Vgl1, a multi-KH domain protein, is a novel component of the fission yeast stress granules required for cell survival under thermal stress.

Multiple KH-domain proteins, collectively known as vigilins, are evolutionarily highly conserved proteins that are present in eukaryotic organisms from yeast to metazoa. Proposed roles for vigilins include chromosome segregation, messenger RNA (mRNA) metabolism, translation and tRNA transport. As a step toward understanding its biological function, we have identified the fission yeast vigilin, designated Vgl1, and have investigated its role in cellular response to environmental stress.

Functional dissection of the granzyme family: cell death and inflammation.

Cytotoxic lymphocytes rapidly respond and destroy both malignant cells and cells infected with intracellular pathogens. One mechanism, known as granule exocytosis, employs the secretory granules of these lymphocytes. These include the pore-forming protein perforin (pfp) and a family of serine proteases known as granzymes that cleave and activate effector molecules within the target cell.

Asymmetric cell division of T cells upon antigen presentation uses multiple conserved mechanisms.

Asymmetric cell division is a potential means by which cell fate choices during an immune response are orchestrated. Defining the molecular mechanisms that underlie asymmetric division of T cells is paramount for determining the role of this process in the generation of effector and memory T cell subsets. In other cell types, asymmetric cell division is regulated by conserved polarity protein complexes that control the localization of cell fate determinants and spindle orientation during division.

Development and implementation of training for interdisciplinary research in primary health care.

The authors describe a national training program in Canada focusing on research in primary health care (PHC). The program, sponsored by the Canadian Institutes of Health Research's Strategic Training in Health Research Program, is called Transdisciplinary Understanding and Training on Research-Primary Health Care (TUTOR-PHC); it began in 2002 and is funded to continue until 2015. The purpose-built curriculum has two main goals: (1) to build a cadre of skilled, independent researchers to enhance the evidence base for PHC practice and policy and (2) to increase the interdisciplinary focus in PHC research.

The cognitive profile of preschool-aged children with neurofibromatosis type 1.

Few studies have examined the cognitive profile of young children with NF1. In this study, 26 children with NF1 (M(age) = 5 years 3 months) were compared with 21 peer comparisons (M(age) = 4 years 8 months) and available normative data on neuropsychological measures. Children with NF1 demonstrated the characteristic downward shift in IQ, poor visuospatial constructional skills, and inattention.

Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding.

Transcription factors (TFs) direct gene expression by binding to DNA regulatory regions. To explore the evolution of gene regulation, we used chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq) to determine experimentally the genome-wide occupancy of two TFs, CCAAT/enhancer-binding protein alpha and hepatocyte nuclear factor 4 alpha, in the livers of five vertebrates. Although each TF displays highly conserved DNA binding preferences, most binding is species-specific, and aligned binding events present in all five species are rare.

Functional and morphological maturation of implanted neonatal cardiomyocytes as a comparator for cell therapy.

Knowledge of the rate of development of immature cardiomyocytes after implantation into a host heart is important for studies using cell therapy. To assess this functionally, we have implanted rat neonatal cardiomyocytes (NCMs) in normal and infarcted rat heart and re-isolated them for functional assessment. Maturation of implanted bone marrow stromal cells (BMSCs) was compared under similar conditions.

An acetylated form of histone H2A.Z regulates chromosome architecture in Schizosaccharomyces pombe.

Histone variant H2A.Z has a conserved role in genome stability, although it remains unclear how this is mediated. Here we demonstrate that the fission yeast Swr1 ATPase inserts H2A.

Hearing symptoms and audiometry in professional divers and offshore workers.

Aims: The aims are to compare hearing loss between professional divers and offshore workers and to study whether hearing loss symptoms reflected physical disorder. A secondary objective was to study total threshold shift assessment as a method of detecting noise-induced hearing loss (NIHL).

Methods: Participants (151 divers and 120 offshore workers) completed a questionnaire for symptoms and screening audiometry.

Integration of vision and haptics during tool use.

When integrating signals from vision and haptics the brain must solve a "correspondence problem" so that it only combines information referring to the same object. An invariant spatial rule could be used when grasping with the hand: here the two signals should only be integrated when the estimate of hand and object position coincide. Tools complicate this relationship, however, because visual information about the object, and the location of the hand, are separated spatially.

Clinical stem cell therapies for severe autoimmune diseases.

Severe autoimmune diseases (ADs) are a major source of disability and reduced quality of life and may result in shortened life expectancy, particularly in treatment-resistant patients. For several decades, allogeneic and autologous haematopoietic stem cell transplantation (HSCT) has been the focus of scientific investigation as a potential means of delivering 'one-off' intensive treatment in severe ADs. Improvements in the clinical safety of HCST were followed by its increasing use in recent years as an experimental treatment for severe and resistant ADs.

Stem cell-related therapies for vascular diseases.

The therapeutic potential of 'adult' or at least non-embryonic stem cells and their progeny has developed gradually over the past half century as a consequence of the wealth of knowledge derived from stem cell research. Translational research coupled with clinical trials and derived from basic research has led the way to the clinic. This commenced with the use of haematopoietic stem cell transplantation (HSCT), to treat haematological malignancies, to be followed by the most recent clinical trials to treat a variety of coronary and peripheral artery diseases.

