Discovery of -quinazolinone-4-hydroxy-2-quinolone-3-carboxamides as DNA gyrase B-targeted antibacterial agents.

Emerging drug resistance is generating an urgent need for novel and effective antibiotics. A promising target that has not yet been addressed by approved antibiotics is the bacterial DNA gyrase subunit B (GyrB), and GyrB inhibitors could be effective against drug-resistant bacteria, such as methicillin-resistant (MRSA). Here, we used the 4-hydroxy-2-quinolone fragment to search the Specs database of purchasable compounds for potential inhibitors of GyrB and identified or , as a novel and potent inhibitor of the target protein (IC: 1.

Structure-guided optimization of D-captopril for discovery of potent NDM-1 inhibitors.

β-lactam antibiotics have long been the mainstay for the treatment of bacterial infections. New Delhi metallo-β-lactamase 1 (NDM-1) is able to hydrolyze nearly all β-lactam antibiotics and even clinically used serine-β-lactamase inhibitors. The wide and rapid spreading of NDM-1 gene among pathogenic bacteria has attracted extensive attention, therefore high potency NDM-1 inhibitors are urgently needed.

Influence of sampling rate on voice analysis for assessment of Parkinson's disease.

Parkinson's diagnosis through voice analysis (PDVA) has been attracting increasing attention. In this paper, the influence of sampling rate on PDVA is studied. By analyzing the main difficulties that hamper the development of PDVA, the significance of seeking guidelines on sampling rate is discussed.

[Sn-glycerol-3-phosphate acyltransferases (GPATs) in plants].

Sn-glycerol-3-phosphate acyltransferase (GPAT) catalyzes the acylation at sn-1 position of glycerol-3-phosphate to produce lysophosphatidic acid (LPA) in an acyl-CoA or acyl-ACP-dependent manner, which is the initial and rate-determining step of TAG biosynthetic pathway. Some GPATs have sn-2 transfer activity. Part members of the GPAT gene family have been cloned from different plant species.

Agonists of the orphan human G2A receptor identified from inducible G2A expression and beta-lactamase reporter screen.

The G protein-coupled receptor (GPCR) G2A (for G2 accumulation) was identified as a stress-inducible antiproliferative cell cycle regulator. Targeted G2A gene deletion in mice resulted in systemic lupus erythematosus-like and atherosclerotic lesion phenotypes. These findings suggested that G2A may be a therapeutic target for cancers and autoimmune and cardiovascular diseases.

Revisiting nestin expression in retinal progenitor cells in vitro and after transplantation in vivo.

The purpose of this study is to characterize the co-expression of nestin--a neuroectodermal stem cell and a reactive glial marker-with various mature retinal cell markers in retinal progenitor cells (RPCs) expanded in vitro, followed either by in vitro induction or subretinal transplantation. Rat RPCs derived from embryonic day (E) 17 rat retina were expanded in serum free defined culture, and induced to differentiate by all-trans retinoic acid (RA). Following induction, cells were stained for nestin in combination with retinal neuronal and glial markers.

Carboxypeptidase E is required for normal synaptic transmission from photoreceptors to the inner retina.

Defects in the gene encoding carboxypeptidase E (CPE) in either mouse or human lead to multiple endocrine disorders, including obesity and diabetes. Recent studies on Cpe-/- mice indicated neurological deficits in these animals. As a model system to study the potential role of CPE in neurophysiology, we carried out electroretinography (ERG) and retinal morphological studies on Cpe-/- and Cpe fat/fat mutant mice.

The 5' flanking sequence of the human retGC1 gene acquires a photoreceptor cell restricted activity pattern over the course of retinal development.

Purpose: Specific mutations of the retinal guanylyl cyclase-1 (retGC1) gene have been linked to Leber congenital amaurosis type 1 (LCA1) and cone-rod dystrophies in humans, diseases that are amenable to treatments using molecular based therapies. As a step towards developing a therapeutic transgene for LCA1, we analyzed the cell specific and developmental activity profiles of fragments of the human retGC1 5' flanking region in vivo.

Methods: We generated self inactivating lentiviral vector constructs carrying three different fragments of the human retGC1 promoter fused to a nuclear localized beta-galactosidase reporter gene (nlacZ).

Transcriptional regulation of aromatase expression in human breast tissue.

Aromatase (CYP19) is the estrogen synthetase that converts androgen to estrogen. The expression of aromatase in breast cancer cells and surrounding stromal cells is up regulated compared to non-cancerous cells. In situ estrogen synthesis is thought to stimulate breast cancer growth in both an autocrine and a paracrine manner.