regolazione epigenetica del meccanismo autonomo di fioritura in mais (Zea mays)

In the B73 maize temperate line, the autonomous flowering pathway controls flowering independently of external signals. In Arabidopsis, the epigenetic mechanisms have been demonstrated to play an important role in the control of floral transition. To understand whether, also in maize, the epigenetic mechanisms are important in the regulation of flowering, we have characterized mutants in epi-regulators that are components of the autonomous flowering pathway. Moreover, we have analyzed mutants in a key regulator of floral transition, for which a role in epigenetic mechanisms has been speculated. During the first approach, we have analyzed lines, which were simultaneously down-regulated in nfc101 and nfc102. The maize Nucleosome remodeling factor complex component101 (nfc101) and nfc102 are putative paralogs encoding WD-repeat proteins with homology to plant and mammalian components of various chromatin modifying complexes. Our results indicate that the NFC101/NFC102 proteins directly bind and repress the Indeterminate1 (Id1) and the Zea mays CENTRORADIALIS8 (ZCN8) genes, two key regulators of the autonomous flowering pathway. In addition, the abolition of NFC101/NFC102 association with repetitive sequences of different transposable elements (TEs) resulted in tissue-specific up-regulation of non-polyadenylated RNAs produced by these regions. All direct NFC101/NFC102 targets showed histone modification patterns linked to active chromatin in nfc101/nfc102 down-regulation lines. However, different mechanisms may be involved because NFC101/NFC102 proteins mediate HDAC recruitment at Id1 and TE repeats but not at ZCN8. These results, along with the pleiotropic effects observed in nfc101/nfc102 down-regulation lines, suggest that NFC101 and NFC102 are components of distinct chromatin modifying complexes, which operate in different pathways and influence diverse aspects of maize development. In the second strategy, we have analyzed id1 mutants, to understand if Id1 is able to activate ZCN8 and ZCN7 expression through epigenetic mechanisms. We have demonstrated that Id1, which is expressed in the immature leaf, partially contributes to the formation of histone modification patterns linked to active chromatin in the ZCN8 and ZCN7 loci in this tissue. So, in the immature leaf Id1 could be important for the formation of active chromatin at the ZCN8 and ZCN7 loci, which is maintained through mitotic divisions until the formation of mature leaf, where ZCN8 and ZCN7 are expressed. However, our results also indicate that other proteins could play a role in the formation of active chromatin at the ZCN8 and ZCN7 genes, independently from Id1 and could be necessary in the post-transcriptional regulation of ZCN8 and ZCN7

Multiple nuclear pseudogenes of mitochondrial cytochrome b in Ctenomys (Caviomorpha, Rodentia) with either great similarity to or high divergence from the true mitochondrial sequence

A fragment of the mitochondrial cytochrome b gene was studied in 13 species of the South American fossorial rodent Ctenomys using PCR with 'universal' primers and DNA sequencing after cloning: Five different groups of sequences were found, one of which corresponds to the functional mitochondrial gene (mt). The other four groups (A, B, C and D) were believed to be nuclear pseudogenes. Sequences A-C were highly divergent from the mt sequences and included substitutions, deletions and insertions such that they could not possibly have coded a functional protein. They all shared a common insertion between positions 15055 and 15056 suggestive of a common origin, although the A, B and C sequences otherwise differed greatly from each other. The D sequences also could not have been functional on the basis of nucleotide sequence, but the differences with the mt sequences were far more subtle and in a more limited study the D sequences could easily have been classified as a true mtDNA sequence. It is suggested that there were two transfers of the cytochrome b gene from the mitochondrion to the nucleus; the first leading to sequences A-C and the second to the D sequence. Subsequent to transfer, a sequence of duplications within the nucleus appears to have generated the full range of pseudogenes that are observed. This study adds to other recent observations suggesting the frequent transfer of mtDNA sequences to the nucleus and reinforces the necessity of great care in interpreting PCR-generated sequences, particularly those produced with universal primers. There are now data from several species of mammals and birds relating to PCR-generated nuclear copies of cytochrome b, which we review.Facultad de Ciencias Veterinaria

Multiple nuclear pseudogenes of mitochondrial cytochrome b in Ctenomys (Caviomorpha, Rodentia) with either great similarity to or high divergence from the true mitochondrial sequence

