-development-of-computational-resources-for-new-antibiotics-discovery
#9
REVIEW
Hyun Uk Kim, Kai Blin, Sang Yup Lee, Tilmann Weber
Understanding a complex working mechanism of biosynthetic gene clusters (BGCs) encoding secondary metabolites is a key to discovery of new antibiotics. Computational resources continue to be developed in order to better process increasing volumes of genome and chemistry data, and thereby better understand BGCs. In this context, this review highlights recent advances in computational resources for secondary metabolites with emphasis on genome mining, compound identification and dereplication as well as databases...
November 16, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29156234/candida-albicans-epithelial-interactions-and-induction-of-mucosal-innate-immunity
#10
REVIEW
Julian R Naglik, Annika König, Bernhard Hube, Sarah L Gaffen
Candida albicans is a human fungal pathogen that causes millions of mucosal and life-threatening infections annually. C. albicans initially interacts with epithelial cells, resulting in fungal recognition and the formation of hyphae. Hypha formation is critical for host cell damage and immune activation, which are both driven by the secretion of Candidalysin, a recently discovered peptide toxin. Epithelial activation leads to the production of inflammatory mediators that recruit innate immune cells including neutrophils, macrophages and innate Type 17 cells, which together work with epithelial cells to clear the fungal infection...
November 17, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29156207/intracellular-protein-degradation-from-a-vague-idea-thru-the-lysosome-and-the-ubiquitin-proteasome-system-and-onto-human-diseases-and-drug-targeting
#11
REVIEW
Aaron Ciechanover
Between the 1950s and 1980s, scientists were focusing mostly on how the genetic code is transcribed to RNA and translated to proteins, but how proteins are degraded has remained a neglected research area. With the discovery of the lysosome by Christian de Duve it was assumed that cellular proteins are degraded within this organelle. Yet, several independent lines of experimental evidence strongly suggested that intracellular proteolysis is largely non-lysosomal, but the mechanisms involved remained obscure...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29156136/the-discovery-of-3-4-chloro-3-methoxyphenyl-amino-1-3r-4s-4-cyanotetrahydro-2h-pyran-3-yl-1h-pyrazole-4-carboxamide-a-highly-ligand-efficient-and-efficacious-jak1-selective-inhibitor-with-favorable-pharmacokinetic-properties
#12
Tony Siu, Jason Brubaker, Peter Fuller, Luis Torres, Hongbo Zeng, Joshua Close, Dawn M Mampreian, Feng Shi, Duan Liu, Xavier Fradera, Kevin Johnson, Nathan Bays, Elma Kadic, Fang He, Peter Goldenblatt, Lynsey Shaffer, Sangita B Patel, Charles A Lesburg, Carla Alpert, Lauren Dorosh, Sujal V Deskmukh, Hongshi Yu, Joel Klappenbach, Fiona Elwood, Christopher J Dinsmore, Rafael Fernandez, Lily Moy, Jonathan R Young
The discovery of a potent selective low dose JAK1 inhibitor suitable for clinical evaluation is described. As part of an overall goal to minimize dose, we pursued a medicinal chemistry strategy focused on optimization of key parameters that influence dose size, including lowering human Clint and increasing intrinsic potency, bioavailability, and solubility. To impact these multiple parameters simultaneously, we used lipophilic ligand efficiency as a key metric to track changes in the physicochemical properties of our analogs, which led to improvements in overall compound quality...
November 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29156055/analysis-of-an-adtkd-family-with-a-novel-frameshift-mutation-in-muc1-reveals-characteristic-features-of-mutant-muc1-protein
#13
Satoko Yamamoto, Jun-Ya Kaimori, Takuji Yoshimura, Tomoko Namba, Atsuko Imai, Kaori Kobayashi, Ryoichi Imamura, Naotsugu Ichimaru, Kazuto Kato, Akihiro Nakaya, Shiro Takahara, Yoshitaka Isaka
Background: Medullary cystic kidney disease Type 1 is an autosomal dominant tubulointerstitial kidney disease (ADTKD). Recently, mucin 1 ( MUC1 ) was identified as a causal gene of medullary cystic kidney disease (ADTKD-MUC1). However, the MUC1 mutation was found to be a single cytosine insertion in a single copy of the GC-rich variable number of tandem repeats (VNTRs), which are very difficult to analyze by next-generation sequencing. To date, other mutations have not been detected in ADTKD-MUC1, and the mutant MUC1 protein has not been analyzed because of the difficulty of genetically modifying the VNTR sequence...
June 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29155974/transcript-profiling-of-a-bitter-variety-of-narrow-leafed-lupin-to-discover-alkaloid-biosynthetic-genes
#14
Ting Yang, Istvan Nagy, Davide Mancinotti, Sophie Lisa Otterbach, Trine Bundgaard Andersen, Mohammed Saddik Motawia, Torben Asp, Fernando Geu-Flores
Lupins (Lupinus spp.) are nitrogen-fixing legumes that accumulate toxic alkaloids in their protein-rich beans. These anti-nutritional compounds belong to the family of quinolizidine alkaloids (QAs), which are of interest to the pharmaceutical and chemical industries. To unleash the potential of lupins as protein crops and as sources of QAs, a thorough understanding of the QA pathway is needed. However, only the first enzyme in the pathway, lysine decarboxylase (LDC), is known. Here, we report the transcriptome of a high-QA variety of narrow-leafed lupin (L...
