TREM-1 links dyslipidemia to inflammation and lipid deposition in atherosclerosis.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune responses, but its significance in non-infectious diseases remains unclear. Here, we demonstrate that TREM-1 promotes cardiovascular disease by exacerbating atherosclerosis. TREM-1 is expressed in advanced human atheromas and is highly upregulated under dyslipidemic conditions on circulating and on lesion-infiltrating myeloid cells in the Apoe(-/-) mouse model. TREM-1 strongly contributes to high-fat, high-cholesterol diet (HFCD)-induced monocytosis and synergizes with HFCD serum-derived factors to promote pro-inflammatory cytokine responses and foam cell formation of human monocyte/macrophages. Trem1(-/-)Apoe(-/-) mice exhibit substantially attenuated diet-induced atherogenesis. In particular, our results identify skewed monocyte differentiation and enhanced lipid accumulation as novel mechanisms through which TREM-1 can promote atherosclerosis. Collectively, our findings illustrate that dyslipidemia induces TREM-1 surface expression on myeloid cells and subsequently synergizes with TREM-1 to enhance monopoiesis, pro-atherogenic cytokine production and foam cell formation

Identification and molecular characterization of allergenic nsLTP from durum wheat (Triticum turgidum)

Background: Common wheat (Triticum aestivum) and durum wheat (T. turgidum) are both involved in Baker's asthma (BA) and food allergy (FA) including wheat-dependent exercise-induced asthma (WDEIA). However, allergens in durum wheat have not been described, and the over-expression of T. turgidum non-specific lipid-transfer protein (nsLTPs) is considered to increase resistance to phytopathogens. Objective: To identify and assess the allergenicity of nsLTP from T. turgidum. Methods: Recombinant T. turgidum nsLTP Tri tu 14 was generated and tested for structural integrity (circular dichroism-spectroscopy) and purity (SDS-PAGE). Thirty-two wheat allergic patients were enrolled: 20 Spanish patients (BA) with positive bronchial challenge to wheat flour, and 12 Italian patients (wheat FA/WDEIA) with positive double-blind placebo-controlled food challenge/open food challenge (OFC) to pasta. IgE values to wheat, Tri tu 14, Tri a 14 (T. aestivum) and Pru p 3 (P. persica) were determined by ImmunoCAP testing. Allergenic potency (in vitro mediator release) and IgE cross-reactivity were investigated. Results: Tri tu 14 was found to share 49% and 52% amino acid identity with Tri a 14 and Pru p 3, respectively. Among 25 Tri a 14 CAP positive sera, 23 (92%) were reactive to wheat extract, 22 (88%) to Tri tu 14 and 20 (80%) to Pru p 3. The correlation between Tri a 14 and Tri tu 14 specific IgE levels was r = 0.97 (BA) and r = 0.93 (FA/WDEIA), respectively. FA/WDEIA patients showed higher specific IgE values to Tri tu 14 and Pru p 3 than BA patients. Tri tu 14 displayed allergenic activity by mediator release from effector cells and IgE cross-reactivity with Pru p 3. The degree of IgE cross-reactivity between the two wheat nsLTPs varied between individual patients. Conclusions and Clinical Relevance: Sensitization to Tri tu 14 likely appears to be more important in wheat FA/WDEIA than in BA. Over-expression of Tri tu 14 in wheat would represent a risk for patients with nsLTP-mediated FA

Quantitative Analysis of Immunoglobulin E Reactivity Profiles in Patients Allergic or Sensitized to Natural Rubber Latex (Hevea Brasiliensis)

Characterized native and recombinant Hevea brasiliensis (rHev b) natural rubber latex (NRL) allergens are available to assess patient allergen sensitization profiles. OBJECTIVE: Quantification of individual IgE responses to the spectrum of documented NRL allergens and evaluation of cross-reactive carbohydrate determinants (CCDs) for more definitive diagnosis. METHODS: Sera of 104 healthcare workers (HCW; 51 German, 21 Portuguese, 32 American), 31 spina bifida patients (SB; 11 German, 20 Portuguese) and 10 Portuguese with multiple surgeries (MS) were analysed for allergen-specific IgE antibody (sIgE) to NRL, single Hev b allergens and CCDs with ImmunoCAP technology. RESULTS: In all patient groups rHev b 5-sIgE concentrations were the most pronounced. Hev b 2, 5, 6.01 and 13 were identified as the major allergens in HCW and combined with Hev b 1 and Hev b 3 in SB. In MS Hev b 1 displayed an intermediate relevance. Different sIgE antibody levels to native Hevea brasiliensis (nHev b) 2 and rHev b 6.01 allowed discrimination of SB with clinical relevant latex allergy vs. those with latex sensitization. Sensitization profiles of German, Portuguese and American patients were equivalent. rHev b 5, 6.01 and nHev b 13 combined detected 100% of the latex-allergic HCW and 80.1% of the SB. Only 8.3% of the sera showed sIgE response to CCDs. CONCLUSIONS: Hev b 1, 2, 5, 6.01 and 13 were identified as the major Hev b allergens and they should be present in standardized latex extracts and in vitro allergosorbents. CCDs are only of minor relevance in patients with clinical relevant latex allergy. Component-resolved diagnostic analyses for latex allergy set the stage for an allergen-directed immunotherapy strateg

[oral Health Among Preschool Children In Brazil, 1999].

