A fresh look at mycobacterial pathogenicity with the zebrafish host model

The zebrafish has earned its place among animal models to study tuberculosis and other infections caused by pathogenic mycobacteria. This model host is especially useful to study the role of granulomas, the inflammatory lesions characteristic of mycobacterial disease. The optically transparent zebrafish larvae provide a window on the initial stages of granuloma development in the context of innate immunity. Application of fluorescent dyes and transgenic markers enabled real-time visualization of how innate immune mechanisms, such as autophagy and inflammasomes, are activated in infected macrophages and how propagating calcium signals drive communication between macrophages during granuloma formation. A combination of imaging, genetic, and chemical approaches has revealed that the interplay between macrophages and mycobacteria is the main driver of tissue dissemination and granuloma development, while neutrophils have a protective function in early granulomas. Different chemokine signaling axes, conserved between humans and zebrafish, have been shown to recruit macrophages permissive to mycobacterial growth, control their microbicidal capacity, drive their spreading and aggregation, and mediate granuloma vascularization. Finally, zebrafish larvae are now exploited to explore cell death processes, emerging as crucial factors in granuloma expansion. In this review, we discuss recent advances in the understanding of mycobacterial pathogenesis contributed by zebrafish models.Animal science

Resource use efficiency is affected by phytoplankton community changes and geochemical shifts over time in a coastal upwelling area (NE Atlantic).

abstractTime series records are crucial to understand the dynamical processes that occur within phytoplankton communities. This is even more important in the context of the current global change that is already forcing alterations of unprecedented nature and might have unknown consequences for multiple ecosystem processes. Here we present time series analyses of the biogeochemical trends that occurred in the shelf of the Galician coast (station 2 off A Coruña, NE Atlantic) since late 1980s. Upwelling strength and sea temperature in the area have not changed substantially during the last decades. However, while nitrate fertilization from upwelled waters has remained relatively stable, phosphate concentration has increased leading to a negative trend in the N:P ratio. Those trends have impacted the phytoplankton resource use efficiency jointly with the evenness of the community. Phytoplankton used resources more efficiently at higher values of upwelling strength and at lower values of nutrient concentration and evenness. Phytoplankton communities that were more even had higher dinoflagellate diversity contrasting to dominance of diatoms that used resources more efficiently. Moreover, variability in resource use efficiency increased with evenness.IEO (RADIALES-11

Estudio de la obesidad y del sobrepeso como factores de riesgo de la prevalencia y severidad del asma en niños de Valencia

[email protected]; [email protected]; [email protected]: La obesidad y el sobrepeso se han descrito como factores de riesgo asociados a la prevalencia y severidad del asma en niños y adolescentes. El objetivo del estudio ha sido el valorar el papel de la obesidad en el asma infantil. Ámbito de estudio y sujetos:Estudio realizado en niños y adolescentes entre 8 y 15 años, elegidos por un muestreo aleatorio tipo cluster entre los niños que estudiaban en 80 colegios, el cual representa el 30% de los colegios de la ciudad de Valencia. Material y métodos:El análisis de los datos se organizó en dos grupos, obesos (aquellos niños en un percentil superior al 85 del Índice de Masa Corporal (kg/m2), tomando como referencia la población española) y no obesos, cuando no cumplian esta condición. Se calcularon la prevalencia de los diferentes parámetros con un intervalo de confianza al 95%, y el riesgo relativo (RR) de los síntomas compatibles con asma entre niños obesos comparándolos con los no obesos. Resultados: No se obtuvo un riesgo relativo significativo para la obesidad con respecto al asma en aquellos niños por encima del percentil 85. Por otra parte, un incremento en el riesgo en relación con la severidad del asma se observó con la obesidad, principalmente en el percentil 85 (RR = 1,51 de sufrir entre 4-12 ataques de pitos y RR = 1,86 de sufrir más de 12 ataques en niños obesos frente a los no obesos) Conclusiónes: En este estudio, no identificamos un riesgo más alto de asma entre niños obesos frente a los no obesos, aunque encontramos que hubiera un riesgo más alto de severidad de síntomas asmáticos. En relación con la severidad del asma, observamos un riesgo más alto de ataques de pitos y sibilancias entre los niños obesos en los percentiles 85 y 95 del Indice de Masa Corporal.Background: Obesity and overweight have been described as factors associated with asthma. Our aim was to evaluate the role obesity plays on asthma in children. Scope and subjects: A study carried out on children and teenagers between 8 and 15 years of age, chosen for a cluster-type random sampling from children who studied in 80 schools, which represents 30% of the schools in the city of Valencia. Material and Methods: The analysed data was organized into two groups, obese (from the Body Mass Index (Kg/m2)), showing children with a percentile over 85% of the measuring reference for the Spanish population) and non obese, when they did not fulfil this condition. The prevalence of the different parameters studied was calculated by an Interval of Confidence of 95%. The risk was calculated (Relative Risk) from those symptoms compatible with asthma among obese children compared to non obese children. Results: No significant relative risk (RR) was seen for obesity with regards to asthma in those percentiles of obesity over 85. Otherwise, an increase in the relative risk (RR) regarding the severity of asthma was seen in relation to obesity, mainly in the 85th percentile (RR = 1.51 of suffering between 4-12 wheezing attacks and RR = 1.86 of suffering more than 12 attacks in obese children as opposed to non obese children). Conclusions: In this study, we did not identify a higher risk of asthma among obese children than among non obese children, although we did find there was a higher risk of severity of asthmatic symptoms. As far as the severity of the asthma is concerned, we saw a higher risk of wheezing and whistling attacks among obese children with the 85th and the 95th percentiles according to the Body Mass [email protected]; [email protected]; [email protected]

