The impact of dental phobia on patient consent.

Dental anxiety is prevalent across a broad spectrum of the population. Dental phobia is extreme dental fear, which interferes with normal functioning. For any dental treatment, it is an ethical, legal and professional duty of dentists to obtain valid informed consent from their patients.

Task sharing within a managed clinical network to improve child health in Malawi.

Background: Eighty per cent of Malawi's 8 million children live in rural areas, and there is an extensive tiered health system infrastructure from village health clinics to district hospitals which refers patients to one of the four central hospitals. The clinics and district hospitals are staffed by nurses, non-physician clinicians and recently qualified doctors. There are 16 paediatric specialists working in two of the four central hospitals which serve the urban population as well as accepting referrals from district hospitals.

Selective Gating of Neuronal Activity by Intrinsic Properties in Distinct Motor Rhythms.

Many neural circuits show fast reconfiguration following altered sensory or modulatory inputs to generate stereotyped outputs. In the motor circuit of Xenopus tadpoles, I study how certain voltage-dependent ionic currents affect firing thresholds and contribute to circuit reconfiguration to generate two distinct motor patterns, swimming and struggling. Firing thresholds of excitatory interneurons [i.

Distinct circular single-stranded DNA viruses exist in different soil types.

The potential dependence of virus populations on soil types was examined by electron microscopy, and the total abundance of virus particles in four soil types was similar to that previously observed in soil samples. The four soil types examined differed in the relative abundances of four morphological groups of viruses. Machair, a unique type of coastal soil in western Scotland and Ireland, differed from the others tested in having a higher proportion of tailed bacteriophages.

Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis.

Background: Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis.

Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group).

mtsslSuite: spin labelling, trilateration and distance-constrained rigid body docking in PyMOL.

Nanometer distance measurements based on electron paramagnetic resonance methods in combination with site-directed spin labelling are powerful tools for the structural analysis of macromolecules. The software package mtsslSuite provides scientists with a set of tools for the translation of experimental distance distributions into structural information. The package is based on the previously published mtsslWizard software for spin labelling.

Late-acting self-incompatibility--the pariah breeding system in flowering plants.

It is estimated that around half of all species of flowering plants show self-incompatibility (SI). However, the great majority of species alleged to have SI simply comply with 'the inability of a fully fertile hermaphrodite plant to produce zygotes when self-pollinated'--a definition that is neutral as to cause. Surprisingly few species have been investigated experimentally to determine whether their SI has the type of genetic control found in one of the three established mechanisms, that is, homomorphic gametophytic, homomorphic sporophytic or heteromorphic SI.

The essential roles of cytidine diphosphate-diacylglycerol synthase in bloodstream form Trypanosoma brucei.

Lipid metabolism in Trypanosoma brucei, the causative agent of African sleeping sickness, differs from its human host in several fundamental ways. This has lead to the validation of a plethora of novel drug targets, giving hope of novel chemical intervention against this neglected disease. Cytidine diphosphate diacylglycerol (CDP-DAG) is a central lipid intermediate for several pathways in both prokaryotes and eukaryotes, being produced by CDP-DAG synthase (CDS).

How clerkship students learn from real patients in practice settings.

Purpose: To explore how undergraduate medical students learn from real patients in practice settings, the factors that affect their learning, and how clerkship learning might be enhanced.

Method: In 2009, 22 medical students in the three clerkship years of an undergraduate medical program in the United Kingdom made 119 near-contemporaneous audio diary entries reflecting how they learned from real patients. Nineteen attended focus groups; 18 were individually interviewed.

Development and characterization of glutamyl-protected N-hydroxyguanidines as reno-active nitric oxide donor drugs with therapeutic potential in acute renal failure.

Acute renal failure (ARF) has high mortality and no effective treatment. Nitric oxide (NO) delivery represents a credible means of preventing the damaging effects of vasoconstriction, central to ARF, but design of drugs with the necessary renoselectivity is challenging. Here, we developed N-hydroxyguanidine NO donor drugs that were protected against spontaneous NO release by linkage to glutamyl adducts that could be cleaved by γ-glutamyl transpeptidase (γ-GT), found predominantly in renal tissue.

A class of 5-nitro-2-furancarboxylamides with potent trypanocidal activity against Trypanosoma brucei in vitro.

Recently, the World Health Organization approved the nifurtimox-eflornithine combination therapy for the treatment of human African trypanosomiasis, renewing interest in nitroheterocycle therapies for this and associated diseases. In this study, we have synthesized a series of novel 5-nitro-2-furancarboxylamides that show potent trypanocidal activity, ∼1000-fold more potent than nifurtimox against in vitro Trypanosoma brucei with very low cytotoxicity against human HeLa cells. More importantly, the most potent analogue showed very limited cross-resistance to nifurtimox-resistant cells and vice versa.

Crystallization, dehydration and experimental phasing of WbdD, a bifunctional kinase and methyltransferase from Escherichia coli O9a.

WbdD is a bifunctional kinase/methyltransferase that is responsible for regulation of lipopolysaccharide O antigen polysaccharide chain length in Escherichia coli serotype O9a. Solving the crystal structure of this protein proved to be a challenge because the available crystals belonging to space group I23 only diffracted to low resolution (>95% of the crystals diffracted to resolution lower than 4 Å and most only to 8 Å) and were non-isomorphous, with changes in unit-cell dimensions of greater than 10%. Data from a serendipitously found single native crystal that diffracted to 3.

MtsslWizard: In Silico Spin-Labeling and Generation of Distance Distributions in PyMOL.

