Role of helicase-like transcription factor (hltf) in the G2/m transition and apoptosis in brain.

HLTF participates in transcription, chromatin remodeling, DNA damage repair, and tumor suppression. Aside from being expressed in mouse brain during embryonic and postnatal development, little is known about Hltf's functional importance. Splice variant quantification of wild-type neonatal (6-8 hour postpartum) brain gave a ratio of 5:1 for Hltf isoform 1 (exons 1-25) to isoform 2 (exons 1-21 with exon 21 extended via a partial intron retention event).

Antitubercular specific activity of ibuprofen and the other 2-arylpropanoic acids using the HT-SPOTi whole-cell phenotypic assay.

Objectives: Lead antituberculosis (anti-TB) molecules with novel mechanisms of action are urgently required to fuel the anti-TB drug discovery pipeline. The aim of this study was to validate the use of the high-throughput spot culture growth inhibition (HT-SPOTi) assay for screening libraries of compounds against Mycobacterium tuberculosis and to study the inhibitory effect of ibuprofen (IBP) and the other 2-arylpropanoic acids on the growth inhibition of M tuberculosis and other mycobacterial species.

Methods: The HT-SPOTi method was validated not only with known drugs but also with a library of 47 confirmed anti-TB active compounds published in the ChEMBL database.

Microfab-less Microfluidic Capillary Electrophoresis Devices.

Compared to conventional bench-top instruments, microfluidic devices possess advantageous characteristics including great portability potential, reduced analysis time (minutes), and relatively inexpensive production, putting them on the forefront of modern analytical chemistry. Fabrication of these devices, however, often involves polymeric materials with less-than-ideal surface properties, specific instrumentation, and cumbersome fabrication procedures. In order to overcome such drawbacks, a new hybrid platform is proposed.

Characterisation of ATP-dependent Mur ligases involved in the biogenesis of cell wall peptidoglycan in Mycobacterium tuberculosis.

ATP-dependent Mur ligases (Mur synthetases) play essential roles in the biosynthesis of cell wall peptidoglycan (PG) as they catalyze the ligation of key amino acid residues to the stem peptide at the expense of ATP hydrolysis, thus representing potential targets for antibacterial drug discovery. In this study we characterized the division/cell wall (dcw) operon and identified a promoter driving the co-transcription of mur synthetases along with key cell division genes such as ftsQ and ftsW. Furthermore, we have extended our previous investigations of MurE to MurC, MurD and MurF synthetases from Mycobacterium tuberculosis.

Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages.

Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M.

Versatile routes to marine sponge metabolites through benzylidene rhodanines.

The first total synthesis of the marine natural products Psammaplin C and Tokaradine A is described. Benzylidene rhodanines were utilized as versatile intermediates toward the synthesis of seven brominated marine sponge metabolites through the optimization of protection group strategies. Spermatinamine demonstrated good inhibition of all cancer cell lines tested, in particular the leukemia K562 and colon cancer HT29 cell lines.

Feasibility, safety, and efficacy of the combination of D-serine and computerized cognitive retraining in schizophrenia: an international collaborative pilot study.

The combination of pharmacotherapy and cognitive retraining (CRT) for the cognitive deficits of schizophrenia may be more efficacious than either approach alone, but this has not yet been tested. This study evaluated the feasibility, safety, tolerability, and efficacy of 12 weeks of D-serine, combined with CRT in the treatment of cognitive deficits in schizophrenia at two academic sites in parallel, in India and the United States. In a randomized, partial double-blind, placebo-controlled, parallel-group design, 104 schizophrenia subjects (US site=22, Indian site=82) were randomized to: (1) D-serine (30 mg/kg)+CRT (5 h/week), (2) D-serine+control CRT, (3) CRT+placebo D-serine, and (4) placebo+control CRT.

The 3rd Schizophrenia International Research Society Conference, 14-18 April 2012, Florence, Italy: summaries of oral sessions.

The 3rd Schizophrenia International Research Society Conference was held in Florence, Italy, April 14-18, 2012 and this year had as its emphasis, "The Globalization of Research". Student travel awardees served as rapporteurs for each oral session and focused their summaries on the most significant findings that emerged and the discussions that followed. The following report is a composite of these summaries.

Antimycobacterials from lovage root (Ligusticum officinale Koch).

