Retained NK cell phenotype and functionality in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD), and the progressive stage non-alcoholic steatohepatitis (NASH), is the predominant cause of chronic liver disease globally. As part of the complex pathogenesis, natural killer (NK) cells have been implicated in the development of liver inflammation in experimental murine models of NASH. However, there is a lack of knowledge on how NK cells are affected in humans with this disease. Here, we explored the presence of disease-specific changes within circulating and tissue-resident NK cell populations, as well as within other major immune cell subsets, in patients with liver biopsy-confirmed NAFLD. Using 18-color-flow cytometry, substantial changes were observed in certain myeloid populations in patients as compared to controls. NK cell numbers, on the other hand, were not altered. Furthermore, only minor differences in expression of activating and inhibitory NK cell receptors were noted, with the exception of an increased expression of NKG2D on NK cells from patients with NASH. NK cell differentiation remained constant, and NK cells from these patients retain their ability to respond adequately upon stimulation. Instead, considerable alterations were observed between liver, adipose tissue, and peripheral blood NK cells, independently of disease status. Taken together, these results increase our understanding of the importance of the local microenvironment in shaping the NK cell compartment and stress the need for further studies exploring how NASH affects intrahepatic NK cells in humans.publishedVersio

Metaxa2 Database Builder: enabling taxonomic identification from metagenomic or metabarcoding data using any genetic marker

Motivation: Correct taxonomic identification of DNA sequences is central to studies of biodiversity using both shotgun metagenomic and metabarcoding approaches. However, no genetic marker gives sufficient performance across all the biological kingdoms, hampering studies of taxonomic diversity in many groups of organisms. This has led to the adoption of a range of genetic markers for DNA metabarcoding. While many taxonomic classification software tools can be re-trained on these genetic markers, they are often designed with assumptions that impair their utility on genes other than the SSU and LSU rRNA. Here, we present an update to Metaxa2 that enables the use of any genetic marker for taxonomic classification of metagenome and amplicon sequence data. Results: We evaluated the Metaxa2 Database Builder on 11 commonly used barcoding regions and found that while there are wide differences in performance between different genetic markers, our software performs satisfactorily provided that the input taxonomy and sequence data are of high quality. Availability and implementation: Freely available on the web as part of the Metaxa2 package at http://microbiology.se/software/metaxa2/. Supplementary information: Supplementary data are available at Bioinformatics online

A systematic review of randomised controlled trials on the effectiveness of exercise programs on lumbo pelvic pain among postnatal women

Background: A substantial number of women tend to be affected by Lumbo Pelvic Pain (LPP) following child birth. Physical exercise is indicated as a beneficial method to relieve LPP, but individual studies appear to suggest mixed findings about its effectiveness. This systematic review aimed to synthesise evidence from randomised controlled trials on the effectiveness of exercise on LPP among postnatal women to inform policy, practice and future research. Methods: A systematic review was conducted of all randomised controlled trials published between January 1990 and July 2014, identified through a comprehensive search of following databases: PubMed, PEDro, Embase, Cinahl, Medline, SPORTDiscus, Cochrane Pregnancy and Childbirth Group’s Trials Register, and electronic libraries of authors’institutions. Randomised controlled trials were eligible for inclusion if the intervention comprised of postnatal exercise for women with LPP onset during pregnancy or within 3 months after delivery and the outcome measures included changes in LPP. Selected articles were assessed using the PEDro Scale for methodological quality and findings were synthesised narratively as meta-analysis was found to be inappropriate due to heterogeneity among included studies. Results: Four randomised controlled trials were included, involving 251 postnatal women. Three trials were rated as of ‘good’ methodological quality. All trials, except one, were at low risk of bias. The trials included physical exercise programs with varying components, differing modes of delivery, follow up times and outcome measures. Intervention in one trial, involving physical therapy with specific stabilising exercises, proved to be effective in reducing LPP intensity. An improvement in gluteal pain on the right side was reported in another trial and a significant difference in pain frequency in another. Conclusion: Our review indicates that only few randomised controlled trials have evaluated the effectiveness of exercise on LPP among postnatal women. There is also a great amount of variability across existing trials in the components of exercise programs, modes of delivery, follow up times and outcome measures. While there is some evidence to indicate the effectiveness of exercise for relieving LPP, further good quality trials are needed to ascertain the most effective elements of postnatal exercise programs suited for LPP treatment

