A Model of Insulin Resistance in Mice, Born to Diabetic Pregnancy, Is Associated with Alterations of Transcription-Related Genes in Pancreas and Epididymal Adipose Tissue

Objective. This study is conducted on a model of insulin-resistant (IR) mice born to dams which were rendered diabetic by the administration of streptozotocin. Methods. Adult IR and control offspring were selected and we determined the mRNA expression of transcription factors known to modulate pancreatic and adipose tissue activities and inflammation. Results. We observed that serum insulin increased, and the mRNA of insulin gene transcription factors, Pdx-1, Nkx6.1 and Maf-A, were upregulated in IR mice pancreas. Besides, their pancreatic functional capacity seemed to be exhausted as evidenced by low expression of pancreatic Glut2 and glucokinase mRNA. Though IR offspring exhibited reduced epididymal adipose tissue, their adipocytes seemed to be differentiated into macrophage-like cells, as they exhibited upregulated CD14 and CD68 antigens, generally expressed by macrophages. However, there was no peripheral macrophages infiltration into epididymal adipose tissue, as the expression of F4/80, a true macrophage marker, was undetectable. Furthermore, the expression of IL-6, TNF-α and TLR-2, key players of insulin resistance, was upregulated in the adipose tissue of IR offspring. Conclusion. Insulin resistant state in mice, born to diabetic pregnancy, alters the expression of function-related genes in pancreas and epididymal adipose tissue and these offspring are prone to develop metabolic syndrome

Multiple insecticide resistance in an infected population of the malaria vector Anopheles funestus in Benin.

BACKGROUND Knowledge on the spread and distribution of insecticide resistance in major malaria vectors such as Anopheles funestus is key to implement successful resistance management strategies across Africa. Here, by assessing the susceptibility status of an inland population of An. funestus Giles (Kpome) and investigating molecular basis of resistance, we show that multiple resistance and consistent plasmodium infection rate are present in Anopheles funestus populations from Kpome. METHODS The insecticide susceptibility level of collected Anopheles funestus was assessed. Synergist (PBO) was used to screen resistance mechanisms. The TaqMan technique was used for genotyping of insecticide resistant alleles and detecting plasmodium infection levels. The nested PCR was used to further assess the plasmodium infection rate. RESULTS The TaqMan analysis of plasmodial infections revealed an infection rate (18.2 %) of An. funestus in this locality. The WHO bioassays revealed a multiple phenotypic resistance profile for An. funestus in Kpome. This population is highly resistant to pyrethroids (permethrin and deltamethrin), organochlorines (DDT), and carbamates (bendiocarb). A reduced susceptibility was observed with dieldrin. Mortalities did not vary after pre-exposure to PBO for DDT indicating that cytochrome P450s play little role in DDT resistance in Kpome. In contrast, we noticed, a significant increase in mortalities when PBO was combined to permethrin suggesting the direct involvement of P450s in pyrethroid resistance. A high frequency of the L119F-GSTe2 DDT resistance marker was observed in the wild DDT resistant population (9 %RS and 91 %RR) whereas the A296S mutation was detected at a low frequency (1 %RS and 99 %SS). CONCLUSION The presence of multiple resistance in An. funestus populations in the inland locality of Kpome is established in this study as recently documented in the costal locality of Pahou. Data from both localities suggest that resistance could be widespread in Benin and this highlights the need for further studies to assess the geographical distribution of insecticide resistance across Benin and neighboring countries as well as a more comprehensive analysis of the resistance mechanisms involved

Acquisition of natural humoral immunity to <i>P. falciparum</i> in early life in Benin:impact of clinical, environmental and host factors

To our knowledge, effects of age, placental malaria infection, infections during follow-up, nutritional habits, sickle-cell trait and individual exposure to Anopheles bites were never explored together in a study focusing on the acquisition of malaria antibody responses among infants living in endemic areas. Five hundred and sixty-seven Beninese infants were weekly followed-up from birth to 18 months of age. Immunoglobulin G (IgG), IgG1 and IgG3 specific for 5 malaria antigens were measured every 3 months. A linear mixed model was used to analyze the effect of each variable on the acquisition of antimalarial antibodies in 6- to 18-month old infants in univariate and multivariate analyses. Placental malaria, nutrition intakes and sickle-cell trait did not influence the infant antibody levels to P. falciparum antigens. In contrary, age, malaria antibody levels at birth, previous and present malaria infections as well as exposure to Anopheles bites were significantly associated with the natural acquisition of malaria antibodies in 6- to 18-month old Beninese infants. This study highlighted inescapable factors to consider simultaneously in an immuno-epidemiological study or a vaccine trial in early life

Modulation of immune cells and Th1/Th2 cytokines in insulin-treated type 2 diabetes mellitus.

