Journals
2013 EN
Davide Bernardi · Benjamin Lindner
The coherence function of integrate-and-fire neurons shows low-pass properties in the most diverse firing regimes [1]. While the coherence function provides a good approximation to the full information transfer properties in the case of a weak input, for a strong input non-linear encoding could play an important role. The complete information transfer is quantified by Shannon's mutual information rate [2] which has been estimated in certain biological model systems [3]. In general, the exact analytical calculation of the mutual information rate is unfeasible and even the numerical estimation is demanding [4]. Numerical calculation of the mutual information rate is now a commonly adopted practice, but it does not indicate what aspects of the stimulus are best represented by the neuronal response. We developed a numerical procedure to directly calculate a frequency-selective version of the mutual information rate. This can be used to study how different frequency components of a Gaussian stimulus are encoded in neural models without invoking a weak-signal paradigm.
Journals
2013 EN
YongIk Kwon · K. Abe · M. Endo
+6 more
Background Mammalian BLM helicase is involved in DNA replication, DNA repair and homologous recombination (HR). These DNA transactions are associated tightly with cell division and are important for maintaining genome stability. However, unlike in mammals, cell division in higher plants is restricted mainly to the meristem, thus genome maintenance at the meristem is critical. The counterpart of BLM in Arabidopsis ( AtRecQ4A ) has been identified and its role in HR and in the response to DNA damage has been confirmed. However, the function of AtRecQ4A in the meristem during replication stress has not yet been well elucidated. Results We isolated the BLM counterpart gene OsRecQl4 from rice and analyzed its function using a reverse genetics approach. Osrecql4 mutant plants showed hypersensitivity to DNA damaging agents and enhanced frequency of HR compared to wild-type (WT) plants. We further analyzed the effect of aphidicolin—an inhibitor of S-phase progression via its inhibitory effect on DNA polymerases—on genome stability in the root meristem in osrecql4 mutant plants and corresponding WT plants. The following effects were observed upon aphidicolin treatment: a) comet assay showed induction of DNA double-strand breaks (DSBs) in mutant plants, b) TUNEL assay showed enhanced DNA breaks at the root meristem in mutant plants, c) a recombination reporter showed enhanced HR frequency in mutant calli, d) propidium iodide (PI) staining of root tips revealed an increased incidence of cell death in the meristem of mutant plants. Conclusions These results demonstrate that the aphidicolin-sensitive phenotype of osrecql4 mutants was in part due to induced DSBs and cell death, and that OsRecQl4 plays an important role as a caretaker, maintaining genome stability during DNA replication stress in the rice meristem.
Journals
2013 EN
Érika Cardoso dos Reis · Gisele O’Dwyer
Background Two policies stood out in the 2000s geared towards changing the care model adopted in Brazil: The National Policy on Primary Health Care, based on a family health care model, and the National Policy on Health Promotion. The aim of this study was to analyze health promotion actions developed by family health care teams in the municipality of Belford Roxo. This town was chosen by virtue of its “below average” level of primary health care services offered in relation to other municipalities in Rio de Janeiro state. Methods The following methodological strategies were employed: analysis of health systems, document analysis (2010 Annual Health Schedule and 2010 Annual Management Report), participant observation and interviews with nine health care professionals in the region of study, namely: the manager of the Regional Health Polyclinic (responsible for health care actions in the region), and nurses belonging to the eight family health teams. Giddens’ Theory of Structuration was used for analysis of the results. Results Varying levels of health care activity were found, indicating that the managers have been either unable or lacked the commitment to perform the proposed actions. From a structural point of view, 87.5% of the teams were incomplete. Also of particular note was the lack of any physicians in the teams, which, despite its detrimental effect, was regarded by the interviewees as “natural”. Strong political party influence in the area hindered relations between the team and the local population. Health education, especially through lectures was the main health promotion activity picked up in this study. No cross-sectorial or public participation actions were identified. Connections between the teams for sharing responsibilities were found to be very weak. Conclusion In addition to political factors, there are also structural limitations such as a lack of human resources that overburdens the teams’ daily activities. From this point of view, the political context and lack of professionals were restrictive factors for health promotion. Belford Roxo is not necessarily representative of other experiences in Brazil. However, problems such as patronage, political manipulation, poverty and incipient cross-sectorial actions are common to other Brazilian towns and cities.
