Gene induction during differentiation of human monocytes into dendritic cells: an integrated study at the RNA and protein levels

Changes in gene expression occurring during differentiation of human monocytes into dendritic cells were studied at the RNA and protein levels. These studies showed the induction of several gene classes corresponding to various biological functions. These functions encompass antigen processing and presentation, cytoskeleton, cell signalling and signal transduction, but also an increase in mitochondrial function and in the protein synthesis machinery, including some, but not all, chaperones. These changes put in perspective the events occurring during this differentiation process. On a more technical point, it appears that the studies carried out at the RNA and protein levels are highly complementary.Comment: website publisher: http://www.springerlink.com/content/ha0d2c351qhjhjdm

Evaluation of cowpea accessions for resistance to flower bud thrips (Megalurothrips sjostedti) in Mali

Open Access JournalFlower bud thrips (Megalurothrips sjostedti) is one of the most damaging pests to cowpea in Africa and varietal resistance is one of the effective approaches to minimize the pest damage. Study was conducted to assess variability among 117 genotypes in addition to two resistant (Sanzisabinli and TVu 1509) and one susceptible (Vita7) checks at Cinzana and N’Tarla locations under natural and artificial infestations of thrips. Parameters such as total number of pods per plant and damage scoring were used to assess the test entries. Genotypes CIPEA82672, Suivita2, TVu 1509 and Sanzisabinli were found highly tolerant, Diaye and TVu7677 moderately tolerant whilst nine genotypes were found tolerant to thrips attacks. CIPEA82672 and Suivita2 had higher grain yield than the resistant checks. Year by genotype, year by location and year by location by genotype interactions were significant for most traits. Genotype by genotype by environment (GGE) effect on yield showed CIPEA82672 most stable across both locations while Suivita2 was only stable at N’Tarla. High broad sense heritability (H2b) was observed for some traits such as damage scoring across locations. Highest genotypic coefficient of variation (GCV) of 81.24 and phenotypic coefficient of variation (PCV) of 75.62 were attributed to total number of pods per plant. Positive correlations were detected between the damage scoring and the number of adult thrips from Cinzana (R2= 0.264) and N’Tarla (R2= 0.603) locations. Confirmation of identified cowpea genotypes highly and moderately tolerant to thrips attacks could be used to improve farmers’ preferred cowpea genotypes susceptible to thrips

Evaluation of cowpea accessions for resistance to flower bud thrips (Megalurothrips sjostedti) in Mali

Open Access JournalFlower bud thrips (Megalurothrips sjostedti) is one of the most damaging pests to cowpea in Africa and varietal resistance is one of the effective approaches to minimize the pest damage. Study was conducted to assess variability among 117 genotypes in addition to two resistant (Sanzisabinli and TVu 1509) and one susceptible (Vita7) checks at Cinzana and N’Tarla locations under natural and artificial infestations of thrips. Parameters such as total number of pods per plant and damage scoring were used to assess the test entries. Genotypes CIPEA82672, Suivita2, TVu 1509 and Sanzisabinli were found highly tolerant, Diaye and TVu7677 moderately tolerant whilst nine genotypes were found tolerant to thrips attacks. CIPEA82672 and Suivita2 had higher grain yield than the resistant checks. Year by genotype, year by location and year by location by genotype interactions were significant for most traits. Genotype by genotype by environment (GGE) effect on yield showed CIPEA82672 most stable across both locations while Suivita2 was only stable at N’Tarla. High broad sense heritability (H2b) was observed for some traits such as damage scoring across locations. Highest genotypic coefficient of variation (GCV) of 81.24 and phenotypic coefficient of variation (PCV) of 75.62 were attributed to total number of pods per plant. Positive correlations were detected between the damage scoring and the number of adult thrips from Cinzana (R2= 0.264) and N’Tarla (R2= 0.603) locations. Confirmation of identified cowpea genotypes highly and moderately tolerant to thrips attacks could be used to improve farmers’ preferred cowpea genotypes susceptible to thrips

Phenotypic Studies of Natural Killer Cell Subsets in Human Transporter Associated with Antigen Processing Deficiency

