Behavioural data on the production of males by workers in the stingless bee Melipona favosa (Apidae, Meliponinae)

Male production was studied in four queenright M. favosa colonies by permanent and long duration observation of egg-laying and subsequent bee emergence. Workers produced males in all colonies; they produced 94.5% of all males

Type I IFN signature in childhood-onset systemic lupus erythematosus: A conspiracy of DNA- and RNA-sensing receptors?

Background: Childhood-onset systemic lupus erythematosus (cSLE) is an incurable multi-systemic autoimmune disease. Interferon type I (IFN-I) plays a pivotal role in the pathogenesis of SLE. The objective of this study was to assess the prevalence of the IFN-I signature and the contribution of cytosolic nucleic acid receptors to IFN-I activation in a cohort of primarily white cSLE patients. Methods: The IFN-I score (positive or negative), as a measure of IFN-I activation, was assessed using real-time quantitative PCR (RT-PCR) expression values of IFN-I signature genes (IFI44, IFI44L, IFIT1, Ly6e, MxA, IFITM1) in CD14+ monocytes of cSLE patients and healthy controls (HCs). Innate immune receptor expression was determined by RT-PCR and flow cytometry. To clarify the contribution of RNA-binding RIG-like receptors (RLRs) and DNA-binding receptors (DBRs) to IFN-I activation, peripheral blood mononuclear cells (PBMCs) from patients were treated with BX795, a TANK-binding kinase 1 (TBK1) inhibitor blocking RLR and DBR pathways. Results: The IFN-I signature was positive in 57% of cSLE patients and 15% of the HCs. Upregulated gene expression of TLR7, RLRs (IFIH1, DDX58, DDX60, DHX58) and DBRs (ZBP-1, IFI16) was observed in CD14+ monocytes of the IFN-I-positive cSLE patients. Additionally, RIG-I and ZBP-1 protein expression was upregulated in these cells. Spontaneous IFN-I stimulated gene (ISG) expression in PBMCs from cSLE patients was inhibited by a TBK1-blocker. Conclusions: IFN-I activation, assessed as ISG expression, in cSLE is associated with increased expression of TLR7, and RNA and DNA binding receptors, and these receptors contribute to IFN-I activation via TBK1 signaling. TBK1-blockers may therefore be a promising treatment target for SLE

Preeclampsia and coronary plaque erosion: Manifestations of endothelial dysfunction resulting in cardiovascular events in women

Therapeutic cell differentiatio

Efficacy of Baricitinib in the Treatment of Chilblains Associated With Aicardi-Goutieres Syndrome, a Type I Interferonopathy

Genetics of disease, diagnosis and treatmen

Arbokennisinfrastructuur in de call center branche

In dit TNO-rapport staat de arbokennisinfrastructuur rond RSI-knelpunten bij beeldschermarbeid in de call centers centraal. Op basis van een literatuurverkenning, een workshop met betrokkenen uit de arbokennisinfrastructuur, telefoongesprekken voorafgaand aan deze workshop én vier ingevulde vragenlijsten van genodigden voor deze workshop wordt geprobeerd een beeld te schetsen van deze arbokennisinfrastructuur en het functioneren daarvan

Stand der techniek in de GGZ integraal onderzocht : maatregelen ter reductie van fysieke belasting, psychosociale belasting, agressie en onveiligheid

Dit onderzoek geeft een overzicht van de stand der techniek te geven ten aanzien van de volgende arbeidsrisicogebieden in de geestelijke gezondheidszorg (GGZ): de fysieke belasting, de psychosociale belasting, agressie en onveiligheid in GGZ-instellingen, en in het bijzonder agressie en onveiligheid in crisisdiensten en verslavingszorg. Het onderzoek vond plaats in het kader van de voorbereiding voor een arboconvenant in de GGZ. Het doel van het onderzoek was te bepalen welke oplossingen en maatregelen binnen de GGZ gehanteerd kunnen worden om de mate van blootstelling aan fysieke en psychosociale belasting, alsmede agressie en onveiligheid terug te dringen. Het onderzoek heeft door middel van een zogenaamde contextanalyse en observaties (fysieke belasting) eerst in kaart gebracht waaruit de blootstelling bestaat en hoe het problematisch instellingen en hun medewerkers dat ervaren. Op basis van literatuuronderzoek, secundaire analyses van bestaande gegevensbestanden, werkbezoeken aan koploperinstellingen, metingen en een werkconferentie is een overzicht tot stand gekomen van aanbevolen maatregelen voor de convenantpartijen in GGZ. Onderzoek verricht in opdracht van het ministerie van Sociale Zaken en Werkgelegenheid door TNO Arbei

Extranodal marginal zone lymphoma clonotypes are detectable prior to eMZL diagnosis in tissue biopsies and peripheral blood of Sjögren's syndrome patients through immunogenetics.