LAPped in proof: LC3‐associated phagocytosis and the arms race against bacterial pathogens

Cells of the innate immune system continuously patrol the extracellular environment for potential microbial threats that are to be neutralized by phagocytosis and delivery to lysosomes. In addition, phagocytes employ autophagy as an innate immune mechanism against pathogens that succeed to escape the phagolysosomal pathway and invade the cytosol. In recent years, LC3-associated phagocytosis (LAP) has emerged as an intermediate between phagocytosis and autophagy. During LAP, phagocytes target extracellular microbes while using parts of the autophagic machinery to label the cargo-containing phagosomes for lysosomal degradation. LAP contributes greatly to host immunity against a multitude of bacterial pathogens. In the pursuit of survival, bacteria have developed elaborate strategies to disarm or circumvent the LAP process. In this review, we will outline the nature of the LAP mechanism and discuss recent insights into its interplay with bacterial pathogens.Animal science

Terminal 18q deletions are stabilized by neotelomeres

Background: All human chromosomes are capped by tandem repeat (TTAGGG)n sequences that protect them against end-to-end fusion and are essential to chromosomal replication and integrity. Therefore, after a chromosomal breakage, the deleted chromosomes must be stabilized by retaining the telomere or acquiring a new cap, by telomere healing or telomere capture. There are few reports with molecular approaches on the mechanisms involved in stabilization of 18q terminal deletions.Results: in this study we analyzed nine patients with 18q terminal deletion identified by G-banding and genomic array. FISH using PNA probe revealed telomeric signals in all deleted chromosomes tested. We fine-mapped breakpoints with customized arrays and sequenced six terminal deletion junctions. in all six deleted chromosomes sequenced, telomeric sequences were found directly attached to the breakpoints. Little or no microhomology was found at the breakpoints and none of the breaks sequenced were located in low copy repeat (LCR) regions, though repetitive elements were found around the breakpoints in five patients. One patient presented a more complex rearrangement with two deleted segments and an addition of 17 base pairs (bp).Conclusions: We found that all six deleted chromosomes sequenced were probably stabilized by the healing mechanism leading to a neotelomere formation.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Morphol & Genet, BR-04023900 São Paulo, BrazilEmory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USAUniversidade Federal de São Paulo, Dept Biophys, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, Lab Citogenom, BR-05403000 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, Lab Citogenom, BR-05403000 São Paulo, BrazilFAPESP: 2012/51150-0FAPESP: 2012/15572-7Web of Scienc

The role of family in the intergenerational transmission of collective action

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordThe present research demonstrates intergenerational influences on collective action participation, whereby parents’ past and current participation in collective action (descriptive family norms) shape their children’s participation in conventional and radical collective action via injunctive family norms (perception that parents value such participation). Two unique data sets were used: dyads of activist parents and their adult children (Study 1, N = 100 dyads) and student activists who participated in a yearlong, three-wave longitudinal study (Study 2, Ns wave 1 = 1,221, Wave 2 = 960, and Wave 3 = 917). Parents’ past and current participation directly and indirectly predicted children’s protest participation in Study 1, while Study 2 showed a similar pattern longitudinally: Perceptions of parents’ participation (descriptive family norm) and approval (injunctive family norm) predicted change in collective action participation over time. Together, results highlight family environment as a critical setting for the intergenerational transmission of protest

