CD20(+) T cells have a predominantly Tc1 effector memory phenotype and are expanded in the ascites of patients with ovarian cancer.

Copyright © 2015 Taylor & Francis Group, LLCRecently, a small subset of T cells that expresses the B cell marker CD20 has been identified in healthy volunteers and in patients with rheumatoid arthritis and multiple sclerosis. The origin of these CD20-positive T cells as well as their relevance in human disease remains unclear. Here, we identified that after functional B cell/T cell interaction CD20 molecules are transferred to the cell surface of T cells by trogocytosis together with the established trogocytosis marker HLA-DR. Further, the presence of CD20 on isolated CD20(+) T cells remained stable for up to 48h of ex vivo culture. These CD20(+) T cells almost exclusively produced IFNγ (∼70% vs. ∼20% in the CD20(-) T cell population) and were predominantly (CD8(+)) effector memory T cells (∼60-70%). This IFNγ producing and effector memory phenotype was also determined for CD20(+) T cells as detected in the peripheral blood and ascitic fluids of ovarian cancer (OC) patients. In the latter, the percentage of CD20(+) T cells was further strongly increased (from ∼6% in peripheral blood to 23% in ascitic fluid). Taken together, the data presented here indicate that CD20 is transferred to T cells upon intimate T cell/B cell interaction. Further, CD20(+) T cells are of memory and IFNγ producing phenotype and are present in increased amounts in ascitic fluid of OC patients.Netherlands Organization for Scientific ResearchDutch Cancer SocietyAlexander von Humboldt Foundatio

Response of Methicillin-Resistant Staphylococcus aureus to Amicoumacin A

Amicoumacin A exhibits strong antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), hence we sought to uncover its mechanism of action. Genome-wide transcriptome analysis of S. aureus COL in response to amicoumacin A showed alteration in transcription of genes specifying several cellular processes including cell envelope turnover, cross-membrane transport, virulence, metabolism, and general stress response. The most highly induced gene was lrgA, encoding an antiholin-like product, which is induced in cells undergoing a collapse of Δψ. Consistent with the notion that LrgA modulates murein hydrolase activity, COL grown in the presence of amicoumacin A showed reduced autolysis, which was primarily caused by lower hydrolase activity. To gain further insight into the mechanism of action of amicoumacin A, a whole genome comparison of wild-type COL and amicoumacin A-resistant mutants isolated by a serial passage method was carried out. Single point mutations generating codon substitutions were uncovered in ksgA (encoding RNA dimethyltransferase), fusA (elongation factor G), dnaG (primase), lacD (tagatose 1,6-bisphosphate aldolase), and SACOL0611 (a putative glycosyl transferase). The codon substitutions in EF-G that cause amicoumacin A resistance and fusidic acid resistance reside in separate domains and do not bring about cross resistance. Taken together, these results suggest that amicoumacin A might cause perturbation of the cell membrane and lead to energy dissipation. Decreased rates of cellular metabolism including protein synthesis and DNA replication in resistant strains might allow cells to compensate for membrane dysfunction and thus increase cell survivability

A Review on the Mechanical Modeling of Composite Manufacturing Processes

© 2016, The Author(s). The increased usage of fiber reinforced polymer composites in load bearing applications requires a detailed understanding of the process induced residual stresses and their effect on the shape distortions. This is utmost necessary in order to have more reliable composite manufacturing since the residual stresses alter the internal stress level of the composite part during the service life and the residual shape distortions may lead to not meeting the desired geometrical tolerances. The occurrence of residual stresses during the manufacturing process inherently contains diverse interactions between the involved physical phenomena mainly related to material flow, heat transfer and polymerization or crystallization. Development of numerical process models is required for virtual design and optimization of the composite manufacturing process which avoids the expensive trial-and-error based approaches. The process models as well as applications focusing on the prediction of residual stresses and shape distortions taking place in composite manufacturing are discussed in this study. The applications on both thermoset and thermoplastic based composites are reviewed in detail

