T cells reactive to an inducible heat shock protein induce disease in toxin-induced interstitial nephritis.

T cells reactive against immunodominant regions of inducible heat shock proteins (HSPs) have been identified in the chronic inflammatory lesions of several experimental autoimmune diseases. Since HSPs are known to be induced by a number of renal tubular epithelial cell toxins associated with chronic interstitial nephritis, we investigated the relevance of HSP expression and T cell reactivity to HSP70 in a model of progressive inflammatory interstitial nephritis. Chronic administration of cadmium chloride (CdCl2) to SJL/J mice induces HSP70 expression in renal tubular cells 4-5 wk before the development of interstitial mononuclear cell infiltrates. CdCl2 also induces HSP70 expression in cultured tubular epithelial cells from SJL/J mice. CD4+, TCR-alpha/beta+ T cell lines specific for an immunodominant HSP peptide are cytotoxic to heat stressed or CdCl2-treated renal tubular cells. Such HSP-reactive T cells mediate an inflammatory interstitial nephritis after adoptive transfer to CdCl2-treated mice at a time when immunoreactive HSP70 is detectable in the kidneys, but before the development of interstitial mononuclear cell infiltrates. T cells isolated from the nephritic kidneys of mice treated with CdCl2 for 13 wk are also cytotoxic to heat shocked or cadmium-treated tubular cells. These kidney-derived T cells additionally induced interstitial nephritis after passive transfer, indicating their pathogenic significance. Our studies strongly support a role for HSP-reactive T cells in CdCl2-induced interstitial nephritis and suggest that the induction of HSPs in the kidney by a multitude of "non-immune" events may initiate or facilitate inflammatory damage by HSP-reactive lymphocytes

New type of microengine using internal combustion of hydrogen and oxygen

Microsystems become part of everyday life but their application is restricted by lack of strong and fast motors (actuators) converting energy into motion. For example, widespread internal combustion engines cannot be scaled down because combustion reactions are quenched in a small space. Here we present an actuator with the dimensions 100x100x5 um^3 that is using internal combustion of hydrogen and oxygen as part of its working cycle. Water electrolysis driven by short voltage pulses creates an extra pressure of 0.5-4 bar for a time of 100-400 us in a chamber closed by a flexible membrane. When the pulses are switched off this pressure is released even faster allowing production of mechanical work in short cycles. We provide arguments that this unexpectedly fast pressure decrease is due to spontaneous combustion of the gases in the chamber. This actuator is the first step to truly microscopic combustion engines.Comment: Paper and Supplementary Information (to appear in Scientific Reports

A Systematic Review of Online Sex Addiction and Clinical Treatments Using CONSORT Evaluation

Researchers have suggested that the advances of the Internet over the past two decades have gradually eliminated traditional offline methods of obtaining sexual material. Additionally, research on cybersex and/or online sex addictions has increased alongside the development of online technology. The present study extended the findings from Griffiths’ (2012) systematic empirical review of online sex addiction by additionally investigating empirical studies that implemented and/or documented clinical treatments for online sex addiction in adults. A total of nine studies were identified and then each underwent a CONSORT evaluation. The main findings of the present review provide some evidence to suggest that some treatments (both psychological and/or pharmacological) provide positive outcomes among those experiencing difficulties with online sex addiction. Similar to Griffiths’ original review, this study recommends that further research is warranted to establish the efficacy of empirically driven treatments for online sex addiction

Hypophosphatasia

Hypophosphatasia is a rare inherited disorder characterized by defective bone and teeth mineralization, and deficiency of serum and bone alkaline phosphatase activity. The prevalence of severe forms of the disease has been estimated at 1/100 000

Aligning research to meet policy objectives for migrant families: an example from Canada

<p>Abstract</p> <p>Background</p> <p>'Evidence-based policy making' for immigrants is a complicated undertaking. In striving toward this goal, federal Canadian partners created the <it>Metropolis Project </it>in 1995 to optimize a two-way transfer of knowledge (researchers – policy makers) within five Canadian Centres of Excellence focused on migrants newly arrived in Canada. Most recently, <it>Metropolis </it>federal partners, including the Public Health Agency of Canada, defined one of six research priority areas as, immigrant 'families, children, and youth'. In order to build on previous work in the partnership, we sought to determine what has been studied within this research-policy partnership about immigrant 'families, children, and youth' since its inception.</p> <p>Methods</p> <p>Annual reports and working papers produced in the five Centres of Excellence between 1996–2006 were culled. Data on academic works were extracted, results coded according to eleven stated federal policy priority themes, and analyzed descriptively.</p> <p>Results</p> <p>139 academic works were reviewed. All federal priority themes, but few specific policy questions were addressed. The greatest volume of policy relevant works were identified for <it>Services </it>(n = 42) and <it>Education and Cultural Identity </it>(n = 39) priority themes.</p> <p>Conclusion</p> <p>Research conducted within the last 10 years is available to inform certain, not all, federal policy questions. Greater specificity in federal priorities can be expected to more clearly direct future research within this policy-research partnership.</p