Springer Science+Business Media
Journals
2013 EN
Érika Calvano Küchler · Kathleen Deeley · Bao Ho
+20 more
Background Our previous genome-wide linkage scan mapped five loci for caries experience. The purpose of this study was to fine map one of these loci, the locus 13q31.1, in order to identify genetic contributors to caries. Methods Seventy-two pedigrees from the Philippines were studied. Caries experience was recorded and DNA was extracted from blood samples obtained from all subjects. Sixty-one single nucleotide polymorphisms (SNPs) in 13q31.1 were genotyped. Association between caries experience and alleles was tested. We also studied 1,481 DNA samples obtained from saliva of subjects from the USA, 918 children from Brazil, and 275 children from Turkey, in order to follow up the results found in the Filipino families. We used the AliBaba2.1 software to determine if the nucleotide changes of the associated SNPs changed the prediction of the presence of transcription-binding site sequences and we also analyzed the gene expression of the genes selected based on binding predictions. Mutation analysis was also performed in 33 Filipino individuals of a segment of 13q31.1 that is highly conserved in mammals. Results Statistically significant association with high caries experience was found for 11 markers in 13q31.1 in the Filipino families. Haplotype analysis also confirmed these results. In the populations used for follow-up purposes, associations were found between high caries experience and a subset of these markers. Regarding the prediction of the transcription-binding site, the base change of the SNP rs17074565 was found to change the predicted-binding of genes that could be involved in the pathogenesis of caries. When the sequence has the allele C of rs17074565, the potential transcription factors binding the sequence are GR and GATA1 . When the subject carries the G allele of rs17074565, the potential transcription factor predicted to bind to the sequence is GATA3 . The expression of GR in whole saliva was higher in individuals with low caries experience when compared to individuals with high caries experience (p = 0.046). No mutations were found in the highly conserved sequence. Conclusions Genetic factors contributing to caries experience may exist in 13q31.1. The rs17074565 is located in an intergenic region and is predicted to disrupt the binding sites of two different transcription factors that might be involved with caries experience. GR expression in saliva may be a biomarker for caries risk and should be further explored.
Journals
2013 EN
Érika Barbosa Camargo · Luci Fabiane Scheffer Moraes · Celsa da Silva Moura Souza
+5 more
Background Preeclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide and especially in Latin America. High quality evidence indicates that calcium supplementation during pregnancy significantly reduces the incidence of preeclampsia and its consequences, including severe maternal morbidity and death. Few studies have assessed the implementation of this intervention in clinical practice. The study aimed to assess the proportion of pregnant women who received calcium supplements in Brazilian public antenatal care clinics. Methods This cross-sectional study interviewed women waiting for antenatal care visits in 9 public clinics in 4 Brazilian cities in 2010-2012. Trained interviewers used a standardized anonymous questionnaire to collect socio demographic and obstetric data, information on ingestion of dairy products and on prescriptions received during current pregnancy. Results A total of 788 valid questionnaires were analyzed. Participants were young (mean age 25.9), mostly multiparous (71.3%) and in the 2 nd or 3 rd trimesters of pregnancy at the time of interview (87.6%). Only 5.1% (40/788) had received a prescription for calcium supplements. Based on their reported ingestion of dairy products, the mean daily dietary calcium intake of the participants was 210 (+ 265) mg/day and over 90% consumed less than 1 g of calcium/day. Conclusions Despite good quality evidence indicating the benefits of this practice especially for women with low calcium diets, less than 6% of a sample of women receiving antenatal care in Brazilian public clinics received a prescription for calcium supplements. There is an urgent need to upscale the implementation of this life-saving intervention.