Peripheral blood natural killer (NK) cells from patients with transporter associated with antigen processing (TAP) deficiency are hyporesponsive. The mechanism of this defect is unknown, but the phenotype of TAP-deficient NK cells is almost normal. However, we noticed a high percentage of CD56bright cells among total NK cells from two patients. We further investigated TAP-deficient NK cells in these patients and compared them to NK cells from two other TAP-deficient patients with no clinical symptoms and to individuals with chronic inflammatory diseases other than TAP deficiency (chronic lung diseases or vasculitis). Peripheral blood mononuclear cells isolated from venous blood were stained with fluorochrome-conjugated antibodies and the phenotype of NK cells was analyzed by flow cytometry. In addition, 51Chromium release assays were performed to assess the cytotoxic activity of NK cells. In the symptomatic patients, CD56bright NK cells represented 28% and 45%, respectively, of all NK cells (higher than in healthy donors). The patients also displayed a higher percentage of CD56dimCD16− NK cells than controls. Interestingly, this unusual NK cell subtype distribution was not found in the two asymptomatic TAP-deficient cases, but was instead present in several of the other patients. Over-expression of the inhibitory receptor CD94/NKG2A by TAP-deficient NK cells was confirmed and extended to the inhibitory receptor ILT2 (CD85j). These inhibitory receptors were not involved in regulating the cytotoxicity of TAP-deficient NK cells. We conclude that expansion of the CD56bright NK cell subtype in peripheral blood is not a hallmark of TAP deficiency, but can be found in other diseases as well. This might reflect a reaction of the immune system to pathologic conditions. It could be interesting to investigate the relative distribution of NK cell subsets in various respiratory and autoimmune diseases

Platelet FcγRIIA-induced serotonin release exacerbates the severity of Transfusion-Related Acute Lung Injury in mice

Transfusion-related acute lung injury (TRALI) remains a major cause of transfusion-related fatalities. The mechanism of human antibody-mediated TRALI, especially the involvement of the Fcγ receptors, is not clearly established. Contrary to mice, human platelets are unique in their expression of the FcγRIIA/CD32A receptor, suggesting that our understanding of the pathogenesis of antibody-mediated TRALI is partial, as the current murine models incompletely recapitulate the human immunology. We evaluated the role of FcγRIIA/CD32A in TRALI using a humanized mouse model expressing the FcγRIIA/CD32A receptor. When challenged with a recombinant chimeric human immunoglobulin G1/mouse anti–major histocompatibility complex class I monoclonal antibody, these mice exhibited exacerbated alveolar edema and higher mortality compared with wild-type (WT) mice. Unlike in WT mice, monocytes/macrophages in CD32A(+) mice were accessory for TRALI initiation, indicating the decisive contribution of another cell type. Platelet activation was dramatically increased in CD32A(+) animals, resulting in their increased consumption and massive release of their granule contents. Platelet depletion prevented the exacerbation of TRALI in CD32A(+) mice but did not affect TRALI in WT animals. By blocking platelet serotonin uptake with fluoxetine, we showed that the severity of TRALI in CD32A(+) mice resulted from the serotonin released by the activated platelets. Furthermore, inhibition of 5-hydroxytryptamine 2A serotonin receptor with sarpogrelate, before or after the induction of TRALI, abolished the aggravation of lung edema in CD32A(+) mice. Our findings show that platelet FcγRIIA/CD32A activation exacerbates antibody-mediated TRALI and provide a rationale for designing prophylactic and therapeutic strategies targeting the serotonin pathway to attenuate TRALI in patients

The ATP-gated P2X1 ion channel contributes to the severity of antibody-mediated Transfusion-Related Acute Lung Injury in mice

The biological responses that control the development of Transfusion-Related Acute Lung Injury (TRALI), a serious post-transfusion respiratory syndrome, still need to be clarified. Since extracellular nucleotides and their P2 receptors participate in inflammatory processes as well as in cellular responses to stress, we investigated the role of the ATP-gated P2X1 cation channel in antibody-mediated TRALI. The effects of NF449, a selective P2X1 receptor (P2RX1) antagonist, were analyzed in a mouse two-hit model of TRALI. Mice were primed with lipopolysaccharide (LPS) and 24 h later challenged by administrating an anti-MHC I antibody. The selective P2RX1 antagonist NF449 was administrated before the administration of LPS and/or the anti-MHC I antibody. When given before antibody administration, NF449 improved survival while maximal protection was achieved when NF449 was also administrated before the sensitization step. Under this later condition, protein contents in bronchoalveolar lavages were dramatically reduced. Cell depletion experiments indicated that monocytes/macrophages, but not neutrophils, contribute to this effect. In addition, the reduced lung periarteriolar interstitial edemas in NF449-treated mice suggested that P2RX1 from arteriolar smooth muscle cells could represent a target of NF449. Accordingly, inhibition of TRPC6, another cation channel expressed by smooth muscle cells, also reduced TRALI-associated pulmonary interstitial and alveolar edemas. These data strongly suggest that cation channels like P2RX1 or TRPC6 participate to TRALI pathological responses