Microbial respiration with chlorine oxyanions: diversity and physiological and biochemical properties of chlorate- and perchlorate-reducing microorganisms

Chlorine oxyanions are valuable electron acceptors for microorganisms. Recent findings have shed light on the natural formation of chlorine oxyanions in the environment. These suggest a permanent introduction of respective compounds on Earth, long before their anthropogenic manufacture. Microorganisms that are able to grow by the reduction of chlorate and perchlorate are affiliated with phylogenetically diverse lineages, spanning from the Proteobacteria to the Firmicutes and archaeal microorganisms. Microbial reduction of chlorine oxyanions can be found in diverse environments and different environmental conditions (temperature, salinities, pH). It commonly involves the enzymes perchlorate reductase (Pcr) or chlorate reductase (Clr) and chlorite dismutase (Cld). Horizontal gene transfer seems to play an important role for the acquisition of functional genes. Novel and efficient Clds were isolated from microorganisms incapable of growing on chlorine oxyanions. Archaea seem to use a periplasmic Nar-type reductase (pNar) for perchlorate reduction and lack a functional Cld. Chlorite is possibly eliminated by alternative (abiotic) reactions. This was already demonstrated for Archaeoglobus fulgidus, which uses reduced sulfur compounds to detoxify chlorite. A broad biochemical diversity of the trait, its environmental dispersal, and the occurrence of relevant enzymes in diverse lineages may indicate early adaptations of life toward chlorine oxyanions on Earth.Financial support from the Technology Foundation STW, Applied Science Division of the Netherlands Science Foundation NWO (Project 08053) and Shell Global Solutions International BV. Research of A.J.M. Stams is financed by an ERC grant (Project 323009) and by a Gravitation grant (Project 024.002.002) from the Netherlands Ministry of Education, Culture, and Scienc

Verification of genes differentially expressed in neuroblastoma tumours: a study of potential tumour suppressor genes

<p>Abstract</p> <p>Background</p> <p>One of the most striking features of the childhood malignancy neuroblastoma (NB) is its clinical heterogeneity. Although there is a great need for better clinical and biological markers to distinguish between tumours with different severity and to improve treatment, no clear-cut prognostic factors have been found. Also, no major NB tumour suppressor genes have been identified.</p> <p>Methods</p> <p>In this study we performed expression analysis by quantitative real-time PCR (QPCR) on primary NB tumours divided into two groups, of favourable and unfavourable outcome respectively. Candidate genes were selected on basis of lower expression in unfavourable tumour types compared to favourables in our microarray expression analysis. Selected genes were studied in two steps: (1) using TaqMan Low Density Arrays (TLDA) targeting 89 genes on a set of 12 NB tumour samples, and (2) 12 genes were selected from the TLDA analysis for verification using individual TaqMan assays in a new set of 13 NB tumour samples.</p> <p>Results</p> <p>By TLDA analysis, 81 out of 87 genes were found to be significantly differentially expressed between groups, of which 14 have previously been reported as having an altered gene expression in NB. In the second verification round, seven out of 12 transcripts showed significantly lower expression in unfavourable NB tumours, <it>ATBF1</it>, <it>CACNA2D3</it>, <it>CNTNAP2</it>, <it>FUSIP1</it>, <it>GNB1</it>, <it>SLC35E2</it>, and <it>TFAP2B</it>. The gene that showed the highest fold change in the TLDA analysis, <it>POU4F2</it>, was investigated for epigenetic changes (CpG methylation) and mutations in order to explore the cause of the differential expression. Moreover, the fragile site gene <it>CNTNAP2 </it>that showed the largest fold change in verification group 2 was investigated for structural aberrations by copy number analysis. However, the analyses of <it>POU4F2 </it>and <it>CNTNAP2 </it>showed no genetic alterations that could explain a lower expression in unfavourable NB tumours.</p> <p>Conclusion</p> <p>Through two steps of verification, seven transcripts were found to significantly discriminate between favourable and unfavourable NB tumours. Four of the transcripts, <it>CACNA2D3</it>, <it>GNB1</it>, <it>SLC35E2</it>, and <it>TFAP2B</it>, have been observed in previous microarray studies, and are in this study independently verified. Our results suggest these transcripts to be markers of malignancy, which could have a potential usefulness in the clinic.</p

Utvärdering av programvara/molntjänst för framställning av ortofoton med UAS-data

