Identification and characterization of zinc importers in .

is the causative agent of diphtheria, a severe respiratory disease in humans. colonizes the human upper respiratory tract, where it acquires zinc, an essential metal required for survival in the host. While the mechanisms for zinc transport by are not well characterized, four putative zinc ABC-type transporter loci were recently identified in strain 1737: (), (), (), and ().

The Relationship Between Height and Income With Potential Application to Treatment of Limb Length Discrepancy.

Purpose When treating limb length discrepancy (LLD), decisions regarding lengthening versus contralateral shortening require careful consideration of deformity and patient factors. Using the National Longitudinal Survey of Youth 1979 (NLSY79) database, and income as a quantitative representation of overall socioeconomic benefit, we sought to determine the height at which incremental gains in height have the greatest value. Methods Using the NLSY79 database, we collected demographic data, height, yearly income from wages, college education (full- or part-time), and receipt of government financial aid.

An evolutionary continuum from nucleated dwarf galaxies to star clusters.

Systematic studies have revealed hundreds of ultra-compact dwarf galaxies (UCDs) in the nearby Universe. With half-light radii r of approximately 10-100 parsecs and stellar masses M≈ 10-10solar masses, UCDs are among the densest known stellar systems. Although similar in appearance to massive globular clusters, the detection of extended stellar envelopes, complex star formation histories, elevated mass-to-light ratio and supermassive black holes suggest that some UCDs are remnant nuclear star clusters of tidally stripped dwarf galaxies, or even ancient compact galaxies.

The Corynebacterium diphtheriae HbpA Hemoglobin-Binding Protein Contains a Domain That Is Critical for Hemoprotein Binding, Cellular Localization, and Function.

The acquisition of hemin iron from hemoglobin-haptoglobin (Hb-Hp) by Corynebacterium diphtheriae requires the iron-regulated surface proteins HtaA, ChtA, and ChtC and the recently identified Hb-Hp-binding protein, HbpA. We previously showed that a purified form of HbpA (HbpA-S), lacking the C-terminal region, was able to bind Hb-Hp. In this study, we show that the C-terminal region of HbpA significantly enhances binding to Hb-Hp.

Analysis of the Manganese and MntR Regulon in Corynebacterium diphtheriae.

Corynebacterium diphtheriae is the causative agent of a severe respiratory disease in humans. The bacterial systems required for infection are poorly understood, but the acquisition of metals such as manganese (Mn) is likely critical for host colonization. MntR is an Mn-dependent transcriptional regulator in C.

Identification of zinc and Zur-regulated genes in Corynebacterium diphtheriae.

Corynebacterium diphtheriae is a Gram-positive bacterial pathogen and the causative agent of diphtheria, a severe disease of the upper respiratory tract of humans. Factors required for C. diphtheriae to survive in the human host are not well defined, but likely include the acquisition of essential metals such as zinc.

Presence and diagnostic value of circulating tsncRNA for ovarian tumor.

tRNA-derived small non-coding RNAs (tsncRNAs), a class of newly defined small non-coding RNA, have been considered to be involved in various cellular biological processes through regulating gene expression at both transcriptional and post-transcriptional level. However, the presence of circulating tsncRNAs and their diagnostic potential is largely unclear. In this study, we investigate the serum-derived public transcriptome data from ovarian tumor patients and non-cancer controls, and find that circulating tsncRNAs cover a high proportion of total small RNA and are non-random degradation products in serum (ranging from 2.

Iron and Zinc Regulate Expression of a Putative ABC Metal Transporter in Corynebacterium diphtheriae.

, a Gram-positive, aerobic bacterium, is the causative agent of diphtheria and cutaneous infections. While mechanisms required for heme iron acquisition are well known in , systems involved in the acquisition of other metals such as zinc and manganese remain poorly characterized. In this study, we identified a genetic region that encodes an ABC-type transporter () and that is flanked by two genes ( and ) encoding putative substrate binding proteins of the cluster 9 family, a related group of transporters associated primarily with the import of Mn and Zn.

Discovery of novel potent HCV NS5B polymerase non-nucleoside inhibitors bearing a fused benzofuran scaffold.

This letter describes the discovery of a fused benzofuran scaffold viable for preparing a series of novel potent HCV NS5B polymerase non-nucleoside inhibitors. Designed on the basis of the functionalized benzofuran derivative nesbuvir (HCV-796), these compounds presumably bind similarly to the allosteric binding site in the "palm" domain of HCV NS5B protein. SAR of each potential hydrogen-bonding interaction site of this novel scaffold is discussed along with some preliminary genotypic profile and PK data of several advanced compounds.

Corynebacterium diphtheriae Iron-Regulated Surface Protein HbpA Is Involved in the Utilization of the Hemoglobin-Haptoglobin Complex as an Iron Source.

utilizes various heme-containing proteins, including hemoglobin (Hb) and the hemoglobin-haptoglobin complex (Hb-Hp), as iron sources during growth in iron-depleted environments. The ability to utilize Hb-Hp as an iron source requires the surface-anchored proteins HtaA and either ChtA or ChtC. The ability to bind hemin, Hb, and Hb-Hp by each of these proteins requires the previously characterized conserved region (CR) domain.

Vibrio cholerae VciB Mediates Iron Reduction.

is the causative agent of the severe diarrheal disease cholera. thrives within the human host, where it replicates to high numbers, but it also persists within the aquatic environments of ocean and brackish water. To survive within these nutritionally diverse environments, must encode the necessary tools to acquire the essential nutrient iron in all forms it may encounter.

