mitoTALEN Eliminates Mutant mtDNA Genomes in Neurons

Mutations in the mitochondrial DNA (mtDNA) commonly cause severe encephalopathies. Because most of these mtDNA alterations are heteroplasmic, we used a mitochondrial-targeted TALEN (mitoTALEN) to specifically eliminate the mutant mtDNA in the CNS of a mouse model harboring a heteroplasmic mutation in the mitochondrial tRNA alanine gene (m.5024C>T). Delivery to neurons was achieved by using AAV-PHP.eB and neuronal expression was obtained by using a neuronal-specific synapsin promoter. We found that most CNS regions were effectively transduced and showed a significant reduction in mutant mtDNA. This reduction was accompanied by an increase in mitochondrial tRNA alanine level, which is drastically reduced by the mutation. These results showed, for the first time, that mitochondrial-targeted gene editing can be effective in reducing CNS mutant mtDNA in vivo, paving the way for clinical trials in patients with mitochondrial encephalopathies

Recent changes of water discharge and sediment load in the Yellow River basin, China

The Yellow River basin contributes approximately 6% of the sediment load from all river systems globally, and the annual runoff directly supports 12% of the Chinese population. As a result, describing and understanding recent variations of water discharge and sediment load under global change scenarios are of considerable importance. The present study considers the annual hydrologic series of the water discharge and sediment load of the Yellow River basin obtained from 15 gauging stations (10 mainstream, 5 tributaries). The Mann-Kendall test method was adopted to detect both gradual and abrupt change of hydrological series since the 1950s. With the exception of the area draining to the Upper Tangnaihai station, results indicate that both water discharge and sediment load have decreased significantly (p<0.05). The declining trend is greater with distance downstream, and drainage area has a significant positive effect on the rate of decline. It is suggested that the abrupt change of the water discharge from the late 1980s to the early 1990s arose from human extraction, and that the abrupt change in sediment load was linked to disturbance from reservoir construction.Geography, PhysicalGeosciences, MultidisciplinarySCI(E)43ARTICLE4541-5613

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Karyotype differentiation in three species of Tripogandra Raf. (Commelinaceae) with different ploidy levels

Most species of the genus Tripogandra (Commelinaceae) are taxonomically poorly circumscribed, in spite of having a relatively stable basic number x = 8. Aiming to estimate the cytological variation among Tripogandra species carrying this base number, several structural karyotypic characters were investigated in the diploid T. glandulosa, the hexaploid T. serrulata, and the octoploid T. diuretica. A careful evaluation of chromosome size and morphology did not reveal clear chromosome homeologies among karyotypes. The mean chromosome size was strongly reduced in the octoploid species, but not in the hexaploid species. They also differed largely in the CMA+ banding pattern and in the number of 5S and 45S rDNA sites per monoploid chromosome complement. All three species showed proximal DAPI + heterochromatin, although in T. serrulata this kind of heterochromatin was only visible after FISH. Further, the meiosis in T. serrulata was highly irregular, suggesting that this species has a hybrid origin. The data indicate that, in spite of the conservation of the base number, these species are karyologically quite different from each other

Genotoxic potential generated by biomass burning in the Brazilian Legal Amazon by Tradescantia micronucleus bioassay: a toxicity assessment study

<p>Abstract</p> <p>Background</p> <p>The Brazilian Amazon has suffered impacts from non-sustainable economic development, especially owing to the expansion of agricultural commodities into forest areas. The Tangará da Serra region, located in the southern of the Legal Amazon, is characterized by non-mechanized sugar cane production. In addition, it lies on the dispersion path of the pollution plume generated by biomass burning. The aim of this study was to assess the genotoxic potential of the atmosphere in the Tangará da Serra region, using <it>Tradescantia pallida </it>as <it>in situ </it>bioindicator.</p> <p>Methods</p> <p>The study was conducted during the dry and rainy seasons, where the plants were exposed to two types of exposure, active and passive.</p> <p>Results</p> <p>The results showed that in all the sampling seasons, irrespective of exposure type, there was an increase in micronucleus frequency, compared to control and that it was statistically significant in the dry season. A strong and significant relationship was also observed between the increase in micronucleus incidence and the rise in fine particulate matter, and hospital morbidity from respiratory diseases in children.</p> <p>Conclusions</p> <p>Based on the results, we demonstrated that pollutants generated by biomass burning in the Brazilian Amazon can induce genetic damage in test plants that was more prominent during dry season, and correlated with the level of particulates and elevated respiratory morbidity.</p

Postnatal depression in Southern Brazil: prevalence and its demographic and socioeconomic determinants

<p>Abstract</p> <p>Background</p> <p>Studies investigating the prevalence of postnatal depression (PND) show rates ranging from 5% to 36.7%. The investigation of age, race, educational levels, religion and income as risk factors for PND has yielded conflicting results. The aim of this study is to investigate the prevalence of PND in women residing in Southern Brazil and the associated risk factors.</p> <p>Methods</p> <p>This is population-based cross-sectional study of women residing in Porto Alegre who delivered in June 2001. A sample of 271 participants were selected from the Record of Living Newborn Infants of the State Health Department (the official Brazilian database and stores the name and address of all women who give birth to living newborn infants) using a process based on pseudo-random numbers which choose a random sample from 2.000 records. Once the addresses were identified, the women were visited at their place of residence (home, hotel, boarding house and prison), with the interviews taking place between the 6^thand the 8^thweek after delivery.</p> <p>The association between the risk factors and PND was investigated through bivariate analysis using Pearson's chi-square test. Student's t-test was used to analyze the continuous variables. To identify independent risk factors, multivariate analysis was performed using hierarchical levels with a predefined model that took into account the time relationship between PND and the risk factors. Cox's regression was used to calculate the prevalence ratios.</p> <p>Results</p> <p>The PND prevalence rate found was 20.7% (CI 95% 15.7 – 25.7). After adjusting for confounding variables, per capita income was found to have a significant association with PND.</p> <p>Conclusion</p> <p>The prevalence of PND is higher than the figures found in most developed countries and similar to the figures found in developing countries. Differences in PND by regions or countries can be partially explained by the effect of income on the mediation of risk factors. In low income populations, women should be routinely evaluated for postnatal depression, and those with no partner or spouse are likely to require further care from health services and should be given the benefit of mental health prevention programs.</p

Genome-Wide Profiling of MicroRNAs in Adipose Mesenchymal Stem Cell Differentiation and Mouse Models of Obesity

In recent years, there has been accumulating evidence that microRNAs are key regulator molecules of gene expression. The cellular processes that are regulated by microRNAs include e.g. cell proliferation, programmed cell death and cell differentiation. Adipocyte differentiation is a highly regulated cellular process for which several important regulating factors have been discovered, but still not all are known to fully understand the underlying mechanisms. In the present study, we analyzed the expression of 597 microRNAs during the differentiation of mouse mesenchymal stem cells into terminally differentiated adipocytes by real-time RT-PCR. In total, 66 miRNAs were differentially expressed in mesenchymal stem cell-derived adipocytes compared to the undifferentiated progenitor cells. To further study the regulation of these 66 miRNAs in white adipose tissue in vivo and their dependence on PPARγ activity, mouse models of genetically or diet induced obesity as well as a mouse line expressing a dominant negative PPARγ mutant were employed