Suicide among persons with childhood leukaemia in Slovenia

Pri osebah, ki so v otroštvu zbolele za rakom, so pogosto prisotne telesne in psihosocialne posledice bolezni ter njenega zdravljenja. Mnoge raziskave so pokazale, da je pri osebah z izkušnjo raka v otroštvu depresivnost in samomorilno vedenje močneje izraženo. V naši raziskavi smo proučili pojavljanje samomorov pri osebah, ki so v otroštvu zbolele za levkemijo, v primerjavi s splošno populacijo v Sloveniji, v obdobju 1978–2010. Pričakovano število samomorov smo izračunali na osnovi kontrolne skupine posameznikov iz splošne populacije, ki je bila s skupino preiskovancev, tj. oseb, ki so v otroštvu zbolele za levkemijo, izenačena po spolu, starosti ob začetku opazovanja, letu začetka opazovanja in dolžini opazovanja. Raziskava je pokazala, da med tistimi, ki so v otroštvu zboleli za levkemijo, v letih 1978–2010 nobena oseba ni storila samomora, kar se statistično značilno ne razlikuje od pričakovanega števila samomorov (0,448) v primerljivi splošni populaciji v Sloveniji. Ugotovitve raziskave nakazujejo, da kljub znano bolj izraženem samomorilnem vedenju med preživelimi raka v otroštvu v Sloveniji v primerjavi s splošno populacijo pojavljanje samomorov pri osebah, zbolelih za levkemijo v otroštvu, ni pogostejše kot v splošni populaciji.Persons with childhood leukaemia often suffer from physical and psychosocial consequences of the disease and its treatment. Several studies have shown that depression and suicidal behaviour are expressed strongly in persons with a childhood cancer experience. In our study, we researched the occurrence of suicides among persons with childhood leukaemia compared to the general population in Slovenia in the period 1978–2010. The expected number of suicides was calculated based on the control group of individuals from the general population with the same gender, age at the beginning of observation, starting year and duration of observation as the research group, thus group of persons with childhood cancer. The study showed that none of the persons with childhood cancer committed suicide in the period 1978-2010, which is not statistically different from the expected number of suicides (0.448) in comparison with the general population in Slovenia. The findings of this study indicate that, despite the significantly increased expression of suicidal behaviour among survivors of childhood leukaemia in Slovenia compared to the general population, suicides do not occur more often among people with childhood leukaemia than among the general population

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Methods to analyse phytoplankton: a manual for a thematic approach

Er is een toenemend aantal methoden voor fytoplanktonanalyse voor monitoring en onderzoek van de waterkwaliteit. Naarmate deze methoden technisch ingewikkelder zijn, wordt het moeilijker de werking en de specifieke sterke en zwakke eigenschappen te kennen. Geen van de methoden is beter dan de anderen. Daarom moet een rationele keuze gebaseerd zijn op kennis van de technologie en eigenschappen van de methoden. De handleiding geeft een projectleider voldoende kennis van de vijf meest gebruikte methoden om een keuze te doen, die aansluit bij het doel en de logistieke en financiele randvoorwaarden van het zijn project. De behandelde methoden zijn: remote sensing, flowcytometrie, high performance chromatography, chlorofyl extractie en lichtmicroscopie. Een systematische aanpak wordt voorgesteld om voor een bepaald project te kiezen voor een daarbij horende methode. De aanpak is gebaseerd op de fytoplanktoneigenschappen, die moeten worden geanalyseerd en op de logistieke randvoorwaarden van het project. Tevens wordt inzicht gegeven in de financiele consequenties van een keuze. Enkele fictieve voorbeelden illustreren dat een combinatie van methoden vaak het optimale resultaat oplevert.There is an increasing array of methods for analysing phytoplankton analysis for aquatic research and monitoring projects. As these methods are technologically more advanced they become more difficult to comprehend and to acknowledge their specific strongpoints and weaknesses. Since no single method is generally superior to other methods a rational selection based on a general understanding of the technology and characteristics of the methods should be made. The manual should provide a project manager with adequate knowledge on the main methods of analysis for making a selection which suits the objectives and the logistics, as well as the financial restrictions of his/her project. The manual gives an overview of the five most common methods: remote sensing, flow cytometry, high performance liquid chromatography, chlorophyll extraction and light microscopy. A systematic approach is presented for selecting a method based on the phytoplankton characteristics to be analysed within a specific project and providing insight into the financial consequences. Examples from fictitious projects illustrate that a combination of methods will often provide an optimal result.DGM/DWL Ministerie voor Rijkswaterstaat (RIZA

Ethnic Identity and the Risk of Schizophrenia in Ethnic Minorities: A Case-Control Study

Objectives: The high incidence of schizophrenia in immigrant ethnic groups in Western Europe may be explained by social stress associated with ethnic minority status. Positive identification with one's own ethnic group is a strong predictor of mental health in immigrants. We investigated whether negative ethnic identity is related to schizophrenia risk in non-Western immigrants. Methods: Matched case-control study of first-episode schizophrenia, including 100 non-Western immigrant cases, general hospital controls (n = 100), and siblings (n = 63). Conditional logistic regression analyses were used to investigate associations between schizophrenia and ethnic group identity. Results: Cases had a negative ethnic identity more often than general hospital controls (64% and 35%, respectively, P < .001). After adjustment for marital status, level of education, unemployment, self-esteem, social support, and cannabis use, negative ethnic identity was associated with schizophrenia: odds ratio = 3.29; 95% confidence interval = 1.36-7.92. Cases significantly more often had an assimilated or a marginalized identity and less often had a separated identity. Comparisons between cases and siblings largely confirmed these findings. Conclusions: Negative identification with the own ethnic group may be a risk factor for schizophrenia in immigrants living in a context of social adversity