To assess dental decay, gum diseases and fluorosis prevalence and evaluate treatment needs of public preschool children. A cross-sectional epidemiological survey on oral health was conducted in 2,805 public preschool children aged 5 and 6 years in Piracicaba, Brazil. Children were examined by a team of ten trained dentists. It was applied a consensus technique and intra and inter agreement among examiners was assessed using the percentage of agreement. Of the total, 44.3% children were free of dental decay at the age of 5 and 38.5% at the age of 6. The deciduous decay teeth index (dmf-t) was 2.64 at the age of 5 and 3.07 at the age of 6, and 31.9% and 37.9%, respectively, presented dmf-t greater than 3. The largest percent of treatment need (45.3%) was surface restoration. Regarding gum health, 68.6% and 72.6% of children aged 5 and 6 years presented gum bleeding. The prevalence of fluorosis was 2.6% at the age of 5 and 6.1% at the age of 6. It is necessary to develop appropriate actions and strategies for higher risk groups.37247-5

Saúde bucal dos pré-escolares, Piracicaba, Brasil, 1999

OBJECTIVE: To assess dental decay, gum diseases and fluorosis prevalence and evaluate treatment needs of public preschool children. METHODS: A cross-sectional epidemiological survey on oral health was conducted in 2,805 public preschool children aged 5 and 6 years in Piracicaba, Brazil. Children were examined by a team of ten trained dentists. It was applied a consensus technique and intra and inter agreement among examiners was assessed using the percentage of agreement. RESULTS: Of the total, 44.3% children were free of dental decay at the age of 5 and 38.5% at the age of 6. The deciduous decay teeth index (dmf-t) was 2.64 at the age of 5 and 3.07 at the age of 6, and 31.9% and 37.9%, respectively, presented dmf-t greater than 3. The largest percent of treatment need (45.3%) was surface restoration. Regarding gum health, 68.6% and 72.6% of children aged 5 and 6 years presented gum bleeding. The prevalence of fluorosis was 2.6% at the age of 5 and 6.1% at the age of 6. CONCLUSIONS: It is necessary to develop appropriate actions and strategies for higher risk groups.OBJETIVO: Verificar a prevalência de cárie, doença gengival e fluorose e dimensionar as necessidades de tratamento dos pré-escolares. MÉTODOS: Estudo transversal realizado a partir de um levantamento epidemiológico de saúde bucal em 2.805 crianças de 5 e 6 anos, matriculadas em pré-escolas municipais de Piracicaba, SP. As crianças foram examinadas por uma equipe de dez dentistas, treinados e calibrados. Foi empregada a técnica de consenso, aferindo-se o erro intra e inter examinadores pelo cálculo de percentagem de concordância. RESULTADOS: Obteve-se 44,3% de crianças livres de cárie aos 5 anos e 38,5% aos 6 anos de idade. O índice de cárie para a dentição decídua (ceo-d) foi 2,64 aos cinco anos e 3,07 aos seis anos, sendo que 31,9% e 37,9%, respectivamente, apresentaram ceo-d maior que 3. O maior percentual de necessidade de tratamento (45,3%) foi a indicação de restauração de uma superfície dentária. Quanto à saúde gengival, 68,6% e 72,6% das crianças aos 5 e 6 anos apresentaram sangramento gengival. A prevalência de fluorose observada foi de 2,6% aos 5 e 6,1% aos 6 anos. CONCLUSÕES: Há necessidade da implementação de ações e estratégias adequadas aos grupos de maior risco

Oral health among preschool children in Brazil, 1999

OBJECTIVE: To assess dental decay, gum diseases and fluorosis prevalence and evaluate treatment needs of public preschool children. METHODS: A cross-sectional epidemiological survey on oral health was conducted in 2,805 public preschool children aged 5 and 6 years in Piracicaba, Brazil. Children were examined by a team of ten trained dentists. It was applied a consensus technique and intra and inter agreement among examiners was assessed using the percentage of agreement. RESULTS: Of the total, 44.3% children were free of dental decay at the age of 5 and 38.5% at the age of 6. The deciduous decay teeth index (dmf-t) was 2.64 at the age of 5 and 3.07 at the age of 6, and 31.9% and 37.9%, respectively, presented dmf-t greater than 3. The largest percent of treatment need (45.3%) was surface restoration. Regarding gum health, 68.6% and 72.6% of children aged 5 and 6 years presented gum bleeding. The prevalence of fluorosis was 2.6% at the age of 5 and 6.1% at the age of 6. CONCLUSIONS: It is necessary to develop appropriate actions and strategies for higher risk groups.OBJETIVO: Verificar a prevalência de cárie, doença gengival e fluorose e dimensionar as necessidades de tratamento dos pré-escolares. MÉTODOS: Estudo transversal realizado a partir de um levantamento epidemiológico de saúde bucal em 2.805 crianças de 5 e 6 anos, matriculadas em pré-escolas municipais de Piracicaba, SP. As crianças foram examinadas por uma equipe de dez dentistas, treinados e calibrados. Foi empregada a técnica de consenso, aferindo-se o erro intra e inter examinadores pelo cálculo de percentagem de concordância. RESULTADOS: Obteve-se 44,3% de crianças livres de cárie aos 5 anos e 38,5% aos 6 anos de idade. O índice de cárie para a dentição decídua (ceo-d) foi 2,64 aos cinco anos e 3,07 aos seis anos, sendo que 31,9% e 37,9%, respectivamente, apresentaram ceo-d maior que 3. O maior percentual de necessidade de tratamento (45,3%) foi a indicação de restauração de uma superfície dentária. Quanto à saúde gengival, 68,6% e 72,6% das crianças aos 5 e 6 anos apresentaram sangramento gengival. A prevalência de fluorose observada foi de 2,6% aos 5 e 6,1% aos 6 anos. CONCLUSÕES: Há necessidade da implementação de ações e estratégias adequadas aos grupos de maior risco.24725