The n-hexane extract of Lovage root was found to significantly inhibit the growth of both Mycobacterium smegmatis mc²155 and Mycobacterium bovis BCG, and therefore a bioassay-guided isolation strategy was undertaken. (Z)-Ligustilide, (Z)-3-butylidenephthalide, (E)-3-butylidenephthalide, 3-butylphthalide, α-prethapsenol, falcarindiol, levistolide A, psoralen and bergapten were isolated by chromatographic techniques, characterized by NMR spectroscopy and MS, and evaluated for their growth inhibition activity against Mycobacterium tuberculosis H₃₇Rv using the whole-cell phenotypic spot culture growth inhibition assay (SPOTi). Cytotoxicity against RAW 264.

Implant-retained overdentures: a review.

Unlabelled: Implant-retained overdentures represent a treatment option for many patients unable to tolerate conventional dentures. They may be specifically indicated in patients with altered anatomy, neuromuscular disorders, a pronounced gag reflex or severe residual ridge resorption. This article discusses the different ways in which implant overdentures can be retained, outlines some of the clinical stages involved in planning and providing these prostheses, and highlights long-term maintenance requirements associated with implant-retained overdentures.

The COMT Met158 allele and violence in schizophrenia: a meta-analysis.

Background: The Met158 allele of catechol-O-methyl transferase (COMT) gene is associated with increased levels of catecholamines in the prefrontal cortex and may increase the likelihood of aggressiveness. We conducted a meta-analysis to test the hypothesis that the Met158 allele of the COMT gene is associated with aggressive and violent behavior in schizophrenia.

Methods: MEDLINE search (12/31/11) yielded 14 studies examining the association of the COMT gene polymorphism (rs4680) and aggression in schizophrenia (total n=2219).

Synthesis and antibacterial evaluation of a new series of N-Alkyl-2-alkynyl/(E)-alkenyl-4-(1H)-quinolones.

To gain further insight into the structural requirements of the aliphatic group at position 2 for their antimycobacterial activity, some N-alkyl-4-(1H)-quinolones bearing position 2 alkynyls with various chain length and triple bond positions were prepared and tested for in vitro antibacterial activity against rapidly-growing strains of mycobacteria, the vaccine strain Mycobacterium bovis BCG, and methicillin-resistant Staphylococcus aureus strains, EMRSA-15 and -16. The compounds were also evaluated for inhibition of ATP-dependent MurE ligase of Mycobacterium tuberculosis. The lowest MIC value of 0.

Determination of relative in vivo osteoconductivity of modified potassium fluorrichterite glass-ceramics compared with 45S5 bioglass.

Potassium fluorrichterite (KNaCaMg(5)Si(8)O(22)F(2)) glass-ceramics were modified by either increasing the concentration of calcium (GC5) or by the addition of P(2)O(5) (GP2). Rods (2 × 4 mm) of stoichiometric fluorrichterite (GST), modified compositions (GC5 and GP2) and 45S5 bioglass, which was used as the reference material, were prepared using a conventional lost-wax technique. Osteoconductivity was investigated by implantation into healing defects in the midshaft of rabbit femora.

Nicotine fails to attenuate ketamine-induced cognitive deficits and negative and positive symptoms in humans: implications for schizophrenia.

Background: The uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, ketamine, induces a range of symptoms resembling those seen in schizophrenia. Enhancement of nicotinic acetylcholine receptor (nAChR) function may have potential as a treatment for the cognitive deficits and negative symptoms of schizophrenia. Accordingly, we examined the modulatory effects of brain nAChR systems on NMDAR antagonist-induced effects.

Synthesis and biological evaluation of purpurealidin E-derived marine sponge metabolites: aplysamine-2, aplyzanzine A, and suberedamines A and B.

Five purpurealidin-derived marine secondary sponge metabolies have been synthesized through the carbodiimide coupling of an appropriate bromotyrosine unit. The structure elucidations have been confirmed through direct comparison with spectroscopic data of isolated natural products. Aplyzanzine A has been shown to be the most active product against a broad bacterial and fungal screen, demonstrating MIC values 2 to 4 times lower than the other metabolites in this study.

Antioxidant, antitubercular and cytotoxic activities of Piper imperiale.

