Wing size and shape variation of Phlebotomus papatasi (Diptera: Psychodidae) populations from the south and north slopes of the Atlas Mountains in Morocco

The wing shape and size morphology of populations of the medically important phlebotomine sand fly, Phlebotomus papatasi, were examined in two endemic (south of the Atlas Mountains) and nonendemic (north of the Atlas Mountains) foci of cutaneous leishmaniasis by using geometric morphometrics in Morocco. Although it is present in all of Morocco, P. papatasi is the main vector of Leishmania major in only southern part of the Atlas Mountains. There are four major mountain ranges that serve as geographical barriers for species distribution in the study area and at least four gaps were recognized among these barriers. We found statistically significant differences in wing shape morphology between southern and northern populations. Analysis clearly recognized two main groups of populations on both sides of the mountains. The graphical depiction of Principal Component Analysis (PCA) and Canonical Variates Analysis (CVA) confirmed our morphometric study suggesting that the difference in wing morphology between the populations indicates that the population of P. papatasi shows phenotypic plasticity in the study area. According to centroid size analyses, which were used as measures of wing size differences among different sites, the north population of P. papatasi had relatively larger wings than the south population.     

Combining two teaching techniques for young children on Aedes aegypti control: effects on entomological indices in western Mexico

A study of the effect of educating four- to six-year-old children in mosquito control was recently conducted in a city in the state of Jalisco, western Mexico. Four neighborhood districts were selected. Children attending one kindergarten in each of two experimental districts were taught mosquito control with a video from the American Mosquito Control Association (AMCA), joined to the use of the AMCA Touch Table Technique. The entomological indices monitored in the study decreased significantly (P<0.05) in houses in the experimental districts, apparently because parents acted on the comments and suggestions of the children and eliminated or monitored containers used as oviposition sites by mosquitoes. Based on these results, combining both techniques for teaching children mosquito control is a potentially useful tool for control efforts in Mexico and other places in Latin America.     

Dermal application of nitric oxide releasing acidified nitrite-containing liniments significantly reduces blood pressure in humans

Vascular ischemic diseases, hypertension, and other systemic hemodynamic and vascular disorders may be the result of impaired bioavailability of nitric oxide (NO). NO but also its active derivates like nitrite or nitroso compounds are important effector and signal molecules with vasodilating properties. Our previous findings point to a therapeutical potential of cutaneous administration of NO in the treatment of systemic hemodynamic disorders. Unfortunately, no reliable data are available on the mechanisms, kinetics and biological responses of dermal application of nitric oxide in humans in vivo. The aim of the study was to close this gap and to explore the therapeutical potential of dermal nitric oxide application. We characterized with human skin in vitro and in vivo the capacity of NO, applied in a NO-releasing acidified form of nitrite-containing liniments, to penetrate the epidermis and to influence local as well as systemic hemodynamic parameters. We found that dermal application of NO led to a very rapid and significant transepidermal translocation of NO into the underlying tissue. Depending on the size of treated skin area, this translocation manifests itself through a significant systemic increase of the NO derivates nitrite and nitroso compounds, respectively. In parallel, this translocation was accompanied by an increased systemic vasodilatation and blood flow as well as reduced blood pressure. We here give evidence that in humans dermal application of NO has a therapeutic potential for systemic hemodynamic disorders that might arise from local or systemic insufficient availability of NO or its bio-active NO derivates, respectively.     

Not4 enhances JAK/STAT pathway-dependent gene expression in Drosophila and in human cells

The JAK/STAT pathway is essential for organogenesis, innate immunity, and stress responses in Drosophila melanogaster. The JAK/STAT pathway and its associated regulators have been highly conserved in evolution from flies to humans. We have used a genome-wide RNAi screen in Drosophila S2 cells to identify regulators of the JAK/STAT pathway, and here we report the characterization of Not4 as a positive regulator of the JAK/STAT pathway. Overexpression of Not4 enhanced Stat92E-mediated gene responses in vitro and in vivo in Drosophila. Specifically, Not4 increased Stat92E-mediated reporter gene activation in S2 cells; and in flies, Not4 overexpression resulted in an 8-fold increase in Turandot M (TotM) and in a 4-fold increase in Turandot A (TotA) stress gene activation when compared to wild-type flies. Drosophila Not4 is structurally related to human CNOT4, which was found to regulate interferon-γ- and interleukin-4-induced STAT-mediated gene responses in human HeLa cells. Not4 was found to coimmunoprecipitate with Stat92E but not to affect tyrosine phosphorylation of Stat92E in Drosophila cells. However, Not4 is required for binding of Stat92E to its DNA recognition sequence in the TotM gene promoter. In summary, Not4/CNOT4 is a novel positive regulator of the JAK/STAT pathway in Drosophila and in humans.     

