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PubMed Journals Articles About "Locus Discovery Incorporated" - Page: 4 RSS

07:37 EST 15th December 2018 | BioPortfolio

Locus Discovery Incorporated PubMed articles on BioPortfolio. Our PubMed references draw on over 21 million records from the medical literature. Here you can see the latest Locus Discovery Incorporated articles that have been published worldwide.

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Showing "Locus Discovery Incorporated" PubMed Articles 76–100 of 3,000+

Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations.

The selective pressures that shape clonal evolution in healthy individuals are largely unknown. Here we investigate 8,342 mosaic chromosomal alterations, from 50 kb to 249 Mb long, that we uncovered in blood-derived DNA from 151,202 UK Biobank participants using phase-based computational techniques (estimated false discovery rate, 6-9%). We found six loci at which inherited variants associated strongly with the acquisition of deletions or loss of heterozygosity in cis. At three such loci (MPL, TM2D3-TARSL...


Polycyclic Sulfoximines as New Scaffolds for Drug Discovery.

The design and synthesis of three novel and original polycyclic scaffolds containing sulfoximines is presented in this work, showing that sulfoximines represent a real opportunity for the discovery of new drug candidates. Additionally, the structures present at least two points of diversification and contain a high level of sp3-character, hence being very interesting 3D-scaffolds. The compounds synthesized were added to the compound collection of the European Lead Factory.

The essentiality of drug targets: an analysis of current literature and genomic databases.

Essential genes encode proteins thought to be crucial for the survival of an organism. However, the role of essential genes in human disease and their suitability as drug targets is less clear. Here, we use a recent catalog of nearly 9000 known essential and nonessential genes to evaluate their involvement as therapeutic targets in human diseases. We find that essential genes are more likely than nonessential genes to play a part in specific therapeutic areas such as cardiovascular diseases and neoplasms. W...


Frozen in Time: A History of the Synthesis of Nitrous Oxide and How the Process Remained Unchanged for Over 2 Centuries.

Three major factors have contributed to the unrivaled popularity of nitrous oxide (N2O) among anesthetists in the 20th century and beyond: its impressive safety profile, its affordability, and its rapid induction and emergence times. These 3 characteristics of N2O have been discussed and written about extensively throughout the medical literature. Nonetheless, the characteristic that contributed most to N2O's initial discovery-the elegance and simplicity of its synthesis-has received substantially less atte...

Different loci associated with root and foliar resistance to sudden death syndrome (Fusarium virguliforme) in soybean.

Different loci associated with root resistance to F. virguliforme colonization and foliar resistance to phytotoxin damage in soybean. Use of resistant cultivars is the most efficacious approach to manage soybean sudden death syndrome (SDS), caused by Fusarium virguliforme. The objectives of this study were to (1) map the loci associated with root and foliar resistance to F. virguliforme infection and (2) decipher the relationships between root infection, foliar damage, and plot yield. A mapping population c...

Decaprenyl-phosphoryl-ribose 2'-epimerase (DprE1): challenging target for antitubercular drug discovery.

Tuberculosis has proved harmful to the entire history of mankind from past several decades. Decaprenyl-phosphoryl-ribose 2'-epimerase (DprE1) is a recent target which was identified in 2009 but unfortunately it is neither explored nor crossed phase II. In past several decades few targets were identified for effective antitubercular drug discovery. Resistance is the major problem for effective antitubercular drug discovery. Arabinose is constituent of mycobacterium cell wall. Biosynthesis of arabinose is FAD...

Fine mapping and candidate gene screening of the downy mildew resistance gene RPF1 in Spinach.

A SLAF-BSA approach was used to locate the RPF1 locus. The three most likely candidate genes were identified which provide a basic for cloning the resistance gene at the RPF1 locus. Spinach downy mildew is a globally devastating oomycete disease. The use of downy mildew resistance genes constitutes the most effective approach for disease management. Hence, the objective of the present study was to fine map the first-reported resistance locus RPF1. The resistance allele at this resistance locus was effective...

Early Stage Discovery and Validation of Pharmacological Chaperones for the Correction of Protein Misfolding Diseases.