INTRODUCTION: Activated B cells play a key role in the pathogenesis of primary Sjögren's syndrome (pSS) through the production of autoantibodies and the development of ectopic germinal centers in the salivary glands and other affected sites. Around 5-10% of pSS patients develop B-cell lymphoma, usually extranodal marginal zone lymphomas (eMZL) of the mucosa-associated lymphoid tissue (MALT). The aim of the current study is to investigate if the eMZL clonotype is detectable in prediagnostic blood and tissue biopsies of pSS patients. METHODS/RESULTS: We studied prediagnostic tissue biopsies of three pSS patients diagnosed with eMZL and four pSS controls through immunoglobulin (IG) gene repertoire sequencing. In all three cases, we observed the eMZL clonotype in prediagnostic tissue biopsies. Among controls, we observed transient elevation of clonotypes in two pSS patients. To evaluate if eMZL clonotypes may also be detected in the circulation, we sequenced a peripheral blood mononuclear cell (PBMC) sample drawn at eMZL diagnosis and two years prior to eMZL relapse in two pSS patients. The eMZL clonotype was detected in the peripheral blood prior to diagnosis in both cases. Next, we selected three pSS patients who developed eMZL lymphoma and five additional pSS patients who remained lymphoma-free. We sequenced the IG heavy chain (IGH) gene repertoire in PBMC samples taken a median of three years before eMZL diagnosis. In two out of three eMZL patients, the dominant clonotype in the prediagnostic PBMC samples matched the eMZL clonotype in the diagnostic biopsy. The eMZL clonotypes observed consisted of stereotypic IGHV gene combinations (IGHV1-69/IGHJ4 and IGHV4-59/IGHJ5) associated with rheumatoid factor activity, a previously reported feature of eMZL in pSS. DISCUSSION: In conclusion, our results indicate that eMZL clonotypes in pSS patients are detectable prior to overt eMZL diagnosis in both tissue biopsies and peripheral blood through immunogenetic sequencing, paving the way for the development of improved methods of early detection of eMZL

Gene signature fingerprints stratify SLE patients in groups with similar biological disease profiles: a multicentre longitudinal study

OBJECTIVES: Clinical phenotyping and predicting treatment responses in SLE patients is challenging. Extensive blood transcriptional profiling has identified various gene modules that are promising for stratification of SLE patients. We aimed to translate existing transcriptomic data into simpler gene signatures suitable for daily clinical practice. METHODS: Real-time PCR of multiple genes from the IFN M1.2, IFN M5.12, neutrophil (NPh) and plasma cell (PLC) modules, followed by a principle component analysis, was used to identify indicator genes per gene signature. Gene signatures were measured in longitudinal samples from two childhood-onset SLE cohorts (n = 101 and n = 34, respectively), and associations with clinical features were assessed. Disease activity was measured using Safety of Estrogen in Lupus National Assessment (SELENA)-SLEDAI. Cluster analysis subdivided patients into three mutually exclusive fingerprint-groups termed (1) all-signatures-low, (2) only IFN high (M1.2 and/or M5.12) and (3) high NPh and/or PLC. RESULTS: All gene signatures were significantly associated with disease activity in cross-sectionally collected samples. The PLC-signature showed the highest association with disease activity. Interestingly, in longitudinally collected samples, the PLC-signature was associated with disease activity and showed a decrease over time. When patients were divided into fingerprints, the highest disease activity was observed in the high NPh and/or PLC group. The lowest disease activity was observed in the all-signatures-low group. The same distribution was reproduced in samples from an independent SLE cohort. CONCLUSIONS: The identified gene signatures were associated with disease activity and were indicated to be suitable tools for stratifying SLE patients into groups with similar activated immune pathways that may guide future treatment choices