Background: The role of the immune system in insulin resistance associated with type 2 diabetes has been suggested. Objectives: We assessed the profile of Th1/Th2 cytokines along with the frequencies of immune cells in insulin-treated type 2 diabetic patients (T2DP). Methods: 45 T2D patients and 43 age-matched healthy subjects were selected. Serum concentrations of T-helper type 1 (Th1) and Th2 cytokines and the frequencies of innate and adaptive immunity cells were assessed. Results: T2DP were hyperglycemic and showed high level of insulin, normal levels of triglycerides and total-cholesterol and without any change in HDL-cholesterol.Compared to healthy subjects, T2DP exhibited significant decreased frequencies of neutrophils, without any change in monocytes, eosinophils and natural killer cells. The percentages of total lymphocytes (CD3+) and CD8+-T-cells decreased whereas those of regulatory T-cells increased without any change in CD4+ T-cells in T2DP. Interestingly, the frequencies of effector CD4+-T and B-cells increased in T2DP. Serum concentrations of IL-2, IFN-\u3b3 and IL-4 decreased while IL-10 significantly enhanced in T2DP, suggesting a differentiation of CD4+T helper cells towards IL-10-producing- Teff-cells in these patients. Conclusion: Insulin-treated type 2 diabetes is associated with anti-inflammatory profile consistent with differentiation of CD4+-Th-cells towards IL-10-producing-Teff-cells, concomitant with increased frequencies of Treg and B-cells, and this may probably offer prevention against certain infections or autoimmune/inflammatory diseases

Infections with Plasmodium falciparum during pregnancy affect VAR2CSA DBL-5 domain-specific T cell cytokine responses

Background: Current knowledge of human immunological responses to pregnancy-associated malaria-specific Plasmodium falciparum protein VAR2CSA concerns almost exclusively B cell-driven antibody-mediated activity. Knowledge of VAR2CSA-specific T cell-mediated activity is minimal by comparison, with only a single published report of a study investigating VAR2CSA-derived peptide-specific T cell responses. The study described here represents an attempt to redress this balance. Methods: Within the framework of a cohort study of 1037 pregnant Beninese, sub-groups were selected on the basis of the documented presence/absence of infection with P. falciparum and conducted detailed immunological assessments both at inclusion into the study and at delivery. Peripheral blood mononuclear cells were isolated, stimulated in vitro, and VAR2CSA DBL-5 domain-specific, IFN-gamma-secreting T-cell frequencies and cytokine responses were quantified using flow cytometric techniques. Multivariate analyses were used to determine primarily whether the T cell-mediated DBL5-specific activity measured was associated with infection by P. falciparum adjusted for gravidity, anaemia and other cofactors. Results: Infections with P. falciparum detected at inclusion were associated with enhanced non-specific TNF responses, whilst diminished non-specific and DBL-5-specific IL-10 responses were associated with infections detected at delivery. Infections during pregnancy led to enhanced non-specific and DBL-5-specific IFN-gamma responses detectable at delivery but to concomitantly lower DBL-5-specific CD8+ IFN-gamma responses. Prospective assessments indicated that non-specific pro-inflammatory responses detectable at inclusion in the study were associated with the occurrence of infections subsequently during pregnancy. Conclusions: The findings represent a first step in elucidating the quantity and quality of cellular immunological responses to VAR2CSA, which will help in the development of the primary vaccine candidate for prevention of pregnancy-associated malaria

Findings of the Survey on Prevention of Plagiarism in Lithuanian Research Journals

