Detection of a low-grade enteroviral infection in the islets of Langerhans of living patients newly diagnosed with type 1 diabetes

Journal ArticleThis is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version is available in Diabetes, May 2015, vol. 64, no. 5 pp. 1682-1687 in print and online at http://diabetes.diabetesjournals.org/content/64/5/1682.abstractThe Diabetes Virus Detection study (DiViD) is the first to examine fresh pancreatic tissue at the diagnosis of type 1 diabetes for the presence of viruses. Minimal pancreatic tail resection was performed 3-9 weeks after onset of type 1 diabetes in six adult patients (age 24-35 years). The presence of enteroviral capsid protein 1 (VP1) and the expression of class I HLA were investigated by immunohistochemistry. Enterovirus RNA was analyzed from isolated pancreatic islets and from fresh-frozen whole pancreatic tissue using PCR and sequencing. Nondiabetic organ donors served as controls. VP1 was detected in the islets of all type 1 diabetic patients (two of nine controls). Hyperexpression of class I HLA molecules was found in the islets of all patients (one of nine controls). Enterovirus-specific RNA sequences were detected in four of six patients (zero of six controls). The results were confirmed in various laboratories. Only 1.7% of the islets contained VP1(+) cells, and the amount of enterovirus RNA was low. The results provide evidence for the presence of enterovirus in pancreatic islets of type 1 diabetic patients, which is consistent with the possibility that a low-grade enteroviral infection in the pancreatic islets contributes to disease progression in humans.Academy of FinlandSouth-Eastern Norway Regional HealthAuthorityNovo Nordisk FoundationPEVNET (Persistent Virus Infection in Diabetes Network) Study GroupEuropean Union’s Seventh Framework ProgrammeSwedish Medical Research CouncilDiabetes Wellness FoundationJDR

Evidence for modulation of pericryptal sheath myofibroblasts in rat descending colon by Transforming Growth Factor β and Angiotensin II.

BACKGROUND: Absorption of water and Na(+) in descending colonic crypts is dependent on the barrier function of the surrounding myofibroblastic pericryptal sheath. Here the effects of high and low Na(+) diets and exposure to whole body ionising radiation on the growth and activation of the descending colonic pericryptal myofibroblasts are evaluated. In addition the effect of a post-irradiation treatment with the angiotensin converting enzyme inhibitor Captopril was investigated. METHODS: The levels of Angiotensin II type 1 receptor (AT1), ACE, collagen type IV, transforming growth factor-β type 1 receptor (TGF-βR1), OB cadherin and α-smooth muscle actin in both descending colon and caecum were evaluated, using immunocytochemistry and confocal microscopy, in rats fed on high and low Na(+) diets (LS). These parameters were also determined during 3 months post-irradiation with 8Gy from a (60)Co source in the presence and absence of the angiotensin converting enzyme inhibitor, Captopril. RESULTS: Increases in AT1 receptor (135.6% ± 18.3, P < 0.001); ACE (70.1% ± 13.1, P < 0.001); collagen type IV (49.6% ± 15.3, P < 0.001); TGF-β1 receptors (291.0% ± 26.5, P < 0.001); OB-cadherin (26.3% ± 13.8, P < 0.05) and α-smooth muscle actin (82.5% ± 12.4, P < 0.001) were observed in the pericryptal myofibroblasts of the descending colon after LS diet. There are also increases in AT1 receptor and TGF-β1 receptor, smooth muscle actin and collagen type IV after irradiation. Captopril reduced all these effects of irradiation on the pericryptal sheath and also decreased the amount of collagen and smooth muscle actin in control rats (P < 0.001). CONCLUSIONS: These results demonstrate an activation of descending colonic myofibroblasts to trophic stimuli, or irradiation, which can be attenuated by Captopril, indicative of local trophic control by angiotensin II and TGF-β release

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Analysis of gene expression in the nervous system identifies key genes and novel candidates for health and disease

The incidence of neurodegenerative diseases in the developed world has risen over the last century, concomitant with an increase in average human lifespan. A major challenge is therefore to identify genes that control neuronal health and viability with a view to enhancing neuronal health during ageing and reducing the burden of neurodegeneration. Analysis of gene expression data has recently been used to infer gene functions for a range of tissues from co-expression networks. We have now applied this approach to transcriptomic datasets from the mammalian nervous system available in the public domain. We have defined the genes critical for influencing neuronal health and disease in different neurological cell types and brain regions. The functional contribution of genes in each co-expression cluster was validated using human disease and knockout mouse phenotypes, pathways and gene ontology term annotation. Additionally a number of poorly annotated genes were implicated by this approach in nervous system function. Exploiting gene expression data available in the public domain allowed us to validate key nervous system genes and, importantly, to identify additional genes with minimal functional annotation but with the same expression pattern. These genes are thus novel candidates for a role in neurological health and disease and could now be further investigated to confirm their function and regulation during ageing and neurodegeneration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10048-017-0509-5) contains supplementary material, which is available to authorized users

