Fish oil supplementation alters numbers of circulating endothelial progenitor cells and micro particles independent of eNOS genotype

Background Emerging cellular markers of endothelial damage and repair include endothelial microparticles (EMPs) and endothelial progenitor cells (EPCs) respectively. Effects of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) and influence of genetic background on these markers are not known. Objective This study investigated the effects of fish oil supplementation on both classical and novel markers of endothelial function in subjects prospectively genotyped for the Asp298 eNOS polymorphism and at moderate risk of CVD. Design 84 subjects with moderate risk of CVD (n=40 GG and n=44 GT/TT) completed a randomized, double-blind, placebo-controlled, 8-week cross-over trial of fish oil supplementation providing 1.5 g/d LC n-3 PUFA. Effects of genotype and fish oil supplementation on the blood lipid profile, inflammatory markers, vascular function (EndoPAT) and numbers of circulating EPCs and EMP (flow cytometry) were assessed. Results There was no significant effect of fish oil supplementation on blood pressure, plasma lipids or plasma glucose, although there was a trend (P = 0.069) towards a decrease in plasma TG concentration after FO supplementation compared to placebo. GT/TT subjects tended to have higher levels of total cholesterol and LDL-cholesterol, but vascular function was not affected by either treatment or eNOS genotype. Biochemical markers of endothelial function were also unaffected by treatment and eNOS genotype. In contrast, there was a significant effect of fish oil supplementation on cellular markers of endothelial function. Fish oil supplementation increased numbers of EPCs and reduced numbers of EMPs relative to the placebo, potentially favouring maintenance of endothelial integrity. There was no influence of genotype for any of the cellular markers of endothelial function, indicating that the effects of fish oil supplementation were independent of eNOS genotype. Conclusions Emerging cellular markers of endothelial damage, integrity and repair appear to be sensitive to potentially beneficial modification by dietary n-3 PUFA.

Impact of chronic neonicotinoid exposure on honeybee colony performance and queen supersedure

BACKGROUND: Honeybees provide economically and ecologically vital pollination services to crops and wild plants. During the last decade elevated colony losses have been documented in Europe and North America. Despite growing consensus on the involvement of multiple causal factors, the underlying interactions impacting on honeybee health and colony failure are not fully resolved. Parasites and pathogens are among the main candidates, but sublethal exposure to widespread agricultural pesticides may also affect bees. METHODOLOGY/PRINCIPAL FINDINGS: To investigate effects of sublethal dietary neonicotinoid exposure on honeybee colony performance, a fully crossed experimental design was implemented using 24 colonies, including sister-queens from two different strains, and experimental in-hive pollen feeding with or without environmentally relevant concentrations of thiamethoxam and clothianidin. Honeybee colonies chronically exposed to both neonicotinoids over two brood cycles exhibited decreased performance in the short-term resulting in declining numbers of adult bees (-28%) and brood (-13%), as well as a reduction in honey production (-29%) and pollen collections (-19%), but colonies recovered in the medium-term and overwintered successfully. However, significantly decelerated growth of neonicotinoid-exposed colonies during the following spring was associated with queen failure, revealing previously undocumented long-term impacts of neonicotinoids: queen supersedure was observed for 60% of the neonicotinoid-exposed colonies within a one year period, but not for control colonies. Linked to this, neonicotinoid exposure was significantly associated with a reduced propensity to swarm during the next spring. Both short-term and long-term effects of neonicotinoids on colony performance were significantly influenced by the honeybees' genetic background. CONCLUSIONS/SIGNIFICANCE: Sublethal neonicotinoid exposure did not provoke increased winter losses. Yet, significant detrimental short and long-term impacts on colony performance and queen fate suggest that neonicotinoids may contribute to colony weakening in a complex manner. Further, we highlight the importance of the genetic basis of neonicotinoid susceptibility in honeybees which can vary substantially.

A tillering inhibition gene influences root-shoot carbon partitioning and pattern of water use to improve wheat productivity in rainfed environments

Genetic modification of shoot and root morphology has potential to improve water and nutrient 19 uptake of wheat crops in rainfed environments. Near-isogenic lines (NILs) varying for a tillering 20 inhibition (tin) gene and representing multiple genetic backgrounds were investigated in contrasting 21 controlled environments for shoot and root growth. Leaf area, shoot and root biomass were similar 22 until tillering whereupon reduced tillering in tin-containing NILs produced reductions of up to 60% in 23 total leaf area and biomass, and increases in total root length of up to 120% and root biomass to 24 145%. Together, root-to-shoot ratio increased two-fold with the tin gene. The influence of tin on shoot 25 and root growth was greatest in the cv. Banks genetic background, particularly in the biculm-selected 26 NIL, and was typically strongest in cooler environments. A separate de-tillering study confirmed 27 greater root-to-shoot ratios with regular tiller removal in non-tin containing genotypes. In validating 28 these observations in a rainfed field study, the tin allele had a negligible effect on seedling growth but 29 was associated with significantly (P<0.05) reduced tiller number (-37%), leaf area index (-26%) and 30 spike number (-35%) to reduce plant biomass (-19%) at anthesis. Root biomass, root-to-shoot ratio at 31 early stem elongation and root depth at maturity were increased in tin-containing NILs. Soil water use 32 was slowed in tin-containing NILs resulting in greater water availability, greater stomatal 33 conductance, cooler canopy temperatures and maintenance of green leaf area during grain-filling. 34 Together these effects contributed to increases in harvest index and grain yield. In both the controlled 35 and field environments, the tin gene was commonly associated with increased root length and biomass 36 but the significant influence of genetic background and environment suggests careful assessment of 37 tin-containing progeny in selection for genotypic increases in root growth.