An introduction to Graph Data Management

A graph database is a database where the data structures for the schema and/or instances are modeled as a (labeled)(directed) graph or generalizations of it, and where querying is expressed by graph-oriented operations and type constructors. In this article we present the basic notions of graph databases, give an historical overview of its main development, and study the main current systems that implement them

Chronic multifocal non-bacterial osteomyelitis in hypophosphatasia mimicking malignancy

BACKGROUND: Hypophosphatasia (HP) is characterized by a genetic defect in the tissue-nonspecific alkaline phosphatase (TNSALP) gene and predominantly an autosomal recessive trait. HP patients suffer from reduced bone mineralization. Biochemically, elevated concentrations of substrates of TNSALP, including pyridoxal-5'-phosphate and inorganic pyrophosphate occur in serum, tissues and urine. The latter has been associated with chronic inflammation and hyperprostaglandinism. CASE PRESENTATION: We report on 2 affected children presenting with multifocal inflammatory bone lesions mimicking malignancy: A 6 years old girl with short stature had been treated with human growth hormone since 6 months. Then she started to complain about a painful swelling of her left cheek. MRI suggested a malignant bone lesion. Bone biopsy, however, revealed chronic inflammation. A bone scan showed a second rib lesion. Since biopsy was sterile, the descriptive diagnosis of chronic non-bacterial osteomyelitis (CNO) was established. The diagnostic tests related to growth failure were repeated and subsequent analyses demonstrated a molecular defect in the TNSALP gene. The second girl (10 years old) complained about back pain after she had fallen from her bike. X rays of her spine revealed compressions of 2 thoracic vertebrae. At first these were considered trauma related, however a bone scan did show an additional lesion in the right 4(th )rib. A biopsy of this rib revealed a sterile lympho- plasmocytoid osteomyelitis suggesting multifocal CNO. Further analyses did show a decreased TNSALP in leukocytes and elevated pyridoxal phosphate in plasma, suggesting a heterozygous carrier status of HP. CONCLUSION: Chronic bone oedema in adult HP and chronic hyper-prostaglandinism in childhood HP do suggest that in some HP patients bone inflammation is present in conjunction with the metabolic defect. Sterile multifocal osteomyelitis could be demonstrated. Non-steroidal anti-inflammatory treatment achieved complete remission. These cases illustrate chronic inflammation of the bone as a new feature of HP

A major genetic locus in <i>Trypanosoma brucei</i> is a determinant of host pathology

The progression and variation of pathology during infections can be due to components from both host or pathogen, and/or the interaction between them. The influence of host genetic variation on disease pathology during infections with trypanosomes has been well studied in recent years, but the role of parasite genetic variation has not been extensively studied. We have shown that there is parasite strain-specific variation in the level of splenomegaly and hepatomegaly in infected mice and used a forward genetic approach to identify the parasite loci that determine this variation. This approach allowed us to dissect and identify the parasite loci that determine the complex phenotypes induced by infection. Using the available trypanosome genetic map, a major quantitative trait locus (QTL) was identified on T. brucei chromosome 3 (LOD = 7.2) that accounted for approximately two thirds of the variance observed in each of two correlated phenotypes, splenomegaly and hepatomegaly, in the infected mice (named &lt;i&gt;TbOrg1&lt;/i&gt;). In addition, a second locus was identified that contributed to splenomegaly, hepatomegaly and reticulocytosis (&lt;i&gt;TbOrg2&lt;/i&gt;). This is the first use of quantitative trait locus mapping in a diploid protozoan and shows that there are trypanosome genes that directly contribute to the progression of pathology during infections and, therefore, that parasite genetic variation can be a critical factor in disease outcome. The identification of parasite loci is a first step towards identifying the genes that are responsible for these important traits and shows the power of genetic analysis as a tool for dissecting complex quantitative phenotypic traits