The Gene Ontology: enhancements for 2011

The Gene Ontology (GO) (http://www.geneontology.org) is a community bioinformatics resource that represents gene product function through the use of structured, controlled vocabularies. The number of GO annotations of gene products has increased due to curation efforts among GO Consortium (GOC) groups, including focused literature-based annotation and ortholog-based functional inference. The GO ontologies continue to expand and improve as a result of targeted ontology development, including the introduction of computable logical definitions and development of new tools for the streamlined addition of terms to the ontology. The GOC continues to support its user community through the use of e-mail lists, social media and web-based resources

Genetic architecture of human plasma lipidome and its link to cardiovascular disease

Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 x10(-8)), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD

Studio- ja konserttiliveäänitteen erot : äänittämisen, miksaamisen ja taiteellisen tuottamisen metodit ja periaatteet

Opinnäytetyöni tarkoitus oli tutkia konserttiliven taltioimisen ja studioäänittämisen, sekä näiden miksauksien eroja. Vaikka kummassakin tapauksessa on teknisesti kyse samasta asiasta, käytännön tasolla niissä on paljon eroja. Äänitteen tunnelma ja vaikutelma on sidonnainen moneen muuhunkin asiaan, kuin oikein valittuihin mikitystekniikoihin ja akustisesti ammattimaisiin tiloihin. Kirjallisessa osiossa käsittelin näiden keskenään erilaisten lähestymistapojen teknistä ja taiteellista toteutusta vaiheittain. Toin esiin paljon omia kokemuksia ja tekemisen kautta opittuja asioita, sekä hyväksi todettuja ratkaisuja. Työn mediaosuutena oli kaksi äänitettä, jotka edustavat kumpaakin työtapaa. Suurin osa kirjallisesta läpikäynnistä viittasi näihin kahteen teokseen, mutta toin esiin myös esimerkkejä aikaisemmista kokemuksistani. Kuten aluksi olin odottanutkin, työtavoissa ilmeni runsaasti teknisiä samankaltaisuuksia. Ajatusmaailman ja suhtautumistavan tärkeys kuitenkin korostui yli odotusten. Äänittäminen voi olla teknisempää kuin miksaaminen, mutta äänittäjän kyky toimia ihmisten kanssa ja tehdä kauaskantoisia ratkaisuja vaikuttaa suoraan lopullisen tuotteen laatuun. Miksaamisen olen oppinut näkemään yhä enemmän ensisijaisesti taiteellisena prosessina, kuin teknisenä toteuttamisena.The aim of this study was to investigate the differences in the recording and mixing of live and studio performances. From the technical perspective, both seem to be very similar but there are major differences underneath. The feeling and atmosphere in a recording are bound to a variety of aspects, rather than only being a technical process combined with professional recording facilities. The literary part of this study was to elaborate the differences of these two perspectives from a technical and artistic point of view. The thesis introduced many personal experiences of the subject, matters that I have learnt by doing and various practical solutions well proven. The media part consisted of two stereo recordings that I have made representing two different styles of recording. Most of the literary part referred to these two recordings, but some examples of my earlier experiences were also brought forth. As expected, there were many technical similarities between the two methods. However, the importance of thinking and finding the most suitable point of view to the project was emphasized. The recording process might be more technical than mixing, but the ability to co-operate and to make far-reaching decisions is an important feature for a recorder to be harnessed to directly affect the quality of the final product. I have learnt to consider mixing more as a creative process than technical labor

Purification of Fungal High Molecular Weight Genomic DNA from Environmental Samples

Sequencing of a high number of fungal genomes has become possible due to the development of next generation sequencing techniques (NGS).The most recent developments aim to sequence single-molecule long-reads in order to improve genome assemblies, but consequently needs higher quality (minimum >20 kbp) DNA as starting material.However, environmental-derived samples from soil, wood, or litter often contain phenolic compounds, pigments, and other molecules that can be inhibitors for reactions during sequencing library construction.In this chapter, we propose an optimized protocol allowing the preparation of high quality and long fragment DNA from different samples (mycelium, fruiting body, soil) compatible with the current sequencing requirements