TRPM2 is elevated in the tMCAO stroke model, transcriptionally regulated, and functionally expressed in C13 microglia.

We report the detailed expression profile of TRPM2 mRNA within the human central nervous system (CNS) and demonstrate increased TRPM2 mRNA expression at 1 and 4 weeks following ischemic injury in the rat transient middle cerebral artery occlusion (tMCAO) stroke model. Microglial cells play a key role in pathology produced following ischemic injury in the CNS and possess TRPM2, which may contribute to stroke-related pathological responses. We show that TRPM2 mRNA is present in the human C13 microglial cell line and is reduced by antisense treatment.

TRPV1 antagonist, SB-366791, inhibits glutamatergic synaptic transmission in rat spinal dorsal horn following peripheral inflammation.

The anti-hyperalgesic effects of TRPV1 receptor antagonists are well documented in animal models of pain, however, the precise site of their action is not known. Here we have examined the effects of the selective TRPV1 antagonist SB-366791 on glutamatergic synaptic transmission in substantia gelatinosa using spinal cord slices from either control rats or animals that had undergone a peripheral inflammation induced by intraplantar injection of Freund's complete adjuvant (FCA). In control animals, SB-366791 (30 microM) had no effect on spontaneous excitatory post-synaptic currents (sEPSC) or evoked EPSCs.

Properties of voltage-gated Na+ channels in the human rhabdomyosarcoma cell-line SJ-RH30: conventional and automated patch clamp analysis.

Conventional and automated patch clamp electrophysiology were used to characterise the Na+ current of the SJ-RH30 human rhabdomyosarcoma. In conventional recordings SJ-RH30 cells exhibited a fast activating, fast inactivating Na+ current at potentials positive to -40 mV; in full current-voltage curves maximum current occurred between -20 and -10 mV. Inactivation kinetics at 0 mV were biexponential with time constants of 0.

Discovery of SB-705498: a potent, selective and orally bioavailable TRPV1 antagonist suitable for clinical development.

Small molecule antagonists of the vanilloid receptor TRPV1 (also known as VR1) are disclosed. Pyrrolidinyl ureas such as 8 and 15 (SB-705498) emerged as lead compounds following optimisation of the previously described urea SB-452533. Pharmacological studies using electrophysiological and FLIPR-Ca2+-based assays showed that compounds such as 8 and 15 were potent antagonists versus the multiple chemical and physical modes of TRPV1 activation (namely capsaicin, acid and noxious heat).

Adsorption-induced scission of carbon-carbon bonds.

Covalent carbon-carbon bonds are hard to break. Their strength is evident in the hardness of diamonds and tensile strength of polymeric fibres; on the single-molecule level, it manifests itself in the need for forces of several nanonewtons to extend and mechanically rupture one bond. Such forces have been generated using extensional flow, ultrasonic irradiation, receding meniscus and by directly stretching a single molecule with nanoprobes.

KCNQ/Kv7 channel regulation of hippocampal gamma-frequency firing in the absence of synaptic transmission.

Synchronous neuronal firing can be induced in hippocampal slices in the absence of synaptic transmission by lowering extracellular Ca2+ and raising extracellular K+. However, the ionic mechanisms underlying this nonsynaptic synchronous firing are not well understood. In this study we have investigated the role of KCNQ/Kv7 channels in regulating this form of nonsynaptic bursting activity.

Inhibition of Ih reduces epileptiform activity in rodent hippocampal slices.

Hyperpolarization-activated cyclic nucleotide gated (HCN) ion channels regulate membrane potential, neurotransmitter release, and patterning of synchronized neuronal activity. Currently, there is an intense debate as to whether or not these ion channels play a pro- or anticonvulsant role in vivo. To gain an insight into this question, we have examined how inhibitors of the response mediated by HCN channels (referred to as I(h)) affect epileptiform activity induced in adult hippocampal slices.

Prediction of protein stability changes for single-site mutations using support vector machines.

Accurate prediction of protein stability changes resulting from single amino acid mutations is important for understanding protein structures and designing new proteins. We use support vector machines to predict protein stability changes for single amino acid mutations leveraging both sequence and structural information. We evaluate our approach using cross-validation methods on a large dataset of single amino acid mutations.

Transgenic mice over-expressing human beta-amyloid have functional nicotinic alpha 7 receptors.

A potentially major factor in the development of Alzheimer's disease is the enhanced production of soluble beta-amyloid peptide fragments amyloid beta peptide(1-40) and amyloid beta peptide(1-42). These amyloid peptides are generated by cleavage of the amyloid-precursor protein and aggregate spontaneously to form amyloid plaques, which are a classical pathological hallmark in Alzheimer's disease. Although the precise mechanisms are unknown, it is widely believed that amyloid peptides initiate the degenerative process, resulting in subsequent cognitive decline.