Pharmacological chaperones are small molecular weight molecules that bind specifically to protein targets and stabilize unstable and misfolded conformations. In particular, there is an increasing interest in the application of this type of compounds for the correction of genetic conformational disorders, which are caused by mutations leading to protein instability. The discovery of compounds with pharmacological chaperone ability is customarily initiated by a high-throughput screening of chemical libraries ...

CSBFinder: Discovery of colinear syntenic blocks across thousands of prokaryotic genomes.

Identification of conserved syntenic blocks across microbial genomes is important for several problems in comparative genomics such as gene annotation, study of genome organization and evolution, and prediction of gene interactions. Current tools for syntenic block discovery do not scale up to the large quantity of prokaryotic genomes available today.

Expression and contribution to virulence of each polysaccharide capsule of Bacillus cereus strain G9241.

Bacillus cereus strain G9241 was isolated from a patient with pneumonia who had an anthrax-like illness. Like Bacillus anthracis, the virulence of G9241 is dependent on two large plasmids. In G9241 those plasmids are pBCXO1 and pBC210. There is a multi-gene capsule locus on each of these virulence plasmids, and both capsules are produced by G9241 in vitro and in mice. The hasACB operon on pBCXO1 is responsible for production of a hyaluronic acid (HA) capsule. The locus on pBC210 encodes a putative tetrasacc...

New Developments and Future Directions in Understanding Locus Coeruleus - Norepinephrine (LC-NE) Function.

Machine learning in chemoinformatics and drug discovery.

Chemoinformatics is an established discipline focusing on extracting, processing and extrapolating meaningful data from chemical structures. With the rapid explosion of chemical 'big' data from HTS and combinatorial synthesis, machine learning has become an indispensable tool for drug designers to mine chemical information from large compound databases to design drugs with important biological properties. To process the chemical data, we first reviewed multiple processing layers in the chemoinformatics pipe...

The brain of the tree pangolin (Manis tricuspis). III. The unusual locus coeruleus complex.

Here we employed a range of immunohistochemical stains, focussing on tyrosine hydroxylase and dopamine-β-hydroxylase, to show that within the pons of tree pangolins clusters of noradrenergic neurons are present. No noradrenergic neurons were observed in the pontine periventricular grey matter (A6 and A4 groups missing), with all noradrenergic neurons being found within the pontine tegmentum (A7 and A5 groups). The tree pangolin is unique in lacking the locus coeruleus (A6) cell group observed in all verteb...

Discovery of multi-megabase polymorphic inversions by chromosome conformation capture sequencing in large-genome plant species.

Chromosomal inversions occur in natural populations of many species and may underlie reproductive isolation and local adaptation. Traditional methods of inversion discovery are labor-intensive and lack sensitivity. Here, we report the use of three-dimensional contact probabilities between genomic loci as assayed by chromosome conformation capture sequencing (Hi-C) to detect multi-megabase polymorphic inversions in four barley genotypes. Inversions are validated by fluorescence in situ hybridization and Bion...

Zinc finger nuclease-mediated targeting of multiple transgenes to an endogenous soybean genomic locus via non-homologous end joining.

Emerging genome editing technologies hold great promise for the improvement of agricultural crops. Several related genome editing methods currently in development utilize engineered, sequence-specific endonucleases to generate DNA double strand breaks (DSBs) at user-specified genomic loci. These DSBs subsequently result in small insertions/deletions (indels), base substitutions, or incorporation of exogenous donor sequences at the target site, depending on the application. Targeted mutagenesis in soybean (G...

Multi-locus sequence typing as a tool to investigate environmental sources of infection for cryptococcosis in captive birds.

A systematic investigation into environmental sources of infection was conducted at an Australian zoological park after cryptococcosis, caused by Cryptococcus gattii VGI, was diagnosed in a red-tailed black cockatoo (Calyptorhynchus banksii) residing in a large aviary with a diverse range of other avian species. A single tree with an extensive hollow was identified as the likely source of infection based on heavy culture of C. gattii VGI, multi-locus sequence typing and phylogenetic analysis of environmenta...