Detection and monitoring of normal and leukemic cell populations with hierarchical clustering of flow cytometry data

Flow cytometry is a valuable tool in research and diagnostics including minimal residual disease (MRD) monitoring of hematologic malignancies. However, its gradual advancement toward increasing numbers of fluorescent parameters leads to information rich datasets, which are challenging to analyze by standard gating and do not reflect the multidimensionality of the data. We have developed a novel method to analyze complex flow cytometry data, based on hierarchical clustering analysis (HCA) but with a new underlying algorithm, using Mahalanobis distance measure. HCA is scalable to analyze complex multiparameter datasets (here demonstrated on up to 12 color flow cytometry and on a 20-parameter synthetic dataset). We have validated this method by comparison with standard gating approaches when performed independently by expert cytometrists. Acute lymphoblastic leukemia blast populations were analyzed in diagnostic and follow-up datasets (n = 123) from three centers. HCA results correlated very well (Passing-Bablok correlation coefficient = 0.992, slope = 1, intercept = -0.01) with standard gating data obtained by the I-BFM FLOW-MRD study group. To further improve the performance in follow-up samples with low MRD levels and to automate MRD detection, we combined HCA with support vector machine (SVM) learning. HCA in combination with SVM provides a novel diagnostic tool that not only allows analysis of increasingly complex flow cytometry data but also is less observer-dependent compared with classical gating and has potential for automation.     

Cell analysis in cerebrospinal fluid (CSF) using Sysmex? hematology analyzers XT-4000i and XE-5000: evaluation with CSF controls of the Joint German Society for Clinical Chemistry and Laboratory Medicine (DGKL)

In cerebrospinal fluid (CSF) analysis, hematology analyzers (HAs) Sysmex? XT-4000i and XE-5000, equipped with flow cytometry (FCM), were used to count cells and differentiate leukocytes into mononuclear and polymorphonuclear cells (MNCs, PMCs) applying body fluid mode. FCM was evaluated with 20 DGKL CSF controls containing viable human leukocytes and erythrocytes. HA values were compared with reference values by Passing/Bablok regression analysis to reveal conformity. Conformity of white blood cells (WBCs) was obtained with native leukocytes, counted in calibrated Fuchs-Rosenthal chamber as reference; red blood cell counts proved inaccurate. CV <40% with WBC counts <20 per μL impairs accuracy. Reference WBC differentiation was assayed using FACS Canto II? and FC-500 SN with anti-CD45, anti-CD14, anti-CD16, anti-CD16/56 [Becton Dickinson (BD); Beckman Coulter (BC)]. BD FACS lysing solution?-no-wash-procedure was applied. BC pretreatment with Versalyse lysing solution was not recommended. MNCs (lymphocytes + monocytes) were significantly lower (～14%) on both HAs; PMCs (granulocytes or sum of neutrophils + eosinophils + basophils: range 1-86 M/L) were significantly higher (～2.2-fold). WBC HA differentiation is not reliable because MNC/PMC differentiation yielded lower and higher values than FACS-FCM references, respectively. This is attributed to incorrect discrimination of leukocytes with rounded/nonrounded nuclei; adding leukocytes with nonrounded nuclei to too low HA MNCs (about 40% not-activated) yielded P/B conformity; subtraction of leukocytes with nonrounded nuclei from elevated HA PMCs showed conformity (about 85% activated). Nucleus/activation state of leukocytes was assessed using microhistology. Sysmex XT-4000i and XE-5000 HAs systems are inappropriate for complete CSF cell analysis.     

Obesity and postprandial lipemia in adolescents: risk factors for cardiovascular disease

In the last 50 years, obesity has become a global epidemic and is one of the main public health problems in many parts of the world. Adolescence is a critical period regarding weight control. The factors determining obesity include a complex group of interrelated biological, behavioral and environmental factors which reinforce each other. In children and adolescents, obesity is associated with premature cardiovascular diseases, diabetes mellitus type 2, acanthosis nigricans, respiratory and skeletal muscle problems, as well as psychological problems. The clinical manifestations of cardiovascular disease begin in middle age. Nevertheless, studies indicate that the atherosclerotic process begins to develop during childhood. Postprandial hyperlipemia is a physiological process that occurs several times a day after the complete absorption of a diet including lipids and has been suggested as a risk factor for coronary heart disease (CHD). New study areas include the effects of different fatty acids, lipid sources (endogenous and exogenous), and the effect ingesting alcoholic beverages during meals. Given the evidence that postprandial lipidemia is an independent risk factor for CHD, it is vital to establish normative values for children and adolescents such that more effective and efficient preventive and therapeutic measures can be adopted.     

异源表达NADH选择性氧化酶提高光滑球拟酵母酵解速率及丙酮酸生产强度

摘要：【目的】为进一步提高光滑球拟酵母(Torulopsis glabrata)葡萄糖代谢速率及丙酮酸生产强度。【方法】将源于荚膜胞浆菌(Histoplasma capsulatum)的编码选择性氧化酶的AOX1基因过量表达于T. glabrata中,获得了一株线粒体内NADH氧化途径发生改变且胞内总NADH 氧化酶活性提高1.8倍的重组菌株AOX。【结果】与出发菌株CON比较,细胞浓度以及发酵周期降低了20.3%和10.7%,而平均比葡萄糖消耗速率和丙酮酸合成速率分别提高了34.7%和54.1%。其原因