Alpha-band rhythms in visual task performance: phase-locking by rhythmic sensory stimulation

Oscillations are an important aspect of neuronal activity. Interestingly, oscillatory patterns are also observed in behaviour, such as in visual performance measures after the presentation of a brief sensory event in the visual or another modality. These oscillations in visual performance cycle at the typical frequencies of brain rhythms, suggesting that perception may be closely linked to brain oscillations. We here investigated this link for a prominent rhythm of the visual system (the alpha-rhythm, 8-12 Hz) by applying rhythmic visual stimulation at alpha-frequency (10.6 Hz), known to lead to a resonance response in visual areas, and testing its effects on subsequent visual target discrimination. Our data show that rhythmic visual stimulation at 10.6 Hz: 1) has specific behavioral consequences, relative to stimulation at control frequencies (3.9 Hz, 7.1 Hz, 14.2 Hz), and 2) leads to alpha-band oscillations in visual performance measures, that 3) correlate in precise frequency across individuals with resting alpha-rhythms recorded over parieto-occipital areas. The most parsimonious explanation for these three findings is entrainment (phase-locking) of ongoing perceptually relevant alpha-band brain oscillations by rhythmic sensory events. These findings are in line with occipital alpha-oscillations underlying periodicity in visual performance, and suggest that rhythmic stimulation at frequencies of intrinsic brain-rhythms can be used to reveal influences of these rhythms on task performance to study their functional roles

Nucleocytoplasmic transport: a thermodynamic mechanism

The nuclear pore supports molecular communication between cytoplasm and nucleus in eukaryotic cells. Selective transport of proteins is mediated by soluble receptors, whose regulation by the small GTPase Ran leads to cargo accumulation in, or depletion from the nucleus, i.e., nuclear import or nuclear export. We consider the operation of this transport system by a combined analytical and experimental approach. Provocative predictions of a simple model were tested using cell-free nuclei reconstituted in Xenopus egg extract, a system well suited to quantitative studies. We found that accumulation capacity is limited, so that introduction of one import cargo leads to egress of another. Clearly, the pore per se does not determine transport directionality. Moreover, different cargo reach a similar ratio of nuclear to cytoplasmic concentration in steady-state. The model shows that this ratio should in fact be independent of the receptor-cargo affinity, though kinetics may be strongly influenced. Numerical conservation of the system components highlights a conflict between the observations and the popular concept of transport cycles. We suggest that chemical partitioning provides a framework to understand the capacity to generate concentration gradients by equilibration of the receptor-cargo intermediary.Comment: in press at HFSP Journal, vol 3 16 text pages, 1 table, 4 figures, plus Supplementary Material include

Visual processing deficits in 22q11.2 Deletion Syndrome.

Carriers of the rare 22q11.2 microdeletion present with a high percentage of positive and negative symptoms and a high genetic risk for schizophrenia. Visual processing impairments have been characterized in schizophrenia, but less so in 22q11.2 Deletion Syndrome (DS). Here, we focus on visual processing using high-density EEG and source imaging in 22q11.2DS participants (N = 25) and healthy controls (N = 26) with an illusory contour discrimination task. Significant differences between groups emerged at early and late stages of visual processing. In 22q11.2DS, we first observed reduced amplitudes over occipital channels and reduced source activations within dorsal and ventral visual stream areas during the P1 (100-125 ms) and within ventral visual cortex during the N1 (150-170 ms) visual evoked components. During a later window implicated in visual completion (240-285 ms), we observed an increase in global amplitudes in 22q11.2DS. The increased surface amplitudes for illusory contours at this window were inversely correlated with positive subscales of prodromal symptoms in 22q11.2DS. The reduced activity of ventral and dorsal visual areas during early stages points to an impairment in visual processing seen both in schizophrenia and 22q11.2DS. During intervals related to perceptual closure, the inverse correlation of high amplitudes with positive symptoms suggests that participants with 22q11.2DS who show an increased brain response to illusory contours during the relevant window for contour processing have less psychotic symptoms and might thus be at a reduced prodromal risk for schizophrenia