Journals
2013 EN
Akemi Tomoda · Shota Nishitani · Naomi Matsuura
+5 more
Background Identification of gene × environment interactions (G × E) for depression is a crucial step in ascertaining the mechanisms underpinning the disorder. Earlier studies have indicated strong genetic influences and numerous environmental risk factors. In relation to childhood and adolescent depression, evidence is accumulating that the quality of the parental environment is associated with serotonin biology in children. We hypothesized that maternal depression is a crucial environmental risk factor associated with serotonin-regulating genes. Methods This study was designed to ascertain the G × E interaction for diagnosis of depression in a Japanese pediatric sample. DNA samples from 55 pediatric patients with depression and 58 healthy schoolchildren were genotyped for the 5-HTT (2 short (S) alleles at the 5-HTT locus) promoter serotonin-transporter-linked polymorphic region ( 5-HTTLPR ) polymorphism. We examined whether an adverse parental environment, operationalized as the mother’s history of recurrent major depressive disorder, interacts with 5-HTTLPR polymorphism to predict patients’ depression symptoms. Results Binary logistic regression analyses revealed that maternal depression (adversity), gender, and FSIQ significantly affect the diagnosis of depression among children and adolescents. However, no main effect was found for adversity or genotype. Results of multivariable logistic regression analyses using stepwise procedure have elicited some models with a good fit index, which also suggests no interaction between 5-HTTLPR and adversity on depression. Conclusions To assess G × E interaction, data obtained from children and adolescents who had been carefully diagnosed categorically and data from age-matched controls were analyzed using logistic regression. Despite an equivocal interaction effect, adversity and gender showed significant main effects.
Journals
2013 EN
Minako Kawabata · Taro Ueno · Jun Tomita
+4 more
Background Accumulating evidence has shown a universality in the temporal organization of activity and rest among animals ranging from mammals to insects. Previous reports in both humans and mice showed that rest bout durations followed long-tailed (i.e., power-law) distributions, whereas activity bouts followed exponential distributions. We confirmed similar results in the fruit fly, Drosophila melanogaster . Conversely, another report showed that the awakening bout durations, which were defined by polysomnography in bed, followed power-law distributions, while sleeping periods, which may correspond to rest, followed exponential distributions. This apparent discrepancy has been left to be resolved. Methods Actigraphy data from healthy and disordered children were analyzed separately for two periods: time out of bed (UP period) and time in bed (DOWN period). Results When data over a period of 24 h were analyzed as a whole, rest bouts showed a power law distribution as previously reported. However, when UP and DOWN period data were analyzed separately, neither showed power law properties. Using a newly developed strict method, only 30% of individuals satisfied the power law criteria, even when the 24 h data were analyzed. The human results were in contrast to the Drosophila results, which revealed clear power-law distributions for both day time and night time rest through the use of a strict method. In addition, we analyzed the actigraphy data from patients with childhood type chronic fatigue syndrome (CCFS), and found that they showed differences from healthy controls when their UP and DOWN data were analyzed separately. Conclusions These results suggested that the DOWN sleep, the bout distribution of which showed exponential properties, contributes to the production of long-tail distributions in human rest periods. We propose that separate analysis of UP and DOWN period data is important for understanding the temporal organization of activity.
Journals
2013 EN
Chiyako Oshikata · Naomi Tsurikisawa · Akemi Saito
+8 more
Background Penicillium species are among the most common fungi present in the environment and are usually considered non-pathogenic to humans. However, in immunocompromised hosts they can be virulent pathogens and can cause death. Penicillium digitatum is a plant pathogen that commonly causes a postharvest fungal disease of citrus called green mould; it very rarely causes systemic mycosis in humans. Here, we report a case of fatal pneumonia due to P. digitatum infection, as confirmed by repeated examination of cultured sputum. Case presentation A cavity was found in the left upper lung on routine chest X-ray in a 78-year-old undernourished male who had been diagnosed at age 66 with bronchial asthma and pulmonary emphysema. No increased sputum production was present. The presence of antigen-specific precipitating antibodies to Aspergillus flavus and P. digitatum was confirmed in the patient’s serum and also later pleural fluid by using Ouchterlony double immunodiffusion testing with A. flavus and P. digitatum antigens. The patient was treated over a period of months with itraconazole, micafungin, voriconazole, amphotericin B, and antibacterials. However, the cavity enlarged, the pleural effusion increased, and the patient began producing purulent sputum. He died from progressive renal failure. From sputum culture only one fungus was isolated repeatedly on potato-dextrose agar in large quantities. This fungus was confirmed to be P. digitatum by molecular identification. Partial sequences of the beta-tubulin gene were determined by using the primers Bt2a and Bt2b for PCR amplification and sequencing and underwent a BLAST search at the National Centre for Biotechnology Information, these results confirmed that the isolated fungus was P. digitatum . Conclusion To our knowledge, this is the first report of pulmonary infection with P. digitatum . Our patient had pulmonary emphysema and was elderly, and undernourished. These factors might have facilitated the infection. In his case, antimycotics were ineffective in treating the lung involvement. Although human infection with P. digitatum is considered rare, it appears that this organism can be very virulent and resistant to antimycotics.
