Identification of GIG1, a GlcNAc-induced gene in Candida albicans needed for normal sensitivity to the chitin synthase inhibitor nikkomycin Z.

The amino sugar N-acetylglucosamine (GlcNAc) is known to be an important structural component of cells from bacteria to humans, but its roles in cell signaling are less well understood. GlcNAc induces two pathways in the human fungal pathogen Candida albicans. One activates cyclic AMP (cAMP) signaling, which stimulates the formation of hyphal cells and the expression of virulence genes, and the other pathway induces genes needed to catabolize GlcNAc.

Experience with a large-frame, disposable external fixator.

External fixation is a temporizing measure that has a long history in the treatment of fractures. Thirty-eight newly designed large-frame external fixators were applied for acute lower-limb fractures and pelvis injuries in a level I trauma center. In 75% of cases, the frames were used for first-stage skeletal stabilization, followed by revision to plates or nails 1 to 2 weeks later.

The alpha2delta subunits of voltage-gated calcium channels form GPI-anchored proteins, a posttranslational modification essential for function.

Voltage-gated calcium channels are thought to exist in the plasma membrane as heteromeric proteins, in which the alpha1 subunit is associated with two auxiliary subunits, the intracellular beta subunit and the alpha(2)delta subunit; both of these subunits influence the trafficking and properties of Ca(V)1 and Ca(V)2 channels. The alpha(2)delta subunits have been described as type I transmembrane proteins, because they have an N-terminal signal peptide and a C-terminal hydrophobic and potentially transmembrane region. However, because they have very short C-terminal cytoplasmic domains, we hypothesized that the alpha(2)delta proteins might be associated with the plasma membrane through a glycosylphosphatidylinositol (GPI) anchor attached to delta rather than a transmembrane domain.

A randomized comparison of online and paper mood charts for people with bipolar disorder.

Background: Longitudinal mood instability is the essential feature of bipolar disorder, however most rating scales are cross sectional in nature, and focus on acute symptoms. By contrast, the NIMH Life Chart Methodology (LCM) characterizes in detail the severity, duration, and frequency of mood episodes. Adherence to daily rating, however, tends to be low.

Apoptosis in Candida biofilms exposed to amphotericin B.

Candida biofilms are resistant to a range of antifungal agents in current clinical use. The basis of this drug resistance is not clear, but in some cases it could be due to the presence of a small number of drug-tolerant or persister cells. In this study, specific staining methods were used to investigate the existence of persisters and apoptosis in Candida biofilms subjected to different concentrations of amphotericin B.

The Sur7 protein resides in punctate membrane subdomains and mediates spatial regulation of cell wall synthesis in Candida albicans.

The eukaryotic plasma membrane is organized into distinct domains that contribute to its function. One new type of plasma membrane domain was identified by studies on the Sur7 protein, which was discovered in the yeast S. cerevisiae to localize into stable punctate patches known as MCC or eisosomes.

BAR domain proteins Rvs161 and Rvs167 contribute to Candida albicans endocytosis, morphogenesis, and virulence.

The Candida albicans plasma membrane plays critical roles in growth and virulence and as a target for antifungal drugs. Three C. albicans genes that encode Bin-Amphiphysin-Rvs homology domain proteins were mutated to define their roles in plasma membrane function.

Central venous access devices: review of practice.

Unlabelled: Management of central venous access devices is a complex nursing activity with the potential for serious complications. There are variations in the care and maintenance of these devices, between and within, hospitals. Building on previous literature reviews and audits, a postal survey was undertaken to inform review of practice guidelines.

Assessment of hepatic extraction fraction and input relative blood flow using dynamic hepatocyte-specific contrast-enhanced MRI.

Purpose: To assess the feasibility to use dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) as an imaging-based liver function test, and to compare two methods for deconvolutional analysis (DA) in healthy human subjects.

Materials And Methods: T(1)-weighted DHCE-MRI with the hepatocyte-specific contrast medium Gd-EOB-DTPA was performed in 20 healthy volunteers. DA was performed using truncated singular value decomposition (TSVD) and Fourier analysis with an appended tail (FA+Tail).

The increased trafficking of the calcium channel subunit alpha2delta-1 to presynaptic terminals in neuropathic pain is inhibited by the alpha2delta ligand pregabalin.

Neuropathic pain results from damage to the peripheral sensory nervous system, which may have a number of causes. The calcium channel subunit alpha(2)delta-1 is upregulated in dorsal root ganglion (DRG) neurons in several animal models of neuropathic pain, and this is causally related to the onset of allodynia, in which a non-noxious stimulus becomes painful. The therapeutic drugs gabapentin and pregabalin (PGB), which are both alpha(2)delta ligands, have antiallodynic effects, but their mechanism of action has remained elusive.

Penetration of antifungal agents through Candida biofilms.

A filter disk assay is described, which measures the penetration of antifungal agents through Candida biofilms. The technique involves forming a colony biofilm on a polycarbonate membrane filter, and capping it with a second, smaller membrane filter followed by a wetted paper disk of the type used in zone-of-inhibition assays. The entire assembly is transferred to agar medium containing the antifungal agent of interest.

Ocular toxicity and distribution of subconjunctival and intravitreal rapamycin in horses.

