Gene Expression Analysis of Forskolin Treated Basilar Papillae Identifies MicroRNA181a as a Mediator of Proliferation

Auditory hair cells spontaneously regenerate following injury in birds but not mammals. A better understanding of the molecular events underlying hair cell regeneration in birds may allow for identification and eventually manipulation of relevant pathways in mammals to stimulate regeneration and restore hearing in deaf patients.Gene expression was profiled in forskolin treated (i.e., proliferating) and quiescent control auditory epithelia of post-hatch chicks using an Affymetrix whole-genome chicken array after 24 (n = 6), 48 (n = 6), and 72 (n = 12) hours in culture. In the forskolin-treated epithelia there was significant (p<0.05; >two-fold change) upregulation of many genes thought to be relevant to cell cycle control and inner ear development. Gene set enrichment analysis was performed on the data and identified myriad microRNAs that are likely to be upregulated in the regenerating tissue, including microRNA181a (miR181a), which is known to mediate proliferation in other systems. Functional experiments showed that miR181a overexpression is sufficient to stimulate proliferation within the basilar papilla, as assayed by BrdU incorporation. Further, some of the newly produced cells express the early hair cell marker myosin VI, suggesting that miR181a transfection can result in the production of new hair cells.These studies have identified a single microRNA, miR181a, that can cause proliferation in the chicken auditory epithelium with production of new hair cells

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Metal contamination in benthic macroinvertebrates in a sub-basin in the southeast of Brazil

Benthic macroinvertebrates have many useful properties that make possible the use of these organisms as sentinel in biomonitoring programmes in freshwater. Combined with the characteristics of the water and sediment, benthic macroinvertebrates are potential indicators of environmental quality. Thus, the spatial occurrence of potentially toxic metals (Al, Zn, Cr, Co, Cu, Fe, Mn and Ni) in the water, sediment and benthic macroinvertebrates samples were investigated in a sub-basin in the southeast of Brazil in the city of São Carlos, São Paulo state, with the aim of verifying the metals and environment interaction with benthic communities regarding bioaccumulation. Hypothetically, there can be contamination by metals in the aquatic environment in the city due to lack of industrial effluent treatment. All samples were analysed by the USEPA adapted method and processed in an atomic absorption spectrophotometer. The sub-basin studied is contaminated by toxic metals in superficial water, sediment and benthic macroinvertebrates. The Bioaccumulation Factor showed a tendency for metal bioaccumulation by the benthic organisms for almost all the metal species. The results show a potential human and ecosystem health risk, contributing to metal contamination studies in aquatic environments in urban areas

Metal contamination in benthic macroinvertebrates in a sub-basin in the southeast of Brazil

Benthic macroinvertebrates have many useful properties that make possible the use of these organisms as sentinel in biomonitoring programmes in freshwater. Combined with the characteristics of the water and sediment, benthic macroinvertebrates are potential indicators of environmental quality. Thus, the spatial occurrence of potentially toxic metals (Al, Zn, Cr, Co, Cu, Fe, Mn and Ni) in the water, sediment and benthic macroinvertebrates samples were investigated in a sub-basin in the southeast of Brazil in the city of São Carlos, São Paulo state, with the aim of verifying the metals and environment interaction with benthic communities regarding bioaccumulation. Hypothetically, there can be contamination by metals in the aquatic environment in the city due to lack of industrial effluent treatment. All samples were analysed by the USEPA adapted method and processed in an atomic absorption spectrophotometer. The sub-basin studied is contaminated by toxic metals in superficial water, sediment and benthic macroinvertebrates. The Bioaccumulation Factor showed a tendency for metal bioaccumulation by the benthic organisms for almost all the metal species. The results show a potential human and ecosystem health risk, contributing to metal contamination studies in aquatic environments in urban areas

Seasonal study of contamination by metal in water and sediment in a sub-basin in the southeast of Brazil

The spatial and temporal occurrence of heavy metals (Al, Cd, Pb, Zn, Cr, Co, Cu, Fe, Mn and Ni) in water and sediment samples was investigated in a sub-basin in the southeast of Brazil (São Carlos, SP). All samples were analysed using the USEPA adapted metal method and processed in an atomic absorption spectrophotometer. The discriminant analysis demonstrated that there are significant seasonal differences of metal distribution in the water data, but there are no differences to sediment. The basin studied has high levels of contamination by toxic metals in superficial water and sediment. The superficial water, in the rainy season, presented high levels of Cr, Ni, Pb and Cd, while in the dry season it presented high levels of Zn and Ni. The Principal Component Analysis demonstrated that the season has a huge influence on the levels, types and distribution of metals found in water. The source of contamination was probably diffuse, due to products such as batteries and fluorescent lamps, whose dump discharge can contaminate the bodies of water in the region in the rainy season. Due to fires from the harvest of sugar cane, high levels of Zn were found into the environment, in the dry season

Cold fronts and reservoir limnology: an integrated approach towards the ecological dynamics of freshwater ecosystems

In this paper the authors discuss the effects of cold fronts on the dynamics of freshwater ecosystems of southeast South America. Cold fronts originating from the Antarctic show a monthly frequency that promotes turbulence and vertical mixing in reservoirs with a consequence to homogenize nutrient distribution, dissolved oxygen and temperature. Weak thermoclines and the athelomixis process immediately before, during and after the passage of cold fronts interfere with phytoplankton succession in reservoirs. Cyanobacteria blooms in eutrophic reservoirs are frequently connected with periods of stratification and stability of the water column. Cold fronts in the Amazon and Pantanal lakes may produce fish killings during the process of "friagem" associated mixing events. Further studies will try to implement a model to predict the impact of cold fronts and prepare management procedures in order to cope with cyanobacteria blooms during warm and stable water column periods. Changes in water quality of reservoirs are expected during circulation periods caused by cold fronts