Journals
2013 EN
Sylene Coutinho Rampche de Carvalho · Maria Tereza Cartaxo Muniz · Maria Deozete Vieira Siqueira
+7 more
Background Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, which includes a spectrum of hepatic pathology such as simple steatosis, steatohepatitis, fibrosis and cirrhosis. The increased serum levels of homocysteine (Hcy) may be associated with hepatic fat accumulation. Genetic mutations in the folate route may only mildly impair Hcy metabolism. The aim of this study was to investigate the relation between liver steatosis with plasma homocysteine level and MTHFR C677T and A1298C polymorphisms in Brazilian patients with NAFLD. Methods Thirty-five patients diagnosed with NAFLD by liver biopsy and forty-five healthy controls neither age nor sex matched were genotyped for C677T and A1298C MTHFR polymorphisms using PCR-RFLP and PCR-ASA, respectively, and Hcy was determined by HPLC. All patients were negative for markers of Wilson’s, hemochromatosis and autoimmune diseases. Their daily alcohol intake was less than 100 g/week. A set of metabolic and serum lipid markers were also measured at the time of liver biopsies. Results The plasma Hcy level was higher in NAFLD patients compared to the control group (p = 0.0341). No statistical difference for genotypes 677C/T (p = 0.110) and 1298A/C (p = 0.343) in patients with NAFLD and control subjects was observed. The genotypes distribution was in Hardy-Weinberg equilibrium (677C/T p = 0.694 and 1298 A/C p = 0.188). The group of patients and controls showed a statistically significant difference (p 0.05). The suggested genetic susceptibility to the MTHFR C677T and A1298C should be confirmed in large population based studies.
Journals
2013 EN
M Indinnimeo · Alessio Impagnatiello · Gabriella d’Ettorre
+8 more
Treatment of anorectal Buschke-Löwenstein tumor (BLT) with squamous cell carcinoma (SCC) transformation is not univocal given the rarity of the disease. BLT is characterized by its large size and tendency to infiltrate into underlying tissues. Malignant transformation can occur and it is important to identify the presence of neoplastic foci to decide the proper treatment. Our aim was to assess the effectiveness of neo-adjuvant chemo-radiation therapy (CRT) and local excision in order to avoid abdomino-perineal resection (APR). Three cases of anorectal BLT with SCC transformation are presented. All patients were HIV positive and treated with antiretroviral drugs. They underwent preoperative endoanal ultrasound, biopsies, total body tomography and anal brushing. Treatment consisted of neo-adjuvant chemo-radiation therapy (45 Gy to the pelvis plus a boost with 14.40 Gy to the primary tumor for a total of 59.40 Gy, and mitomycin-C in bolus on the first day, plus 5-fluorouracil by continuous infusion in the first and in the sixth week) and subsequent local surgical excision. During the follow-up, patients were subjected to the same preoperative diagnostic investigations and high resolution anoscopy. All patients showed a complete regression of the lesion after CRT and were treated by local surgical excision, thus avoiding permanent colostomy. In conclusion neo-adjuvant chemo-radiation therapy with local surgical excision could be considered an effective therapy in the treatment of anorectal BLT with SCC transformation to avoid APR.