In vitro photosensitivity of rapamycin (RAPA) and ocular toxicity and distribution of intravitreal and subconjunctival RAPA was evaluated in normal horses. RAPA (2.5 mg, 5 mg, and 10 mg) was placed in 10 mL of PBS and maintained in a water bath at 37 degrees C, kept in the dark or subjected to room light, and sampled for up to 3 months for RAPA levels.

beta-Catenin is essential for survival of leukemic stem cells insensitive to kinase inhibition in mice with BCR-ABL-induced chronic myeloid leukemia.

Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia (CML) induced by the BCR-ABL oncogene is believed to be developed from leukemic stem cells (LSCs), and we have previously shown in mice that LSCs for CML express the same cell surface markers that are also expressed on normal hematopoietic stem cells (HSCs). Although the inhibition of BCR-ABL kinase activity by imatinib is highly effective in treating human Ph(+) CML in chronic phase, it is difficult to achieve molecular remission of the disease, suggesting that LSCs remain in patients. In this study, we find that following imatinib treatment, LSCs not only remained but also accumulated increasingly in bone marrow of CML mice.

The Sur7 protein regulates plasma membrane organization and prevents intracellular cell wall growth in Candida albicans.

The Candida albicans plasma membrane plays important roles in cell growth and as a target for antifungal drugs. Analysis of Ca-Sur7 showed that this four transmembrane domain protein localized to stable punctate patches, similar to the plasma membrane subdomains known as eisosomes or MCC that were discovered in S. cerevisiae.

Programming InterStim for faecal incontinence.

Objective: Sacral nerve stimulation (SNS) for faecal incontinence (FI) is achieved by implanting a pulse generator attached to a tined lead with individually programmable electrodes. Our aim was to establish whether the 'ideal' programme for the treatment of FI has been used most commonly. We also wished to determine whether re-programming changed the symptom severity scores.

Influence of doping rate in Er3+:ZnO films on emission characteristics.

High-quality Er(3+):ZnO films were grown by the pulsed-laser deposition technique for 0.5 and 2 wt. % Er doping.

Probiotics and prebiotics in dietetics practice.

Probiotics and prebiotics share a unique role in human nutrition, largely centering on manipulation of populations or activities of the bacteria that colonize our bodies. Benefits of regular consumption of probiotics or prebiotics include enhanced immune function, improved colonic integrity, decreased incidence and duration of intestinal infections, down-regulated allergic response, and improved digestion and elimination. Research has shown that probiotics and prebiotics may be useful in achieving these and other positive effects, provided that proper strain, product selection, and dosing guidelines of commercial products are followed.

EBV PCR in the diagnosis and monitoring of posttransplant lymphoproliferative disorder: results of a two-arm prospective trial.

While EBV PCR is used in the management of PTLD, the optimal primer set, relative importance of intracellular versus free plasma EBV, and the baseline profile in an organ transplant population remains unclear. We performed a prospective 2-arm trial utilizing an EBV PCR panel measuring LMP-1, EBER-1 and EBNA-1 in both free plasma as well as intracellular whole blood. Control Arm A consisted of 31 lung transplant patients and Arm B consisted of 35 transplant patients being evaluated for possible PTLD.

Absence of amphotericin B-tolerant persister cells in biofilms of some Candida species.

Biofilms and planktonic cells of five Candida species were surveyed for the presence of persister (drug-tolerant) cell populations after exposure to amphotericin B. None of the planktonic cultures (exponential or stationary phase) contained persister cells. However, persisters were found in biofilms of one of two strains of Candida albicans tested and in biofilms of Candida krusei and Candida parapsilosis, but not in biofilms of Candida glabrata or Candida tropicalis.

Expression and characterization of the flocculin Flo11/Muc1, a Saccharomyces cerevisiae mannoprotein with homotypic properties of adhesion.

The Flo11/Muc1 flocculin has diverse phenotypic effects. Saccharomyces cerevisiae cells of strain background Sigma1278b require Flo11p to form pseudohyphae, invade agar, adhere to plastic, and develop biofilms, but they do not flocculate. We show that S.

Association between elevated whole blood Epstein-Barr virus (EBV)-encoded RNA EBV polymerase chain reaction and reduced incidence of acute lung allograft rejection.

Background: Accurate functional assessment of patient immunosuppression after solid-organ transplantation remains elusive. Despite therapeutic serum immunosuppressive drug levels many lung transplant recipients still develop allograft rejection. We investigated the hypothesis that detection of latent Epstein-Barr virus (EBV) in peripheral blood may be a functional marker for the net effects of administered immunosuppression.

Histone deacetylase inhibitors enhance lexatumumab-induced apoptosis via a p21Cip1-dependent decrease in survivin levels.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially induces apoptosis in malignant cells by binding to the death receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). Several agents that therapeutically exploit this phenomenon are being developed. We investigated the anticancer activity of two novel, highly specific agonistic monoclonal antibodies to TRAIL-R1 (mapatumumab, HGS-ETR1) and TRAIL-R2 (lexatumumab, HGS-ETR2) in colon cancer cell lines.

Functional biology of the alpha(2)delta subunits of voltage-gated calcium channels.

In this review, we examine what is known about the mechanism of action of the auxiliary alpha2delta subunits of voltage-gated Ca(2+) (Ca(v)) channels. First, to provide some background on the alpha2delta proteins, we discuss the genes encoding these channels, in addition to the topology and predicted structure of the alpha2delta subunits. We then describe the effects of alpha2delta subunits on the biophysical properties of Ca(v) channels and their physiological function.