A comparison of scan and focal sampling for the description of wild primate activity, diet and intragroup spatial relationships.

We used data collected during two concurrent studies of black howler monkeys (Alouatta pigra) in Palenque National Park, Mexico, to compare systematically three methods of behavioral data collection [group activity scan sampling (group scans), instantaneous focal individual sampling (instantaneous focals) and continuous focal individual sampling (continuous focals)] and three methods of proximity data collection [group proximity scan sampling (group proximity scans), focal individual proximity scan sampling (focal proximity scans) and instantaneous focal individual nearest neighbor sampling (focal nearest neighbor samples)]. We conducted pairwise comparisons of data among methods using Pearson correlations and one-sample t tests. A series of Kruskal-Wallis tests were performed to compare the activity and proximity patterns of adult males, adult females and juveniles described by each method.

The Know Your Numbers (KYN) program 2008 to 2010: impact on knowledge and health promotion behavior among participants.

Background: Since 2007, the National Stroke Foundation in Australia has undertaken a community-based 'Know Your Numbers' program on blood pressure and other stroke risk factors.

Aims: The aims of this study are to assess, in a sample of registrants participating in a three-month follow-up survey, retention of knowledge of risk factors and health conditions associated with hypertension, and whether those who were advised to see their doctor sought treatment or performed other health promotion actions.

Methods: Various organizations (mainly pharmacies) were recruited to offer a 'free' standardized blood pressure check and educational resources for one-week/year between 2008 and 2010.

Co-translational targeting and translocation of proteins to the endoplasmic reticulum.

Co-translational protein targeting to the endoplasmic reticulum (ER), represents an evolutionary-conserved mechanism to target proteins into the secretory pathway. In this targeting pathway proteins possessing signal sequences are recognised at the ribosome by the signal recognition particle while they are still undergoing synthesis. This triggers their delivery to the ER protein translocation channel, where they are directly translocated into the ER.

Secreted Threonyl-tRNA synthetase stimulates endothelial cell migration and angiogenesis.

Aminoacyl-tRNA synthetases classically regulate protein synthesis but some also engage in alternative signaling functions related to immune responses and angiogenesis. Threonyl-tRNA synthetase (TARS) is an autoantigen in the autoimmune disorder myositis, and borrelidin, a potent inhibitor of TARS, inhibits angiogenesis. We explored a mechanistic link between these findings by testing whether TARS directly affects angiogenesis through inflammatory mediators.

Development of a flow cytometry live cell assay for the screening of inhibitors of hepatitis C virus (HCV) replication.

In this study, we established a flow cytometry live cell-based assay that permits the screening of hepatitis C virus (HCV) inhibitors. Specifically, we created a stable cell line, which harbors a subgenomic replicon encoding an NS5A-YFP fusion protein. This system allows direct measurement of YFP fluorescence in live hepatoma cells in which the HCV replicon replicates.

Delivery of ricin toxin a-chain by peptide-targeted mesoporous silica nanoparticle-supported lipid bilayers.

Mesoporous silica nanoparticle-supported lipid bilayers, or "protocells", exhibit a high loading capacity, enhanced colloidal stability, and peptide-directed, cell-specific uptake, making them especially well-suited for targeted delivery of protein toxins to cancer. Protocells loaded with ricin toxin A-chain (RTA) and targeted to hepatocellular carcinoma cause complete cell death at 30 pM of RTA without affecting the viability of control hepatocytes.

Recombinant strains for the enhanced production of bioengineered rapalogs.

The rapK gene required for biosynthesis of the DHCHC starter acid that initiates rapamycin biosynthesis was deleted from strain BIOT-3410, a derivative of Streptomyces rapamycinicus which had been subjected to classical strain and process development and capable of robust rapamycin production at titres up to 250mg/L. The resulting strain BIOT-4010 could no longer produce rapamycin, but when supplied exogenously with DHCHC produced rapamycin at titres equivalent to its parent strain. This strain enabled mutasynthetic access to new rapalogs that could not readily be isolated from lower titre strains when fed DHCHC analogs.