A fragment of the mitochondrial cytochrome b gene was studied in 13 species of the South American fossorial rodent Ctenomys using PCR with 'universal' primers and DNA sequencing after cloning: Five different groups of sequences were found, one of which corresponds to the functional mitochondrial gene (mt). The other four groups (A, B, C and D) were believed to be nuclear pseudogenes. Sequences A-C were highly divergent from the mt sequences and included substitutions, deletions and insertions such that they could not possibly have coded a functional protein. They all shared a common insertion between positions 15055 and 15056 suggestive of a common origin, although the A, B and C sequences otherwise differed greatly from each other. The D sequences also could not have been functional on the basis of nucleotide sequence, but the differences with the mt sequences were far more subtle and in a more limited study the D sequences could easily have been classified as a true mtDNA sequence. It is suggested that there were two transfers of the cytochrome b gene from the mitochondrion to the nucleus; the first leading to sequences A-C and the second to the D sequence. Subsequent to transfer, a sequence of duplications within the nucleus appears to have generated the full range of pseudogenes that are observed. This study adds to other recent observations suggesting the frequent transfer of mtDNA sequences to the nucleus and reinforces the necessity of great care in interpreting PCR-generated sequences, particularly those produced with universal primers. There are now data from several species of mammals and birds relating to PCR-generated nuclear copies of cytochrome b, which we review.Facultad de Ciencias Veterinaria

Travelers' vaccinations: experience from the Travelers' Clinic of Hospital das Clínicas, University of São Paulo School of Medicine

O perfil dos indivíduos, a situação vacinal e as vacinas recomendadas aos viajantes que procuram o serviço médico de orientação pré-viagem do Ambulatório dos Viajantes do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo foram analisados no presente estudo. Dos 445 viajantes estudados, 51% eram mulheres; a mediana de idade foi de 33,5 anos; 51% viajavam a trabalho e 39,5% por lazer. Destinos mais procurados: África (47%); Ásia (31,7%); América do Sul (21,4%). Trezentos e oitenta e cinco (86,5%) viajantes tiveram indicação de vacinação para viagem. Principais vacinas recomendadas: febre tifóide (55,7%), difteria-tétano (54,1%), hepatite A (46,1%), hepatite B (44,2%), febre amarela (24,7%). A orientação pré-viagem mostrou-se importante não só para indicar as vacinas recomendadas para a viagem, mas também como oportunidade para atualização das vacinas de rotina.TThe profile and vaccination status of travelers seeking pre-travel medical advice at the Travelers' Clinic of Hospital das Clínicas, University of São Paulo School of Medicine, and the vaccines recommended for them, were analyzed in the present study. Among the 445 travelers who were studied, 51% were women, the median age was 33.5 years, 51% were traveling on business and 39.5% were traveling for leisure purposes. The destinations most sought were Africa (47%), Asia (31.7%) and South America (21.4%). Vaccination before traveling was recommended for 385 (86.5%) of the travelers. The main vaccines recommended were against typhoid fever (55.7%), diphtheria-tetanus (54.1%), hepatitis A (46.1%), hepatitis B (44.2%) and yellow fever (24.7%). The pre-travel guidance was shown to be important not only for indicating the vaccines recommended for the trip, but also as an opportunity to update routine vaccinations

A northern glacial refugium for bank voles (Clethrionomys glareolus).

peer reviewedThere is controversy and uncertainty on how far north there were glacial refugia for temperate species during the Pleistocene glaciations and in the extent of the contribution of such refugia to present-day populations. We examined these issues using phylogeographic analysis of a European woodland mammal, the bank vole (Clethrionomys glareolus). A Bayesian coalescence analysis indicates that a bank vole population survived the height of the last glaciation (≈25,000–10,000 years B.P.) in the vicinity of the Carpathians, a major central European mountain chain well north of the Mediterranean areas typically regarded as glacial refugia for temperate species. Parameter estimates from the fitted isolation with migration model show that the divergence of the Carpathian population started at least 22,000 years ago, and it was likely followed by only negligible immigration from adjacent regions, suggesting the persistence of bank voles in the Carpathians through the height of the last glaciation. On the contrary, there is clear evidence for gene flow out of the Carpathians, demonstrating the contribution of the Carpathian population to the colonization of Europe after the Pleistocene. These findings are consistent with data from animal and plant fossils recovered in the Carpathians and provide the clearest phylogeographic evidence to date of a northern glacial refugium for temperate species in Europe

Occurrence of Early Adverse Events After Vaccination Against Influenza at a Brazilian Reference Center

INTRODUCTION: Since 1999, the Ministry of Health in Brazil has conducted campaigns of vaccination against influenza targeted towards the elderly, chronically-diseased people and health care workers. The vaccine against influenza is associated with adverse events of minor importance. OBJECTIVE: To investigate the early adverse events related to the vaccine against influenza. CASUISTICS AND METHODS: One hundred and ninety seven elderly individuals and health care workers vaccinated against influenza were included. An inquiry regarding adverse events related to the vaccine was applied seven days after the vaccination. RESULTS: Local adverse events were reported by 32.5% and systemic effects by 26.4% of the vaccinated subjects. Pain in the region of the injection, headache, myalgia, malaise, and coryza were more frequent in the workers than in the elderly (p<0.05). There was no statistically significant difference in the occurrence of fever. CONCLUSIONS: The belief of part of the population that credits frequent and uncomfortable adverse events to the vaccine was not confirmed. The subjective adverse events were more frequent in the health care workers, which can influence, in a negative way, the disclosure of the benefits of this vaccine due to their role as opinion makers