AbstractAt the end of 2011, the Association of Lithuanian Serials initiated a survey, which aimed to ascertain whether Lithuanian journal editors, reviewers and authors encountered plagiarism, self-plagiarism and how they understood originality of a paper. Additionally, the survey looked at methods used for plagiarism prevention by editors and reviewers as well as ways, in which editors managed issues related to plagiarism. The survey suggests that no unanimous decision exists regarding the originality of a manuscript and that editors expect reviewers to identify plagiarism with little use of technologies. While answering to survey questions, respondents provided numerous comments. This demonstrates that plagiarism is a burning issue and scientific misconduct policy is needed in Lithuania. The survey was conducted during the period when the Lithuanian Research Council initiated the procedure for establishing the Ombudsman position. The Lithuanian Research Council funded several projects in 2012 and 2013, the aim of which was to familiarise the Lithuanian academic community with plagiarism prevention technologies and ethical aspects in academic publishing. The projects administrated by the Association of Lithuanian Serials provide research journal publishers and researchers related to journal publishing with a possibility of using CrossCheck system and discussing editorial policies

Evolution of the levels of human leukocyte antigen G (HLA-G) in Beninese infant during the first year of life in a malaria endemic area: using latent class analysis

Abstract Background: HLA-G, a non-classical HLA class I antigen, is of crucial interest during pregnancy by inhibiting maternal immune response. Its role during infections is discussed, and it has been described that high levels of soluble HLA-G during childhood increase the risk of malaria. To explore more precisely interactions between soluble HLA-G and malaria, latent class analysis was used to test whether distinct sub-populations of children, each with distinctive soluble HLA-G evolutions may suggest the existence of groups presenting variable malaria susceptibility. Method: A study was conducted in Benin from 2010 to 2013 and 165 children were followed from birth to 12 months. Evolution of soluble HLA-G was studied by the latent class method. Results: Three groups of children were identified: one with consistently low levels of soluble HLA-G during follow-up, a second with very high levels and a last intermediate group. In all groups, low birth weight, high number of malaria infections and high exposure to malaria transmission were associated with high level of soluble HLA-G. Placental malaria was not. Presence of soluble HLA-G in cord blood increased the probability of belonging to the highest trajectory. Conclusion: These results, together with previous ones, confirm the important role of HLA-G in the individual susceptibility to malaria. Assaying soluble HLA-G at birth could be a good indicator of newborns more fragile and at risk of infections during childhood

Семантичні зміни в лексичному складі російської та української мов

Использование вычислительной техники и радиоэлектроники способствовало формированию специальной группы лексических единиц. Номинация новых явлений и понятий является актуальной проблемой нынешнего этапа развития языка. Изменение семантического наполнения – это один из способов решения данной проблемы. Расширение или сужение семантического объема слов способствует обогащению лексической системы, а именно терминологии.Використання обчислювальної техніки та радіоелектроніки спричинило формування спеціальної групи лексичних одиниць. Номінація нових явищ та понять є актуальною проблемою теперішнього етапу розвитку мови. Зміна семантичного об'єму – це один із засобів вирішення даної проблеми. Звуження або розширення семантичного наповнення сприяє збагаченню лексичної системи, а саме термінології.Using of radio-electronic devices forced the formation of a special group of lexical units. The nomination of new processes and notions is an actual problem of today's language development. Semantic changes of existing units is one of the decisions of the problem. Widening and narrowing of semantic meanings promotes the enrichment of lexical system, especially the system of terminology

Maternal Diabetes in Pregnancy: Early and Long-Term Outcomes on the Offspring and the Concept of “Metabolic Memory”

The adverse outcomes on the offspring from maternal diabetes in pregnancy are substantially documented. In this paper, we report main knowledge on impacts of maternal diabetes on early and long-term health of the offspring, with specific comments on maternal obesity. The main adverse outcome on progenies from pregnancy complicated with maternal diabetes appears to be macrosomia, as it is commonly known that intrauterine exposure to hyperglycemia increases the risk and programs the offspring to develop diabetes and/or obesity at adulthood. This “fetal programming”, due to intrauterine diabetic milieu, is termed as “metabolic memory”. In gestational diabetes as well as in macrosomia, the complications include metabolic abnormalities, degraded antioxidant status, disrupted immune system and potential metabolic syndrome in adult offspring. Furthermore, there is evidence that maternal obesity may also increase the risk of obesity and diabetes in offspring. However, women with GDM possibly exhibit greater macrosomia than obese women. Obesity and diabetes in pregnancy have independent and additive effects on obstetric complications, and both require proper management. Management of gestational diabetes mellitus and maternal obesity is essential for maternal and offspring's good health. Increasing physical activity, preventing gestational weight gain, and having some qualitative nutritional habits may be beneficial during both the pregnancy and offspring's future life