Unmanned Aerial Vehicle (UAV) är en benämning på en obemannad flygande farkost. UAV är en benämning för själva farkosten och därför har Unmanned Aircraft System (UAS) tagit över eftersom det är ett begrepp som rör hela systemet som förutom flygfarkost innefattar start, landning, markstation och kommunikationslänk. Inom mätningsteknik är UAS ett relativt nytt begrepp och tekniken har sin historia mestadels inom det militära området. Syftet med denna studie är att analysera samt utvärdera två programvaror och en molntjänst för bearbetning och framtagning av ortofoto från UAS-data. De frågor som ställts inför arbetet är: kan en molntjänst ersätta ett avancerat datorprogram vid generering av ortofoton? Kan dessa datorprogram ge ett bra resultat utan hjälp av andra GIS-program? Vilket program är enklast att förstå och använda samt vilka är skillnaderna mellan programmen? Dessa frågor har besvarats genom användning av insamlat data och för att få utvärderingen rättvis har därför tre olika dataset skapats. Programtjänsterna som har utvärderats är Agisoft PhotoScan 0.9.0 och Pix4UAV Desktop/Cloud 2.1.2. Insamling av data har skett genom en flygning med en oktokopter över Fågelmyratippen i Dalarna. Resultaten visar att priset snabbt blir högt om endast Pix4UAV Cloud används och att överlag är PhotoScan billigare än Pix4UAV Desktop. Kvalitetsrapporten som följer med varje projekt är överskådlig i PhotoScan och mer ingående i Pix4UAV Desktop/Cloud. Trots samma indata blir utdatat olika vid bearbetning av de olika programmen, till exempel skiljer sig markupplösningen åt mellan programmen. Generellt är PhotoScan tydligare på att visa hur arbetsprocessen går till. Supporten hos båda företagen är bra, tips och tricks finns på respektive hemsida. Till PhotoScan finns även en manual för nedladdning samt en YouTube-kanal med instruktionsvideor. De enda slutsatserna vi drar är att Pix4UAV Cloud inte klarar av att ersätta ett avancerat bildbehandlingsprogram och att för tillfället bör ytterligare ett GIS-program användas som komplement för att få bästa resultat. I övrigt har vi endast skrapat på ytan av programmen och rekommenderar att läsaren tar till sig det vi skrivit under resultat och diskussion för att sedan bilda sig en egen uppfattning med hjälp av respektive programs prövotid. Till sist presenteras förslag på vidare studier inom ämnet.Unmanned Aerial Vehicle (UAV) is a term for a remote controlled airbornevehicle. Since UAV is an acronym for the vehicle itself, Unmanned Aircraft Systems(UAS) has therefore replaced UAV, as it is a concept related to the wholesystem, beside the vehicle it also includes landing, ground station andcommunications link. Within land surveying UAS is a relatively new concept asthe technology has its history mainly associated to the military. The purposeof this study is to analyze and evaluate two software and a cloud service for processingand preparation of orthophotos from data collected with a UAS. The questions tobe answered in this thesis are: Can a cloud service replace an advancedcomputer software for generating orthophotos? Can these produce good resultswithout the help of other GIS software? Which software is the easiest tounderstand and to use and what are the main differences. These questions wereanswered by using collected data, and to get the evaluation fair three datasetshave been created. The software being evaluated are Agisoft PhotoScan andPix4UAV desktop/cloud. The data collection was done by a flight with an octokopterover Fågelmyratippen in Dalarna. The results show that the price quicklybecomes high if only Pix4UAV Cloud is used and that generally PhotoScan ischeaper than Pix4UAV Desktop. The quality report that comes with each projectis easy to understand in PhotoScan but more detailed in Pix4UAV Desktop/Cloud. Despitethe use of same data the results vary when processed, for example the groundresolution. Generally PhotoScan is better at showing the work process. Eachcompany’s support is good and they both have tips and tricks at their websites.On the Agisoft webpage there is a manual available for download and they alsohave a YouTube-channel with instruction videos. The conclusion is that thecloud service is not capable of replacing an advance image processing software.Another conclusion is that for the moment another GIS-program should be used toget the best results. We like to point out that we only scratched the surfaceof the software and we recommend that the reader embrace what we write inresults and discussion to then form their own opinion by using the softwareevaluation period. I the last part we present subjects of further study