Effects of reduced return activated sludge flows and volume on anaerobic zone performance for a septic wastewater biological phosphorus removal system.

Enhanced biological phosphorous removal (EBPR) performance was found to be adequate with reduced return-activated sludge (RAS) flows (50% of available RAS) to the anaerobic tank and smaller-than-typical anaerobic zone volume (1.08 hours hydraulic retention time [HRT]). Three identical parallel biological nutrient removal pilot plants were fed with strong, highly fermented (160 mg/L volatile fatty acids [VFAs]), domestic and industrial wastewater from a full-scale wastewater treatment facility.

Characterisation of recombinant rat TRPM2 and a TRPM2-like conductance in cultured rat striatal neurones.

TRPM2, a member of the TRP ion channel family, is expressed both in the brain and immune cells of the monocyte lineage. Functionally, it is unique in its activation by intracellular ADP-ribose and both oxidative and nitrosative stress. To date studies of this channel have concentrated on human recombinant channels and rodent native preparations.

A pharmacological investigation of the role of GLUK5-containing receptors in kainate-driven hippocampal gamma band oscillations.

Low concentrations of kainate can induce gamma frequency (25-80 Hz) oscillations in hippocampal slices as well as other brain structures in vitro. Little is known, however, about the kainate receptor (KAR) subtypes that underlie this type of rhythmic neuronal network activity. In this study, the role of GLU(K5) subunit-containing KARs in kainate-induced hippocampal gamma frequency oscillations was assessed using GLU(K5)-selective pharmacological ligands.

Impact of RO-desalted water on distribution water qualities.

A large-scale pilot distribution study was conducted to investigate the impacts of blending different source waters on distribution water qualities, with an emphasis on metal release (i.e. corrosion).

SCRATCH: a protein structure and structural feature prediction server.

SCRATCH is a server for predicting protein tertiary structure and structural features. The SCRATCH software suite includes predictors for secondary structure, relative solvent accessibility, disordered regions, domains, disulfide bridges, single mutation stability, residue contacts versus average, individual residue contacts and tertiary structure. The user simply provides an amino acid sequence and selects the desired predictions, then submits to the server.

Mechanisms contributing to the exacerbated epileptiform activity in hippocampal slices expressing a C-terminal truncated GABA(B2) receptor subunit.

GABAergic synaptic transmission plays an important role in the patterning of epileptiform activity. We have previously shown that global loss of GABA(B) receptor function due to transgenic deletion of the GABA(B1) receptor subunit exacerbates epileptiform activity induced by pharmacological manipulations in hippocampal slices. Here we show that a similar hyperexcitable phenotype is observed in hippocampal slices prepared from a transgenic mouse expressing a GABA(B2) receptor subunit lacking its C terminal tail (the DeltaGB2-Ct mouse); a molecular manipulation that also produces complete loss of GABA(B) receptor function.

Conservation of functional and pharmacological properties in the distantly related temperature sensors TRVP1 and TRPM8.

Members of the transient receptor potential (TRP) superfamily of ion channels have now been defined as molecular transducers capable of reproducing the spectrum of temperature sensation exhibited by mammals. Because of their pivotal role in sensory transduction, many of these channels represent good targets for drug discovery. With a view to gaining further insight into the functional and pharmacological properties of these channels, we have used the whole-cell patch-clamp technique to study the human cold-sensitive menthol receptor transient receptor potential melastatin 8 (TRPM8) and compared its behavior with that of its distant relative, the heat-sensitive capsaicin-gated transient receptor potential vanilloid 1 (TRPV1).

Sexually transmitted infections among pregnant women attending antenatal clinics in Mongolia: potential impact on the Mongolian HIV epidemic.

We conducted Mongolia's first nation-wide cross-sectional survey of sexually transmitted infections (STIs) among pregnant women attending prenatal care. Among our 2000 participants, 386 (19.3%) were infected with Chlamydia trachomatis, 133 (6.

Quantitation of house dust mite allergens (Der f 1 and group 2) on the skin and hair of dogs.

Objective: To determine the concentration of house dust mite (HDM) allergens, Der f 1 and group 2, on the skin and hair of dogs and whether associations exist between the presence of Der f 1 and group 2 allergens on the skin and hair of dogs and household and dog characteristics.

Animals: 63 pet dogs from 50 homes.

Procedure: Dogs were weighed and body surface area in square meters was determined.