Quantum Symmetries and Strong Haagerup Inequalities

In this paper, we consider families of operators $\{x_r\}_{r \in \Lambda}$ in a tracial C$^\ast$-probability space $(\mathcal A, \phi)$, whose joint $\ast$-distribution is invariant under free complexification and the action of the hyperoctahedral quantum groups $\{H_n^+\}_{n \in \N}$. We prove a strong form of Haagerup's inequality for the non-self-adjoint operator algebra $\mathcal B$ generated by $\{x_r\}_{r \in \Lambda}$, which generalizes the strong Haagerup inequalities for $\ast$-free R-diagonal families obtained by Kemp-Speicher \cite{KeSp}. As an application of our result, we show that $\mathcal B$ always has the metric approximation property (MAP). We also apply our techniques to study the reduced C$^\ast$-algebra of the free unitary quantum group $U_n^+$. We show that the non-self-adjoint subalgebra $\mathcal B_n$ generated by the matrix elements of the fundamental corepresentation of $U_n^+$ has the MAP. Additionally, we prove a strong Haagerup inequality for $\mathcal B_n$, which improves on the estimates given by Vergnioux's property RD \cite{Ve}

The Use and Effectiveness of an Online Diagnostic Support System for Blood Film Interpretation: Comparative Observational Study

Background The recognition and interpretation of abnormal blood cell morphology is often the first step in diagnosing underlying serious systemic illness or leukemia. Supporting the staff who interpret blood film morphology is therefore essential for a safe laboratory service. This paper describes an open-access, web-based decision support tool, developed by the authors to support morphological diagnosis, arising from earlier studies identifying mechanisms of error in blood film reporting. The effectiveness of this intervention was assessed using the unique resource offered by the online digital morphology Continuing Professional Development scheme (DM scheme) offered by the UK National External Quality Assessment Service for Haematology, with more than 3000 registered users. This allowed the effectiveness of decision support to be tested within a defined user group, each of whom viewed and interpreted the morphology of identical digital blood films. Objective The primary objective of the study was to test the effectiveness of the decision support system in supporting users to identify and interpret abnormal morphological features. The secondary objective was to determine the pattern and frequency of use of the system for different case types, and to determine how users perceived the support in terms of their confidence in decision-making. Methods This was a comparative study of identical blood films evaluated either with or without decision support. Selected earlier cases from the DM scheme were rereleased as new cases but with decision support made available; this allowed a comparison of data sets for identical cases with or without decision support. To address the primary objectives, the study used quantitative evaluation and statistical comparisons of the identification and interpretation of morphological features between the two different case releases. To address the secondary objective, the use of decision support was assessed using web analytical tools, while a questionnaire was used to assess user perceptions of the system. Results Cases evaluated with the aid of decision support had significantly improved accuracy of identification for relevant morphological features (mean improvement 9.8%) and the interpretation of those features (mean improvement 11%). The improvement was particularly significant for cases with higher complexity or for rarer diagnoses. Analysis of website usage demonstrated a high frequency of access for web pages relevant to each case (mean 9298 for each case, range 2661-24,276). Users reported that the decision support website increased their confidence for feature identification (4.8/5) and interpretation (4.3/5), both within the context of training (4.6/5) and also in their wider laboratory practice (4.4/5). Conclusions The findings of this study demonstrate that directed online decision support for blood morphology evaluation improves accuracy and confidence in the context of educational evaluation of digital films, with effectiveness potentially extending to wider laboratory use. </jats:sec

EMQN best practice guidelines for molecular and haematology methods for carrier identification and prenatal diagnosis of the haemoglobinopathies

Haemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. Carrier identification and prenatal diagnosis represent valuable procedures that identify couples at risk for having affected children, so that they can be offered options to have healthy offspring. Molecular diagnosis facilitates prenatal diagnosis and definitive diagnosis of carriers and patients (especially ‘atypical’ cases who often have complex genotype interactions). However, the haemoglobin disorders are unique among all genetic diseases in that identification of carriers is preferable by haematological (biochemical) tests rather than DNA analysis. These Best Practice guidelines offer an overview of recommended strategies and methods for carrier identification and prenatal diagnosis of haemoglobinopathies, and emphasize the importance of appropriately applying and interpreting haematological tests in supporting the optimum application and evaluation of globin gene DNA analysis