Phenolic compounds are widely distributed in Nature and act as pharmacologically active constituents in many herbal medicines. They have multiple biological properties, most notably antioxidant, antibacterial and cytotoxic activities. In the present study an attempt to correlate the phenolic composition of leaf, flower and wood extracts of Piper imperiale, with antioxidant, antitubercular and cytotoxic activities was undertaken.

Prosthodontic complications associated with implant retained crowns and bridgework: a review of the literature.

This article reviews the incidence, aetiology, prevention and management of prosthodontic complications, which may occur following the delivery of implant retained crowns and bridgework. Problems associated with the calculation of complication rates are discussed. Examples of common complications and their management are presented.

An integrated surrogate model for screening of drugs against Mycobacterium tuberculosis.

Objectives: The intracellularly surviving and slow-growing pathogen, Mycobacterium tuberculosis, adapts the host cell environment for its active and dormant life cycle. It is evident that the lack of appropriate high-throughput screening of inhibitors within host cells is an impediment for the early stages of anti-tubercular drug discovery. We aimed to develop an integrated surrogate model that enhances the screening of large inhibitor libraries.

Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates.

The reactive thiol in cysteine is used for coupling maleimide linkers in the generation of antibody conjugates. To assess the impact of the conjugation site, we engineered cysteines into a therapeutic HER2/neu antibody at three sites differing in solvent accessibility and local charge. The highly solvent-accessible site rapidly lost conjugated thiol-reactive linkers in plasma owing to maleimide exchange with reactive thiols in albumin, free cysteine or glutathione.

Antimycobacterials from natural sources: ancient times, antibiotic era and novel scaffolds.

Mycobacteria are a group of aerobic, non-motile, acid fast bacteria that have a characteristic cell wall composed of a mycolyl-arabinogalactan-peptidoglycan complex. They display different phenotypic attributes in their growth, color and biochemistry. Tuberculosis (TB) is defined as the infection with Mycobacterium tuberculosis complex and was declared a global health emergency principally because of the appearance of multidrug-resistant strains and the associated risk of infection in immune-compromised population.

An antibacterial from Hypericum acmosepalum inhibits ATP-dependent MurE ligase from Mycobacterium tuberculosis.

In a project to characterise new antibacterial chemotypes from plants, hyperenone A and hypercalin B were isolated from the hexane and chloroform extracts of the aerial parts of Hypericum acmosepalum. The structures of both compounds were characterised by extensive one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and were confirmed by mass spectrometry. Hyperenone A and hypercalin B exhibited antibacterial activity against multidrug-resistant strains of Staphylococcus aureus, with minimum inhibition concentration ranges of 2-128 mg/L and 0.

Impressions in implant dentistry.

Unlabelled: Accurate impressions provide a foundation for successful implant prosthodontics. This paper is aimed at the general dental practitioner (GDP) who would like to start restoring dental implants and demystifies the terminology, introduces the basic armamentarium and discusses the relative merits of different implant impression techniques. Detailed, step-by-step instructions for making impressions using the closed and open tray techniques are provided and the importance of verification jigs are highlighted.

Characterization of an oxidoreductase from the arylamine N-acetyltransferase operon in Mycobacterium smegmatis.

Mycobacterium tuberculosis, the most successful bacterial pathogen, causes tuberculosis, a disease that still causes more than 2 million deaths per year. Arylamine N-acetyltransferase is an enzyme that is conserved in most Mycobacterium spp. The nat gene belongs to an operon that is important for the intracellular survival of M.

The safety of studies with intravenous Δ⁹-tetrahydrocannabinol in humans, with case histories.

Rationale: Delta-9-tetrahydrocannabinol (THC) is one of the few cannabinoid receptor ligands that can be used to probe the cannabinoid system in humans. Despite increasing interest in the cannabinoid receptor system, use of intravenous THC as a research tool has been limited by concerns about its abuse liability and psychoactive effects.

Objectives: This study aims to evaluate the safety of all intravenous THC studies conducted at this center for the past 13 years.

Mycobacterium tuberculosis: immune evasion, latency and reactivation.

One-third of the global human population harbours Mycobacterium tuberculosis in dormant form. This dormant or latent infection presents a major challenge for global efforts to eradicate tuberculosis, because it is a vast reservoir of potential reactivation and transmission. This article explains how the pathogen evades the host immune response to establish a latent infection, and how it emerges from a state of latency to cause reactivation disease.