Synthesis and immunological evaluation of self-assembling and self-adjuvanting tricomponent glycopeptide cancer-vaccine candidates.

Self-adjuvanting tricomponent vaccines were prepared and assessed for their self-assembly and immunological activity in mouse models. The vaccines each consisted of a peptide or glycopeptide antigen that corresponds to a complete copy of the variable-number tandem repeat (VNTR) of the tumor-associated mucin 1 (MUC1) glycoprotein, the universal T-cell helper peptide epitope PADRE, and the immunoadjuvant Pam(3)CysSer. The vaccines were shown to spontaneously self-assemble in water to form isotropic particles varying in size from 17 to 25 nm and elicited robust humoral responses in murine models without the addition of an external adjuvant.

Is pre-operative imaging essential prior to ureteric stone surgery?

Introduction: The aim of this study was to identify patients not requiring ureteric stone surgery based on pre-operative imaging (within 24 hours) prior to embarking on semirigid ureteroscopy (R-URS) for urolithiasis.

Methods: The imaging of all consecutive patients on whom R-URS for urolithiasis was performed over a 12-month period was reviewed. All patients had undergone a plain x-ray of the kidney, ureters and bladder (KUB), abdominal non-contrast computed tomography (NCCT-KUB) or both on the day of surgery.

Application of orange essential oil as an antistaphylococcal agent in a dressing model.

Background: Staphylococcus aureus is the pathogen most often and prevalently involved in skin and soft tissue infections. In recent decades outbreaks of methicillin-resistant S. aureus (MRSA) have created major problems for skin therapy, and burn and wound care units.

Tofacitinib or adalimumab versus placebo in rheumatoid arthritis.

Background: Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated for the treatment of rheumatoid arthritis.

Methods: In this 12-month, phase 3 trial, 717 patients who were receiving stable doses of methotrexate were randomly assigned to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, 40 mg of adalimumab once every 2 weeks, or placebo. At month 3, patients in the placebo group who did not have a 20% reduction from baseline in the number of swollen and tender joints were switched in a blinded fashion to either 5 mg or 10 mg of tofacitinib twice daily; at month 6, all patients still receiving placebo were switched to tofacitinib in a blinded fashion.

Fatty acids regulate stress resistance and virulence factor production for Listeria monocytogenes.

Fatty acids (FAs) are the major structural component of cellular membranes, which provide a physical and chemical barrier that insulates intracellular reactions from environmental fluctuations. The native composition of membrane FAs establishes the topological and chemical parameters for membrane-associated functions and is therefore modulated diligently by microorganisms especially in response to environmental stresses. However, the consequences of altered FA composition during host-pathogen interactions are poorly understood.

Multiple mutations in hepatitis C virus NS5A domain II are required to confer a significant level of resistance to alisporivir.

Alisporivir is the most advanced host-targeting antiviral cyclophilin (Cyp) inhibitor in phase III studies and has demonstrated a great deal of promise in decreasing hepatitis C virus (HCV) viremia in infected patients. In an attempt to further elucidate the mechanism of action of alisporivir, HCV replicons resistant to the drug were selected. Interestingly, mutations constantly arose in domain II of NS5A.

Tea tree oil-induced transcriptional alterations in Staphylococcus aureus.

Tea tree oil (TTO) is a steam distillate of Melaleuca alternifolia that demonstrates broad-spectrum antibacterial activity. This study was designed to document how TTO challenge influences the Staphylococcus aureus transcriptome. Overall, bioinformatic analyses (S.

Chromatin immunoprecipitation identifies genes under direct VraSR regulation in Staphylococcus aureus.

Transcriptional profiling of Staphylococcus aureus treated with cell wall-active antibiotics identified the 2-component system, VraSR, as one of the key players in response to antibiotic stress. Although it has been shown that a number of genes are regulated by the VraSR system, it has not been shown which genes are under direct VraSR regulation and which genes are not. In this study, chromatin immunoprecipitation techniques were used to identify the genes which are regulated by the direct interaction of VraR with their promoter regions.

Bioengineering natural product biosynthetic pathways for therapeutic applications.