MtsslWizard is a computer program, which operates as a plugin for the PyMOL molecular graphics system. MtsslWizard estimates distances between spin labels on proteins quickly with user-configurable options through a simple graphical interface. In default mode, the program searches for ensembles of possible MTSSL conformations that do not clash with a static model of the protein.

Bacterial mechanosensitive channels--MscS: evolution's solution to creating sensitivity in function.

The discovery of mechanosensing channels has changed our understanding of bacterial physiology. The mechanosensitive channel of small conductance (MscS) is perhaps the most intensively studied of these channels. MscS has at least two states: closed, which does not allow solutes to exit the cytoplasm, and open, which allows rapid efflux of solvent and solutes.

Screening the MayBridge Rule of 3 Fragment Library for Compounds That Interact with the Trypanosoma brucei myo-Inositol-3-Phosphate Synthase and/or Show Trypanocidal Activity.

Inositol-3-phosphate synthase (INO1) has previously been genetically validated as a drug target against Trypanosoma brucei, the causative agent of African sleeping sickness. Chemical intervention of this essential enzyme could lead to new therapeutic agents. Unfortunately, no potent inhibitors of INO1 from any organism have been reported, so a screen for potential novel inhibitors of T.

Structural basis for acyl acceptor specificity in the achromobactin biosynthetic enzyme AcsD.

Siderophores are known virulence factors, and their biosynthesis is a target for new antibacterial agents. A non-ribosomal peptide synthetase-independent siderophore biosynthetic pathway in Dickeya dadantii is responsible for production of the siderophore achromobactin. The D.

The crystal structure of the Y140F mutant of ADP-L-glycero-D-manno-heptose 6-epimerase bound to ADP-beta-D-mannose suggests a one base mechanism.

Bacteria synthesize a wide array of unusual carbohydrate molecules, which they use in a variety of ways. The carbohydrate L-glycero-D-manno-heptose is an important component of lipopolysaccharide and is synthesized in a complex series of enzymatic steps. One step involves the epimerization at the C6'' position converting ADP-D-glycero-D-manno-heptose into ADP-L-glycero-D-manno-heptose.

Adenylate-forming enzymes.

Thioesters, amides, and esters are common chemical building blocks in a wide array of natural products. The formation of these bonds can be catalyzed in a variety of ways. For chemists, the use of an activating group is a common strategy and adenylate enzymes are exemplars of this approach.

Crystallization and preliminary crystallographic analysis of the bacterial capsule assembly-regulating tyrosine phosphatases Wzb of Escherichia coli and Cps4B of Streptococcus pneumoniae.

Bacterial tyrosine kinases and their cognate phosphatases are key players in the regulation of capsule assembly and thus are important virulence determinants of these bacteria. Examples of the kinase/phosphatase pairing are found in Gram-negative bacteria such as Escherichia coli (Wzc and Wzb) and in Gram-positive bacteria such as Streptococcus pneumoniae (CpsCD and CpsB). Although Wzb and Cps4B are both predicted to dephosphorylate the C-terminal tyrosine cluster of their cognate tyrosine kinase, they appear on the basis of protein sequence to belong to quite different enzyme classes.

Crystal structures of Wzb of Escherichia coli and CpsB of Streptococcus pneumoniae, representatives of two families of tyrosine phosphatases that regulate capsule assembly.

Many Gram-positive and Gram-negative bacteria utilize polysaccharide surface layers called capsules to evade the immune system; consequently, the synthesis and export of the capsule are a potential therapeutic target. In Escherichia coli K-30, the integral membrane tyrosine autokinase Wzc and the cognate phosphatase Wzb have been shown to be key for both synthesis and assembly of capsular polysaccharides. In the Gram-positive bacterium Streptococcus pneumoniae, the CpsCD complex is analogous to Wzc and the phosphatase CpsB is the corresponding cognate phosphatase.

PELDOR spectroscopy distance fingerprinting of the octameric outer-membrane protein Wza from Escherichia coli.

Distance fingerprinting: Pulsed electron-electron double resonance spectroscopy (PELDOR) is applied to the octameric membrane protein complex Wza of E. coli. The data yielded a detailed distance fingerprint of its periplasmic region that compares favorably to the crystal structure.

AcsD catalyzes enantioselective citrate desymmetrization in siderophore biosynthesis.

Bacterial pathogens need to scavenge iron from their host for growth and proliferation during infection. They have evolved several strategies to do this, one being the biosynthesis and excretion of small, high-affinity iron chelators known as siderophores. The biosynthesis of siderophores is an important area of study, not only for potential therapeutic intervention but also to illuminate new enzyme chemistries.

Guanylin-like peptides, guanylate cyclase and osmoregulation in the European eel (Anguilla anguilla).

Three guanylin-like peptides, guanylin, uroguanylin and renoguanylin and two guanylate cyclase type C (GC-C) receptor isoforms were cloned and sequenced from the European eel (Anguilla anguilla). All peptides and both receptors (GC-C1 and GC-C2) were predominantly expressed within the intestine and kidney of both sexually immature yellow, and sexually maturing, migratory silver eels. The derived amino acid sequences for the pre-prohormones and guanylate cyclase isoforms had structural features in common with sequences previously reported for guanylin-like peptides and guanylate cyclases from teleost fish and other species in general.

Synthesis of microporous materials using macrocycles as structure directing agents.

The synthesis of microporous materials has been an important element of solid state chemistry over the past years and remains so today. The emergence of possible new applications has driven interest towards synthesis of new materials. This article reviews the application of macrocycles as structure-directing agents (SDAs) in the pursuit of these important new materials.

Structural and kinetic characterization of quinolinate phosphoribosyltransferase (hQPRTase) from homo sapiens.

Human quinolinate phosphoribosyltransferase (EC 2.4.2.