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

11:30 EDT 22nd October 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 2,900+

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.

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...


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...

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...

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.

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...

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.

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...

Discovery of traditional Chinese medicine monomers and their synthetic intermediates, analogs or derivatives for battling P-gp-mediated multi-drug resistance.

P-glycoprotein (P-gp)-mediated multi-drug resistance (MDR) is a well-documented and predominant phenotype hampering patients' response to cancer chemotherapy. Although the past several decades have witnessed the development of three generations of P-gp inhibitors, they have not lived up to the high expectations owing to their drawbacks, as exemplified by limited efficacy, drug-drug interactions (DDIs) and severe untoward reactions. The discovery of artemisinin is a testimony of the importance of traditional...

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...

Discovery and Characterization of a High-Affinity Small Peptide Ligand, H1, Targeting FGFR2IIIc for Skin Wound Healing.

How to aid recovery from severe skin injuries, such as burns, chronic or radiation ulcers, and trauma, is a critical clinical problem. Current treatment methods remain limited, and the discovery of ideal wound-healing therapeutics has been a focus of research. Functional recombinant proteins such as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) have been developed for skin repair, however, some disadvantages in their use remain. This study reports the discovery of a novel small pep...

'Tethering' fragment-based drug discovery to identify inhibitors of the essential respiratory membrane protein type II NADH dehydrogenase.

Energy generation is a promising area of drug discovery for both bacterial pathogens and parasites. Type II NADH dehydrogenase (NDH-2), a vital respiratory membrane protein, has attracted attention as a target for the development of new antitubercular and antimalarial agents. To date, however, no potent, specific inhibitors have been identified. Here, we performed a site-directed screening technique, tethering-fragment based drug discovery, against wild-type and mutant forms of NDH-2 containing engineered a...

Real-time imaging of specific genomic loci in eukaryotic cells using the ANCHOR DNA labelling system.

Spatio-temporal organization of the cell nucleus adapts to and regulates genomic processes. Microscopy approaches that enable direct monitoring of specific chromatin sites in single cells and in real time are needed to better understand the dynamics involved. In this chapter, we describe the principle and development of ANCHOR, a novel tool for DNA labelling in eukaryotic cells. Protocols for use of ANCHOR to visualize a single genomic locus in eukaryotic cells are presented. We describe an approach for liv...

Ion Channels in Drug Discovery and Safety Pharmacology.

Ion channels are membrane proteins involved in almost all physiological processes, including neurotransmission, muscle contraction, pace-making activity, secretion, electrolyte and water balance, immune response, and cell proliferation. Due to their broad distribution in human body and physiological roles, ion channels are attractive targets for drug discovery and safety pharmacology. Over the years ion channels have been associated to many genetic diseases ("channelopathies"). For most of these diseases th...

An efficient multi-locus mixed model framework for the detection of small and linked QTLs in F2.

In the genetic system that regulates complex traits, metabolites, gene expression levels, RNA editing levels and DNA methylation, a series of small and linked genes exist. To date, however, little is known about how to design an efficient framework for the detection of these kinds of genes. In this article, we propose a genome-wide composite interval mapping (GCIM) in F2. First, controlling polygenic background via selecting markers in the genome scanning of linkage analysis was replaced by estimating polyg...

MS methods to study macromolecule-ligand interaction: applications in drug discovery.

The interaction of small compounds (i.e. ligands) with macromolecules or macromolecule assemblies (i.e. targets) is the mechanism of action of most of the drugs available today. Mass spectrometry is a popular technique for the interrogation of macromolecule-ligand interactions and therefore is also widely used in drug discovery and development. Thanks to its versatility, mass spectrometry is used for multiple purposes such as biomarker screening, identification of the mechanism of action, ligand structure o...

Genetic study of multimodal imaging Alzheimer's disease progression score implicates novel loci.

Identifying genetic risk factors underpinning different aspects of Alzheimer's disease has the potential to provide important insights into pathogenesis. Moving away from simple case-control definitions, there is considerable interest in using quantitative endophenotypes, such as those derived from imaging as outcome measures. Previous genome-wide association studies of imaging-derived biomarkers in sporadic late-onset Alzheimer's disease focused only on phenotypes derived from single imaging modalities. In...

Streptomyces species: Ideal chassis for natural product discovery and overproduction.

There is considerable interest in mining organisms for new natural products (NPs) and in improving methods to overproduce valuable NPs. Because of the rapid development of tools and strategies for metabolic engineering and the markedly increased knowledge of the biosynthetic pathways and genetics of NP-producing organisms, genome mining and overproduction of NPs can be dramatically accelerated. In particular, Streptomyces species have been proposed as suitable chassis organisms for NP discovery and overprod...

Estrogens and selective estrogen receptor modulators differentially antagonize Runx2 in ST2 mesenchymal progenitor cells.

Estrogens attenuate bone turnover by inhibiting both osteoclasts and osteoblasts, in part through antagonizing Runx2. Apparently conflicting, stimulatory effects in osteoblast lineage cells, however, sway the balance between bone resorption and bone formation in favor of the latter. Consistent with this dualism, 17ß-estradiol (E2) both stimulates and inhibits Runx2 in a locus-specific manner, and here we provide evidence for such locus-specific regulation of Runx2 by E2 in vivo. We also demonstrate dual, n...

Integration of Lead Discovery Tactics and the Evolution of the Lead Discovery Toolbox.

There has been much debate around the success rates of various screening strategies to identify starting points for drug discovery. Although high-throughput target-based and phenotypic screening has been the focus of this debate, techniques such as fragment screening, virtual screening, and DNA-encoded library screening are also increasingly reported as a source of new chemical equity. Here, we provide examples in which integration of more than one screening approach has improved the campaign outcome and di...

Commentary: Locus Coeruleus Ablation Exacerbates Cognitive Deficits, Neuropathology, and Lethality in P301S Tau Transgenic Mice.


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