With the advent of next-generation DNA sequencing technologies, the number of microbial genome sequences has increased dramatically, revealing a vast array of new biosynthetic gene clusters. Genomics data provide a tremendous opportunity to discover new natural products, and also to guide the bioengineering of new and existing natural product scaffolds for therapeutic applications. Notably, it is apparent that the vast majority of biosynthetic gene clusters are either silent or produce very low quantities of the corresponding natural products.

Synthesis of the bacteriocin glycopeptide sublancin 168 and S-glycosylated variants.

The synthesis of sublancin 168, a unique S-glucosylated bacteriocin antibiotic, is described. The natural product and two S-glycosylated variants were successfully prepared via native chemical ligation followed by folding. The synthetic glycopeptides were shown to possess primarily an α-helical secondary structure by CD and NMR studies.

Further insights into the mode of action of the lipoglycopeptide telavancin through global gene expression studies.

Telavancin is a novel semisynthetic lipoglycopeptide derivative of vancomycin with a decylaminoethyl side chain that is active against Gram-positive bacteria, including Staphylococcus aureus strains resistant to methicillin or vancomycin. A dual mechanism of action has been proposed for telavancin involving inhibition of peptidoglycan biosynthesis and membrane depolarization. Here we report the results of genome-wide transcriptional profiling of the response of S.

Antimicrobial effect and mode of action of terpeneless cold-pressed Valencia orange essential oil on methicillin-resistant Staphylococcus aureus.

Aims: The objectives of this study were to evaluate the antistaphylococcal effect and elucidate the mechanism of action of orange essential oil against antibiotic-resistant Staphylococcus aureus strains.

Methods And Results: The inhibitory effect of commercial orange essential oil (EO) against six Staph. aureus strains was tested using disc diffusion and agar dilution methods.

The early radiological results of the uncemented Oxford medial compartment knee replacement.

We carried out a prospective investigation into the radiological outcomes of uncemented Oxford medial compartment unicondylar replacement in 220 consecutive patients (231 knees) performed in a single centre with a minimum two-year follow-up. The functional outcomes using the mean Oxford knee score and the mean high-activity arthroplasty score were significantly improved over the pre-operative scores (p < 0.001).

Design and synthesis of thiourea compounds that inhibit transmembrane anchored carbonic anhydrases.

A library of 32 novel glycoconjugate thiourea-bridged benzene sulfonamides have been synthesized from the reaction of glycosyl isothiocyanates with a panel of simple benzene sulfonamides comprising either a free amine or hydrazide. All compounds were investigated for their ability to inhibit the enzymatic activity of five human carbonic anhydrase (hCA) isozymes: hCA I, II and membrane-associated isozymes IX, XII and XIV. A physicochemical feature of the free sugar thioureido glycoconjugates was high water solubility (> 20 mg/mL), as well many of these compounds exhibited a desirable potency and CA isozyme selectivity profile.

Delivery of small interfering RNA by peptide-targeted mesoporous silica nanoparticle-supported lipid bilayers.

The therapeutic potential of small interfering RNAs (siRNAs) is severely limited by the availability of delivery platforms that protect siRNA from degradation, deliver it to the target cell with high specificity and efficiency, and promote its endosomal escape and cytosolic dispersion. Here we report that mesoporous silica nanoparticle-supported lipid bilayers (or "protocells") exhibit multiple properties that overcome many of the limitations of existing delivery platforms. Protocells have a 10- to 100-fold greater capacity for siRNA than corresponding lipid nanoparticles and are markedly more stable when incubated under physiological conditions.

An antibiotic that inhibits a late step in wall teichoic acid biosynthesis induces the cell wall stress stimulon in Staphylococcus aureus.

Wall teichoic acids (WTAs) are phosphate-rich, sugar-based polymers attached to the cell walls of most Gram-positive bacteria. In Staphylococcus aureus, these anionic polymers regulate cell division, protect cells from osmotic stress, mediate host colonization, and mask enzymatically susceptible peptidoglycan bonds. Although WTAs are not required for survival in vitro, blocking the pathway at a late stage of synthesis is lethal.