ME20-S as a Potential Biomarker for the Evaluation of Uveal Melanoma

PURPOSE: We previously identified the presence of the melanocyte-specific secreted (ME20-S) glycoprotein in secretomes of uveal melanoma (UM) cultures. The aim of this study was to test for the presence and levels of ME20-S in the serum of patients with choroidal nevi and UM and correlate these levels with individual clinical data. METHODS: Serum ME20-S levels were determined by ELISA in 111 patients distributed into four categories (53 choroidal nevi, 30 untreated UM, 11 10-year disease-free [DF] UM, 17 hepatic metastatic UM) and 32 age- and sex-matched controls. ME20-S levels were correlated with individual clinical data. RESULTS: The UM and the metastatic groups showed significantly higher levels of serum ME20-S than the other groups (P < 0.001). ME20-S levels in the DF patients did not differ from those in the control group. In addition, log-transformed serum ME20-S levels showed a positive correlation with the thickness of the lesion mass in UM patients (regression coefficient 0.0689, 95% confidence interval 0.0689-0.1123, R2 = 27.1%). CONCLUSIONS: Elevated ME20-S serum levels are associated with tumor size and advanced stages of UM while low levels are characteristic of DF patients. ME20-S might be a promising serum marker for UM and useful for monitoring metastatic disease

Investigation of selected genomic deletions and duplications in a cohort of 338 patients presenting with syndromic obesity by multiplex ligation-dependent probe amplification using synthetic probes

Background: Certain rare syndromes with developmental delay or intellectual disability caused by genomic copy number variants (CNVs), either deletions or duplications, are associated with higher rates of obesity. Current strategies to diagnose these syndromes typically rely on phenotype-driven investigation. However, the strong phenotypic overlap between syndromic forms of obesity poses challenges to accurate diagnosis, and many different individual cytogenetic and molecular approaches may be required. Multiplex ligation-dependent probe amplification (MLPA) enables the simultaneous analysis of multiple targeted loci in a single test, and serves as an important screening tool for large cohorts of patients in whom deletions and duplications involving specific loci are suspected. Our aim was to design a synthetic probe set for MLPA analysis to investigate in a cohort of 338 patients with syndromic obesity deletions and duplications in genomic regions that can cause this phenotype.Results: We identified 18 patients harboring copy number imbalances; 18 deletions and 5 duplications. the alterations in ten patients were delineated by chromosomal microarrays, and in the remaining cases by additional MLPA probes incorporated into commercial kits. Nine patients showed deletions in regions of known microdeletion syndromes with obesity as a clinical feature: in 2q37 (4 cases), 9q34 (1 case) and 17p11.2 (4 cases). Four patients harbored CNVs in the DiGeorge syndrome locus at 22q11.2. Two other patients had deletions within the 22q11.2 'distal' locus associated with a variable clinical phenotype and obesity in some individuals. the other three patients had a recurrent CNV of one of three susceptibility loci: at 1q21.1 'distal', 16p11.2 'distal', and 16p11.2 'proximal'.Conclusions: Our study demonstrates the utility of an MLPA-based first line screening test to the evaluation of obese patients presenting with syndromic features. the overall detection rate with the synthetic MLPA probe set was about 5.3% (18 out of 338). Our experience leads us to suggest that MLPA could serve as an effective alternative first line screening test to chromosomal microarrays for diagnosis of syndromic obesity, allowing for a number of loci (e.g., 1p36, 2p25, 2q37, 6q16, 9q34, 11p14, 16p11.2, 17p11.2), known to be clinically relevant for this patient population, to be interrogated simultaneously.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ São Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, Human Genome & Stem Cell Ctr, São Paulo, BrazilUniv São Paulo, Sch Med, Children Inst, Genet Unit,Dept Pediat, São Paulo, BrazilUniv São Paulo, Sch Med, Dept Med Genet, Neurogenet Unit, BR-14049 Ribeirao Preto, BrazilUniversidade Federal de São Paulo, Ctr Med Genet, Dept Morphol, São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Med Genet, Dept Morphol, São Paulo, BrazilFAPESP: 09/52523-1FAPESP: 1998/14254-2CNPq: 304381/2007-1Web of Scienc