Multiple nuclear pseudogenes of mitochondrial cytochrome b in Ctenomys (Caviomorpha, Rodentia) with either great similarity to or high divergence from the true mitochondrial sequence

A fragment of the mitochondrial cytochrome b gene was studied in 13 species of the South American fossorial rodent Ctenomys using PCR with 'universal' primers and DNA sequencing after cloning: Five different groups of sequences were found, one of which corresponds to the functional mitochondrial gene (mt). The other four groups (A, B, C and D) were believed to be nuclear pseudogenes. Sequences A-C were highly divergent from the mt sequences and included substitutions, deletions and insertions such that they could not possibly have coded a functional protein. They all shared a common insertion between positions 15055 and 15056 suggestive of a common origin, although the A, B and C sequences otherwise differed greatly from each other. The D sequences also could not have been functional on the basis of nucleotide sequence, but the differences with the mt sequences were far more subtle and in a more limited study the D sequences could easily have been classified as a true mtDNA sequence. It is suggested that there were two transfers of the cytochrome b gene from the mitochondrion to the nucleus; the first leading to sequences A-C and the second to the D sequence. Subsequent to transfer, a sequence of duplications within the nucleus appears to have generated the full range of pseudogenes that are observed. This study adds to other recent observations suggesting the frequent transfer of mtDNA sequences to the nucleus and reinforces the necessity of great care in interpreting PCR-generated sequences, particularly those produced with universal primers. There are now data from several species of mammals and birds relating to PCR-generated nuclear copies of cytochrome b, which we review.Facultad de Ciencias Veterinaria

Association between polymorphism in IgG Fc receptor IIIa coding gene and biological response to infliximab in Crohn's disease

AIM: To test the hypothesis of an association between polymorphism in FCGR3A (the gene coding for FcgammaRIIIa, which is expressed on macrophages and natural killer cells, is involved in antibody-dependent cell-mediated cytotoxicity and has recently been associated with a positive response to rituximab, a recombinant immunoglobulin G1 antibody used in non-Hodgkin's lymphomas) and response to infliximab in Crohn's disease. METHODS: FCGR3A-158 polymorphism was determined using an allele-specific polymerase chain reaction assay in 200 Crohn's disease patients who had received infliximab for either refractory luminal (n = 142) or fistulizing (n = 58) Crohn's disease. Clinical and biological responses (according to C-reactive protein levels) were assessed in 200 and 145 patients, respectively. RESULTS: There were 82.9% clinical responders in V/V patients vs. 72.7% in V/F and F/F patients (N.S.). Globally, the decrease in C-reactive protein was significantly higher in V/V patients than in F carriers (P = 0.0078). A biological response was observed in 100% of V/V patients, compared with 69.8% of F carriers (P = 0.0002; relative risk, 1.43; 95% confidence interval, 1.27-1.61). In the sub-group of patients with elevated C-reactive protein before treatment, the multivariate analysis selected the use of immunosuppressive drugs and FCGR3A genotype as independent factors influencing the clinical response to infliximab (P = 0.003). CONCLUSION: Crohn's disease patients with FCGR3A-158 V/V genotype have a better biological and, possibly, clinical response to infliximab

Complex effects of dyslexia risk factors account for ADHD-traits : evidence from two independent samples

Background: Developmental dyslexia (DD) and attention deficit/hyperactivity disorder (ADHD) are among the most common neurodevelopmental disorders, whose etiology involves multiple risk factors. DD and ADHD co-occur in the same individuals much more often than would be expected by chance. Several studies have found significant bivariate heritability, and specific genes associated with either DD or ADHD have been investigated for association in the other disorder. Moreover, there are likely to be gene-by-gene and gene-by-environment interaction effects (GxG and GxE, respectively) underlying the comorbidity between DD and ADHD. We investigated the pleiotropic effects of 19 SNPs spanning five DD genes (DYX1C1, DCDC2, KIAA0319, ROBO1 and GRIN2B) and seven DD environmental factors (smoke, miscarriage, birth weight, breastfeeding, parental age, socioeconomic status and parental education) for main, either 1) genetic or 2) environmental, 3) G×G, and 4) G×E upon inattention and hyperactivity/impulsivity. We then attempted replication of these findings in an independent twin cohort. Methods: Marker-trait association was analyzed by implementing the Quantitative Transmission Disequilibrium Test (QTDT). Environmental associations were tested by partial correlations. GxG were investigated by a general linear model equation and a family-based association test. GxE were analyzed through a general test for GxE in sib-pair-based association analysis of quantitative traits. Results: DCDC2-rs793862 was associated with hyperactivity/impulsivity via G×G (KIAA0319) and G×E (miscarriage). Smoke was significantly correlated with hyperactivity/impulsivity. We replicated the DCDC2×KIAA0319 interaction upon hyperactivity/impulsivity in the twin cohort. Conclusions: DD genetic (DCDC2) and environmental factors (smoke and miscarriage) underlie ADHD-traits supporting a potential pleiotropic effect