Route of delivery and baseline left ventricular ejection fraction, key factors of bone-marrow-derived cell therapy for ischaemic heart disease.

Aims: Previous evaluation of autologous bone-marrow stem-cell (BMSC) therapy following acute myocardial infarction (AMI) suggests that cell dose and timing of stem-cell administration post-MI are important factors in the efficacy of cellular therapy. This study aimed to assess whether route of delivery and baseline left ventricular ejection fraction (LVEF) of the participants may also affect the outcome of BMSC treatment in patients with AMI and ischaemic heart disease (IHD).

Methods And Results: Randomized controlled trials of BMSCs as treatment for AMI and IHD were identified by searching MEDLINE, EMBASE, the Cochrane Library, and the Current Controlled Trials Register through to November 2008.

Comparison of CID versus ETD based MS/MS fragmentation for the analysis of protein ubiquitination.

Ubiquitination has emerged as one of the major post-translational modifications that decide on protein fate, targeting, and regulation of protein function. Whereas the ubiquitination of proteins can be monitored with classic biochemical methods, the mapping of modified side chains proves to be challenging. More recently, mass spectrometry has been applied to identify ubiquitinated proteins and also their sites of modification.

Cyclin-dependent kinase inhibits reinitiation of a normal S-phase program during G2 in fission yeast.

To achieve faithful replication of the genome once in each cell cycle, reinitiation of S phase is prevented in G(2) and origins are restricted from refiring within S phase. We have investigated the block to rereplication during G(2) in fission yeast. The DNA synthesis that occurs when G(2)/M cyclin-dependent kinase (CDK) activity is depleted has been assumed to be repeated rounds of S phase without mitosis, but this has not been demonstrated to be the case.

Intraspecies signaling involving the diffusible signal factor BDSF (cis-2-dodecenoic acid) influences virulence in Burkholderia cenocepacia.

Burkholderia cenocepacia produces a diffusible fatty acid signal molecule, cis-2-dodecenoic acid (BDSF), that has been implicated in interspecies and interkingdom communication. Here, we show that BDSF also acts as an intraspecies signal in B. cenocepacia to control factors contributing to virulence of this major opportunistic pathogen.

The Ontario Mother and Infant Study (TOMIS) III: a multi-site cohort study of the impact of delivery method on health, service use, and costs of care in the first postpartum year.

Background: The caesarean section rate continues to rise globally. A caesarean section is inarguably the preferred method of delivery when there is good evidence that a vaginal delivery may unduly risk the health of a woman or her infant. Any decisions about delivery method in the absence of clear medical indication should be based on knowledge of outcomes associated with different childbirth methods.

Clinical grade OK432-activated dendritic cells: in vitro characterization and tracking during intralymphatic delivery.

Dendritic cells (DC) are under intense preclinical and early clinical evaluation for the immunotherapy of cancer. However, the optimal culture conditions and route of delivery for DC vaccination have not been established. Here we describe the first human application of DC matured with the bacterial agent OK432 (OK-DC), using a short-term serum-free culture protocol, which generates mature DC from CD14+ precursors after 5 days.

The role of binocular vision in grasping: a small stimulus-set distorts results.

The role of binocular vision in grasping has frequently been assessed by measuring the effects on grasp kinematics of covering one eye. These studies have typically used three or fewer objects presented at three or fewer distances, raising the possibility that participants learn the properties of the stimulus set. If so, even relatively poor visual information may be sufficient to identify which object/distance configuration is presented on a given trial, in effect providing an additional source of depth information.

Effects of social belonging on homesickness: an application of the belongingness hypothesis.

Belongingness theory proposes that humans possess an innate drive for a minimum number of lasting interpersonal relationships. On geographic relocation, people leave their existing social networks. This greatly threatens belongingness needs, and the authors propose this is one cause of homesickness.

Improved tools for efficient mapping of fission yeast genes: identification of microtubule nucleation modifier mod22-1 as an allele of chromatin- remodelling factor gene swr1.

Fission yeast genes identified in genetic screens are usually cloned by transformation of mutants with plasmid libraries. However, for some genes this can be difficult, and positional cloning approaches are required. The mutation swi5-39 reduces recombination frequency in homozygous crosses and has been used as a tool in mapping gene position (Schmidt, 1993).

Low molecular weight plant extract induces metabolic changes and the secretion of extracellular enzymes, but has a negative effect on the expression of the type-III secretion system in Xanthomonas campestris pv. campestris.

Xanthomonas campestris pathovar campestris (Xcc) is a plant pathogenic bacterium and as such has to adapt to a variety of environments. During the course of disease, Xcc colonizes the surface of its host, infects the xylem in the early stages, and develops a fully saprophytic life-style, aided by secreted degradative enzymes, in the late stages. To get some insight into this complex regulation, Xcc was cultivated in the presence of low molecular weight host plant extract (<10 kDa).