Transcriptional regulation differs in affected facioscapulohumeral muscular dystrophy patients compared to asymptomatic related carriers

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disorder that has been associated with a contraction of 3.3-kb repeats on chromosome 4q35. FSHD is characterized by a wide clinical inter- and intrafamilial variability, ranging from wheelchair-bound patients to asymptomatic carriers. Our study is unique in comparing the gene expression profiles from related affected, asymptomatic carrier, and control individuals. Our results suggest that the expression of genes on chromosome 4q is altered in affected and asymptomatic individuals. Remarkably, the changes seen in asymptomatic samples are largely in products of genes encoding several chemokines, whereas the changes seen in affected samples are largely in genes governing the synthesis of GPI-linked proteins and histone acetylation. Besides this, the affected patient and related asymptomatic carrier share the 4qA161 haplotype. Thus, these polymorphisms by themselves do not explain the pathogenicity of the contracted allele. Interestingly, our results also suggest that the miRNAs might mediate the regulatory network in FSHD. Together, our results support the previous evidence that FSHD may be caused by transcriptional dysregulation of multiple genes, in cis and in trans, and suggest some factors potentially important for FSHD pathogenesis. The study of the gene expression profiles from asymptomatic carriers and related affected patients is a unique approach to try to enhance our understanding of the missing link between the contraction in D4Z4 repeats and muscle disease, while minimizing the effects of differences resulting from genetic background.

Clinical presentation of tuberculoid leprosy in an epidermodysplasia verruciformis patient

Epidermodysplasia verruciformis (EV) is triggered by a variety of mechanisms that at least partly include genetic background. We present a Brazilian man with a 30-year history of flat, wart-like lesions with clinical, histopathological, and evolutive aspects consistent with papillomavirus (HPV)-associated EV. Histological analysis of the wart lesions showed epidermis with hyperkeratosis, regular acanthosis, hypergranulosis, and cells with abundant basophilic cytoplasm. Moreover, a perivascular lymphocytic infiltrate was found in the superficial dermis, consistent with a viral wart. Type-2-HPV DNA was detected in various fragments of skin-wart lesions using the polymerase chain reaction (PCR). Two years after the EV diagnosis, the patient presented with an anesthetic well-demarcated, erythematous and mildly scaly plaque on his right forearm. A histopathological analysis of this lesion demonstrated the presence of a compact tuberculoid granuloma. Ziehl-Neelsen staining demonstrated the presence of rare acid-fast bacilli and confirmed the tuberculoid leprosy diagnosis. The patient's Mitsuda Intradermal Reaction was positive. To elucidate the possible mechanism involved in this case of EV, we genotyped the HLA genes of this patient. DQB genotyping showed the polymorphic HLA alleles DQB1*0301 and 0501. The patient was treated with a paucibacillary multidrug therapy scheme, and the disease was cured in six months. This report describes an EV patient with an M. leprae infection, confirming that tuberculoid leprosy patients possess a relatively specific and efficient cell-mediated immunity against the bacillus and, therefore, localized forms of the disease. Moreover, we show the possible involvement of the polymorphic HLA alleles DQB1*0301 and 0501 in EV induction mechanisms.

Bovine gene polymorphisms related to fat deposition and meat tenderness

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Altered patterns of maltose and glucose fermentation by brewing and wine yeasts influenced by the complexity of nitrogen source

Maltose and glucose fermentations by industrial brewing and wine yeasts strains were strongly affected by the structural complexity of the nitrogen source. In this study, four Saccharomyces cerevisiae strains, two brewing and two wine yeasts, were grown in a medium containing maltose or glucose supplemented with a nitrogen source varying from a single ammonium salt (ammonium sulfate) to free amino acids (casamino acids) and peptides (peptone). Diauxie was observed at low sugar concentration for brewing and wine strains, independent of nitrogen supplementation, and the type of sugar. At high sugar concentrations altered patterns of sugar fermentation were observed, and biomass accumulation and ethanol production depended on the nature of the nitrogen source and were different for brewing and wine strains. In maltose, high biomass production was observed under peptone and casamino acids for the brewing and wine strains, however efficient maltose utilization and high ethanol production was only observed in the presence of casamino acids for one brewing and one wine strain studied. Conversely, peptone and casamino acids induced higher biomass and ethanol production for the two other brewing and wine strains studied. With glucose, in general, peptone induced higher fermentation performance for all strains, and one brewing and wine strain produced the same amount of ethanol with peptone and casamino acids supplementation. Ammonium salts always induced poor yeast performance. The results described in this paper suggest that the complex nitrogen composition of the cultivation medium may create conditions resembling those responsible for inducing sluggish/stuck fermentation, and indicate that the kind and concentration of sugar, the complexity of nitrogen source and the yeast genetic background influence optimal industrial yeast fermentation performance.