Discovery of ravidasvir (PPI-668) as a potent pan-genotypic HCV NS5A inhibitor.

This Letter describes the synthesis, representative structure activity relationship (SAR), activity and PK profiles of a series of functionalized benzimidazole-naphthylene-imidazole derivatives as HCV NS5A inhibitors. This effort successfully led to the discovery of ravidasvir (PPI-668), which has been well tolerated and shown high sustained viral response rates as a key component in all-oral combination regimens in multiple human clinical trials.

Identification and Characterization of a Putative Manganese Export Protein in Vibrio cholerae.

Unlabelled: Manganese plays an important role in the cellular physiology and metabolism of bacterial species, including the human pathogen Vibrio cholerae The intracellular level of manganese ions is controlled through coordinated regulation of the import and export of this element. We have identified a putative manganese exporter (VC0022), named mneA (manganese exporter A), which is highly conserved among Vibrio spp. An mneA mutant exhibited sensitivity to manganese but not to other cations.

Identification of Novel O-Linked Glycosylated Toxoplasma Proteins by Vicia villosa Lectin Chromatography.

Toxoplasma gondii maintains its intracellular life cycle using an extraordinary arsenal of parasite-specific organelles including the inner membrane complex (IMC), rhoptries, micronemes, and dense granules. While these unique compartments play critical roles in pathogenesis, many of their protein constituents have yet to be identified. We exploited the Vicia villosa lectin (VVL) to identify new glycosylated proteins that are present in these organelles.

Nonredundant Roles of Iron Acquisition Systems in Vibrio cholerae.

Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, thrives in both marine environments and the human host. To do so, it must encode the tools necessary to acquire essential nutrients, including iron, under these vastly different conditions. A number of V.

Potent bisimidazole-based HCV NS5A inhibitors bearing annulated tricyclic motifs.

This Letter describes the synthesis and biological evaluation of a number of functionalized bisimidazoles bearing annulated tricyclic motifs as potent inhibitors of HCV NS5A protein. Compound 4 h, which contains a substituted tricyclic 6-6-6 xanthene, demonstrated broad genotypic spectrum, compelling potency, and good oral bioavailability with dose-dependent drug exposure level in multiple animal species.

Discovery of functionalized bisimidazoles bearing cyclic aliphatic-phenyl motifs as HCV NS5A inhibitors.

This Letter describes the discovery of a number of functionalized bisimidazoles bearing a cyclohexylphenyl, piperidylphenyl, or bicyclo[2,2,2]octylphenyl motif as HCV NS5A inhibitors. Compounds 2c, 4b and 6 have demonstrated low single-digit nM potency in gt-1a replicon and double-digit pM potency in gt-1b replicon, respectively. Moreover, both 4b and 6 have, respectively, exhibited good oral bioavailability in rats with a favorable liver/plasma ratio of the drug concentration.

Effects of allergic phenotype on respiratory symptoms and exacerbations in patients with chronic obstructive pulmonary disease.

Rationale: Chronic obstructive pulmonary disease (COPD) guidelines make no recommendations for allergy diagnosis or treatment.

Objectives: To determine whether an allergic phenotype contributes to respiratory symptoms and exacerbations in patients with COPD.

Methods: Two separate cohorts were analyzed: National Health and Nutrition Survey III (NHANES III) and the COPD and domestic endotoxin (CODE) cohort.

Improved electrical conductivity of graphene films integrated with metal nanowires.

Polycrystalline graphene grown by chemical vapor deposition (CVD) on metals and transferred onto arbitrary substrates has line defects and disruptions such as wrinkles, ripples, and folding that adversely affect graphene transport properties through the scattering of the charge carriers. It is found that graphene assembled with metal nanowires (NWs) dramatically decreases the resistance of graphene films. Graphene/NW films with a sheet resistance comparable to that of the intrinsic resistance of graphene have been obtained and tested as a transparent electrode replacing indium tin oxide films in electrochromic (EC) devices.

Molecular dissection of novel trafficking and processing of the Toxoplasma gondii rhoptry metalloprotease toxolysin-1.

Toxoplasma gondii utilizes specialized secretory organelles called rhoptries to invade and hijack its host cell. Many rhoptry proteins are proteolytically processed at a highly conserved SΦXE site to remove organellar targeting sequences that may also affect protein activity. We have studied the trafficking and biogenesis of a secreted rhoptry metalloprotease with homology to insulysin that we named toxolysin-1 (TLN1).

Identification of novel proteins in Neospora caninum using an organelle purification and monoclonal antibody approach.

Neospora caninum is an important veterinary pathogen that causes abortion in cattle and neuromuscular disease in dogs. Neospora has also generated substantial interest because it is an extremely close relative of the human pathogen Toxoplasma gondii, yet does not appear to infect humans. While for Toxoplasma there are a wide array of molecular tools and reagents available for experimental investigation, relatively few reagents exist for Neospora.

The moving junction protein RON8 facilitates firm attachment and host cell invasion in Toxoplasma gondii.

The apicomplexan moving junction (MJ) is a highly conserved structure formed during host cell entry that anchors the invading parasite to the host cell and serves as a molecular sieve of host membrane proteins that protects the parasitophorous vacuole from host lysosomal destruction. While recent work in Toxoplasma and Plasmodium has reinforced the composition of the MJ as an important association of rhoptry neck proteins (RONs) with micronemal AMA1, little is known of the precise role of RONs in the junction or how they are targeted to the neck subcompartment. We report the first functional analysis of a MJ/RON protein by disrupting RON8 in T.