Unequal distribution of the mating type (MAT) locus idiomorphs in dermatophyte species.

Importance of target-mediated drug disposition for small molecules.

Target concentration is typically not considered in drug discovery. However, if targets are expressed at relatively high concentrations and compounds have high affinity, such that most of the drug is bound to its target, in vitro screens can give unreliable information on compound affinity. In vivo, a similar situation will generate pharmacokinetic (PK) profiles that deviate greatly from those normally expected, owing to target binding affecting drug distribution and clearance. Such target-mediated drug dis...

Small-molecule inhibitors of macrophage migration inhibitory factor (MIF) as an emerging class of therapeutics for immune disorders.

Macrophage migration inhibitory factor (MIF) is an important cytokine for which an increasing number of functions is being described in the pathogenesis of inflammation and cancer. Nevertheless, the availability of potent and druglike MIF inhibitors that are well-characterized in relevant disease models remains limited. Highly potent and selective small-molecule MIF inhibitors and validation of their use in relevant disease models will advance drug discovery. In this review, we provide an overview of recent...

Computational Methods and Tools to Predict Cytochrome P450 Metabolism for Drug Discovery.

In this review we present important, recent developments in the computational prediction of cytochrome P450 (CYP) metabolism in the context of drug discovery. We discuss in silico models for the various aspects of CYP metabolism prediction, including CYP substrate and inhibitor predictors, site of metabolism predictors (i.e. metabolically labile sites within potential substrates) and metabolite structure predictors. We summarise the different approaches taken by these models, such as rule-based methods, mac...

Discovery of a novel species, Theileria haneyi n. sp., infective to equids, highlights exceptional genomic diversity within the genus Theileria: implications for apicomplexan parasite surveillance.

A novel apicomplexan parasite was serendipitously discovered in horses at the United States - Mexico border. Phylogenetic analysis based on 18S rDNA showed the erythrocyte-infective parasite to be related to, but distinct from, Theileria spp. in Africa, the most similar taxa being Theileria spp. from waterbuck and mountain zebra. The degree of sequence variability observed at the 18S rDNA locus also suggests the likely existence of additional cryptic species. Among described species, the genome of this nove...

Proteomic approaches for novel systemic lupus erythematosus (SLE) drug discovery.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a high risk of morbidity and mortality; however, there is no cure and the current medications are far from optimal in addressing efficacy and safety concerns. Over the past decade, various emerging technologies have been used in the search for novel drug targets of SLE which have resulted in numerous promising data. However, the systematic review and careful digestion of this information have been lacking. Areas covered: In this review,...

Epilepsy-on-a-chip System for Antiepileptic Drug Discovery.

Hippocampal slice cultures spontaneously develop chronic epilepsy several days after slicing and are used as an in vitro model of post-traumatic epilepsy. Here, we describe a hybrid microfluidic-microelectrode array (μflow-MEA) technology that incorporates microfluidic perfusion network and electrodes into a miniaturized device for hippocampal slice culture based antiepileptic drug discovery.

Interaction between plasma homocysteine and the MTHFR c.677C > T polymorphism is associated with site-specific changes in DNA methylation in humans.

One-carbon metabolism provides a direct link among dietary folate/vitamin B exposure, the activity of the enzyme methylenetetrahydrofolate reductase (MTHFR), and epigenetic regulation of the genome via DNA methylation. Previously, it has been shown that the common c.677C > T polymorphism in MTHFR influences global DNA methylation status through a direct interaction with folate status and (indirectly) with total homocysteine (tHcy) levels. To build on that and other more-recent observations that have further...

Microtransplantation of human brain receptors into oocytes to tackle key questions in drug discovery.

It is important in drug discovery to demonstrate that activity of novel drugs found by screening on recombinant receptors translates to activity on native human receptors in brain areas affected by disease. In this review, we summarise the development and use of the microtransplantation technique. Native receptors are reconstituted from human brain tissues into oocytes from the frog Xenopus laevis where they can be functionally assessed. Oocytes microtransplanted with hippocampal tissue from an epileptic pa...


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