Serum titres of anti-glutamic acid decarboxylase-65 and anti-IA-2 autoantibodies are associated with different immunoregulatory milieu in newly diagnosed type 1 diabetes patients

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Prevalence of rhinitis among Brazilian schoolchildren: ISAAC phase 3 results

Objective: The International Study of Asthma and Allergies in Childhood (ISAAC) is a standardized method that allows international and regional comparisons of asthma and allergic diseases prevalence. The objective of this study was to evaluate the prevalence of rhinitis and related symptoms among 6-7 year-old children (SC) and 13-14 year-old adolescents (AD) from 20 Brazilian cities applying the ISAA C's standardized written questionnaire (WQ). Methods: ISAAC's WQ was applied to 23,422 SC and 58,144 AD living in different regions of Brazil: North (N), Northeast (NE), Middle West (MW), Southeast (SE), and South (S). Results: The prevalence of rhinoconjunctivitis in the last year ranged from 10.3% to 17.4% and from 8.9% to 28.5% among SC and AD, respectively. Considering SC the highest values were observed in SE region. In NE, the prevalence in countryside centres was higher than those along the coast. Among AD, the highest values were observed in N and S regions, mainly in Pará (Belém). The evaluation of populations probably with the same genetic background has shown higher prevalence among those living in urban centres (capital) in comparison to those in the countryside. Conclusions: The prevalence of rhinitis and related symptoms were variable and predominate in Brazilian N and NE centres.

Historical and recent biological markers of exposure to fluoride

Recent and historical biomarkers assess chronic or subchronic exposure to fluoride. The most studied recent biomarkers are nails and hair. Both can be non-invasively obtained, although collection of nails is more accepted by the subjects. External contamination may be a problem for both biomarkers and still needs to be better evaluated. Nails have been more extensively studied. Although the available knowledge does not allow their use as predictors of dental fluorosis by individual subjects, since reference values of fluoride have not yet been established, they have a strong potential for use in epidemiological surveys. Toenails should be preferred instead of fingernails, and variables that are known to affect nail fluoride concentrations - such as age, gender and geographical area - should be considered. The main historical biomarkers that could indicate total fluoride body burden are bone and dentin. Of these, bone is more studied, but its fluoride concentrations vary according to the type of bone and subjects' age and gender. They are also influenced by genetic background, renal function and remodeling rate, variables that complicate the establishment of a normal range of fluoride levels in bone that could indicate 'desirable' exposure to fluoride. The main issue when attempting to use bone as biomarker of fluoride exposure is the difficulty and invasiveness of sample collection. In this aspect, collection of dentin, especially from 3rd molars that are commonly extracted, is advantageous. However, mean values also span a wide range and reference concentrations have not been published yet. © 2011 S. Karger AG, Basel.

Participação do gene Alc11a1 na infecção por Paracoccidioides brasiliensis em linhagens de camundongos selecionados segundo a alta ou baixa reatividade inflamatória aguda

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Genomic divergence of zebu and taurine cattle identified through high-density SNP genotyping

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Periodontopathogens levels and clinical response to periodontal therapy in individuals with the interleukin-4 haplotype associated with susceptibility to chronic periodontitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The effect of conventional mechanical periodontal treatment on red complex microorganisms and clinical parameters in Down syndrome periodontitis patients: a pilot study

Periodontal disease (PD) is induced by a complex microbiota, such as Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola (together called the red complex), which triggers intense inflammatory reaction. Down syndrome (DS) individuals demonstrate a high prevalence of PD compared with those who are otherwise chromosomally normal (euploids). This pilot study aimed to evaluate the effect of non-surgical periodontal treatment in DS chronic periodontitis patients on clinical and microbiological parameters. Patients with chronic periodontitis, 23 DS and 12 euploids (control group), were submitted to non-surgical mechanical periodontal treatment, followed by maintenance for 45 days. Clinical parameters after periodontal treatment were similar in diseased and healthy sites, independent of the genetic background. Diseased sites of DS and control patients harbored similar levels of P. gingivalis and T. forsythia at baseline, but significantly higher levels of T. denticola were found in DS patients. Increased levels of P. gingivalis at healthy sites were found in DS individuals. Non-surgical periodontal therapy decreased the levels of red complex microorganisms and improved the tested clinical parameters of diseased sites in both groups. However, the levels of red complex bacteria were higher in diseased sites of DS patients after the periodontal treatment. We conclude in this pilot study that, although the mechanical periodontal treatment seemed to be effective in DS subjects over a short-term period, the red complex bacteria levels did not decrease significantly in diseased sites, as occurred in controls. Therefore, for DS patients, it seems that the conventional non-surgical periodontal therapy should be improved by utilizing adjuvants to reduce the presence of periodontopathogens.

The role of HLA-G molecule and HLA-G gene polymorphisms in tumors, viral hepatitis, and parasitic diseases

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)