November 16, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29155959/the-discovery-potential-of-rna-processing-profiles
#15
Amadís Pagès, Ivan Dotu, Joan Pallarès-Albanell, Eulàlia Martí, Roderic Guigó, Eduardo Eyras
Small non-coding RNAs (sncRNAs) are highly abundant molecules that regulate essential cellular processes and are classified according to sequence and structure. Here we argue that read profiles from size-selected RNA sequencing capture the post-transcriptional processing specific to each RNA family, thereby providing functional information independently of sequence and structure. We developed SeRPeNT, a new computational method that exploits reproducibility across replicates and uses dynamic time-warping and density-based clustering algorithms to identify, characterize and compare sncRNAs by harnessing the power of read profiles...
November 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29155944/molecular-interaction-search-tool-mist-an-integrated-resource-for-mining-gene-and-protein-interaction-data
#16
Yanhui Hu, Arunachalam Vinayagam, Ankita Nand, Aram Comjean, Verena Chung, Tong Hao, Stephanie E Mohr, Norbert Perrimon
Model organism and human databases are rich with information about genetic and physical interactions. These data can be used to interpret and guide the analysis of results from new studies and develop new hypotheses. Here, we report the development of the Molecular Interaction Search Tool (MIST; http://fgrtools.hms.harvard.edu/MIST/). The MIST database integrates biological interaction data from yeast, nematode, fly, zebrafish, frog, rat and mouse model systems, as well as human. For individual or short gene lists, the MIST user interface can be used to identify interacting partners based on protein-protein and genetic interaction (GI) data from the species of interest as well as inferred interactions, known as interologs, and to view a corresponding network...
November 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29155663/frameworks-for-preventing-detecting-and-controlling-zoonotic-diseases
#17
Miriam L Shiferaw, Jeffrey B Doty, Giorgi Maghlakelidze, Juliette Morgan, Ekaterine Khmaladze, Otar Parkadze, Marina Donduashvili, Emile Okitolonda Wemakoy, Jean-Jacques Muyembe, Leopold Mulumba, Jean Malekani, Joelle Kabamba, Theresa Kanter, Linda Lucy Boulanger, Abraham Haile, Abyot Bekele, Meseret Bekele, Kasahun Tafese, Andrea A McCollum, Mary G Reynolds
Preventing zoonotic diseases requires coordinated actions by government authorities responsible for human and animal health. Constructing the frameworks needed to foster intersectoral collaboration can be approached in many ways. We highlight 3 examples of approaches to implement zoonotic disease prevention and control programs. The first, rabies control in Ethiopia, was implemented using an umbrella approach: a comprehensive program designed for accelerated impact. The second, a monkeypox program in Democratic Republic of the Congo, was implemented in a stepwise manner, whereby incremental improvements and activities were incorporated into the program...
December 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/29155568/discovery-of-a-novel-series-of-tankyrase-inhibitors-by-a-hybridization-approach
#18
Upendra Rao Anumala, Jo Waaler, Yves Nkizinkiko, Alexander Ignatev, Katina Lazarow, Peter Lindemann, Petter Angell Olsen, Sudarshan Murthy, Ezeogo Obaji, Alexander G Majouga, Sergey V Leonov, Jens Peter von Kries, Lari Lehtiö, Stefan Krauss, Marc Nazaré
A structure-guided hybridization approach using two privileged substructures gave instant access to a new series of tankyrase inhibitors. The identified inhibitor 16 displays high target affinity on tankyrase 1 and 2 with a biochemical and cellular IC50 values of 29 nM, 6.3 nM and 19 nM, respectively, and high selectivity towards other Poly(ADP-ribose) polymerase enzymes. The identified inhibitor shows a favorable in-vitro ADME profile as well as good oral bioavailability in mice, rats and dogs. Critical for the approach was the utilization of an appropriate linker between 1,2,4-triazole and benzimidazolone moieties, whereby a cyclobutyl linker displayed superior affinity compared to a cyclohexane and phenyl linker...
November 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29155559/crafting-of-neuroprotective-octapeptide-from-taxol-binding-pocket-of-%C3%AE-tubulin
#19
Prasenjit Mondal, Gaurav Das, Juhee Khan, Krishnangsu Pradhan, Surajit Ghosh
Microtubules play crucial role in maintaining the shape and function of neurons. During progression of Alzheimer's disease (AD), severe destabilization of microtubule occurs, which leads to the permanent disruption of signal transduction process and memory loss. Thus, microtubule stabilization is one of the key requirements for the treatment of AD. Taxol, a microtubule stabilizing anti-cancer drug has been considered as potential anti-AD drug but never tested in AD patients, likely because of its' toxic nature and poor brain exposure...
November 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29155484/elevated-difenacoum-metabolism-involved-in-the-difenacoum-resistant-phenotype-observed-in-berkshire-rats-homozygous-for-the-l120q-mutation-in-vkorc1-gene
#20
Maylis Boitet, Abdessalem Hammed, Nolan Chatron, Jean Valéry Debaux, Etienne Benoit, Virginie Lattard
BACKGROUND: After its initial use, resistance to difenacoum has been detected rapidly in rats in north-east Hampshire and north-west Berkshire in England. Resistance to difenacoum has been reported to be stronger in rats from Berkshire than rats from Hampshire. Surprisingly, after the discovery of the Vkorc1 gene, rats from Berkshire and Hampshire were all shown to be homozygous for the L120Q mutation in the Vkorc1. RESULTS: This study aims to evaluate the resistance of Berkshire rats to confirm their extreme resistance and determine mechanisms supporting this resistance...
November 20, 2017: Pest Management Science
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