Balanço hídrico da Bacia do Alto Paraguai por meio de dados TRMM e MOD16A2.

O armazenamento de água de uma bacia de drenagem determina sua segurança hídrica. A quantidade de água retida na bacia pode ser medida por meio do cálculo do balanço hídrico, definido pela entrada de água subtraída das saídas. As medidas de entrada e saída hídrica em uma bacia de drenagem são onerosas, o que torna o uso de dados de sensoriamento remoto uma ferramenta de grande impacto socioeconômico para este fim. Somado a isto, tem-se que estudos de disponibilidade hídrica com sensores orbitais são relativamente escassos para a Bacia do Alto Paraguai (BAP). Dessa forma, a partir do processamento de dados de precipitação do Tropical Rainfall Measuring Mission (TRMM) e de evapotranspiração do MODIS Global Evapotranspiration Project (MOD16), o presente trabalho traz uma estimativa do balanço hídrico da BAP com sensores orbitais. Para tanto, foi criada no ArcGIS 10 uma ferramenta no ModelBuilder. Os resultados indicam que a BAP possui um superávit hídrico anual entre 2000 e 2014, muito embora os parâmetros hídricos anuais sejam pouco correlacionados. No entanto, pode haver fenômenos atmosféricos-climáticos que maximizam a correlação entre os parâmetros hidrológicos e a anomalia de temperatura com atrasos de 2 a 5 anos, teleconexões defasadas com QBO e ENSO

Morphodynamics in the confluence of large regulated rivers: the case of Paraná and Paranapanema Rivers

The confluence of the Paraná and Paranapanema Rivers is studied according to morphology and dynamics. It is probably the only example of this type of fluvial environment involving a large, tropical and intensive regulated river. Confluence channels were monitored along a hydrological cycle (high-low water level) in terms of morphology, flow velocity, magnitude, structure, and bedload dynamics. In this case, hydrology is controlled by the flow of the tributary, which develops a continuous and well-defined thalweg since the collector channel (a secondary channel of the Paraná River) that presents relatively large bedforms that reduce stream power by increasing roughness. Although significant differences in channel morphology were not observed along the hydrological year, bed material texture indicates that the channel bottom is suffering a slight armoring process. This is probably the reason for the large asymmetry of channel confluence where the depth of the tributary channel is larger than that of the main collector channel (the Paraná left branch). The Rosana Dam, closed in 1987 and located 26 km upstream from the confluence, is the cause of the changes in sediment transport and the generation of the channel pavement. With the closing of the Porto Primavera Dam (2000) in the Paraná River (27 km upstream from the confluence) a new morphodynamics is foreseen for this environment, and this paper can be seen a relevant pioneer reference for environmental monitoring and management

Sponge spicule and phytolith evidence for Late Quaternary environmental changes in the tropical Pantanal wetlands of western Brazil.

The environmental history of the central Pantanal wetlands of western Brazil is inferred for the last 19 kyrs based on a multi-indicator paleolimnological analysis of a sediment core from Lake Negra. The core, dated by 14C and OSL, shows variations in the abundance, diversity, and preservation of sponge spicules and phytoliths through time, consistent with changing aquatic environments. In the late Pleistocene, Lake Negra was influenced by a strong monsoon and fluvial depositional processes, whereas in the Holocene, there was a drier interval where the lake was more isolated on the floodplain. Hiatuses in the stratigraphy resulted from both wet and dry conditions, through fluvial channel scour or subaerial exposure of the lake floor, respectively. Data suggest that floodplain lakes in the Pantanal wetlands and similar riverine wetlands respond in a complex and, at times, indirect manner to climate change, and the dynamics of the adjacent fluvial system must be accounted for when interpreting paleohydrology and vegetation patterns

Inhibition of Hedgehog Signaling Decreases Proliferation and Clonogenicity of Human Mesenchymal Stem Cells

Human mesenchymal stem cells (hMSC) have the ability to differentiate into osteoblasts, adipocytes and chondrocytes. We have previously shown that hMSC were endowed with a basal level of Hedgehog signaling that decreased after differentiation of these cells. Since hMSC differentiation is associated with growth-arrest we investigated the function of Hh signaling on cell proliferation. Here, we show that inhibition of Hh signaling, using the classical inhibitor cyclopamine, or a siRNA directed against Gli-2, leads to a decrease in hMSC proliferation. This phenomenon is not linked to apoptosis but to a block of the cells in the G0/G1 phases of the cell cycle. At the molecular level, it is associated with an increase in the active form of pRB, and a decrease in cyclin A expression and MAP kinase phosphorylation. Inhibition of Hh signaling is also associated with a decrease in the ability of the cells to form clones. By contrast, inhibition of Hh signaling during hMSC proliferation does not affect their ability to differentiate. This study demonstrates that hMSC are endowed with a basal Hedgehog signaling activity that is necessary for efficient proliferation and clonogenicity of hMSC. This observation unravels an unexpected new function for Hedgehog signaling in the regulation of human mesenchymal stem cells and highlights the critical function of this morphogen in hMSC biology

Self-Renewal of Acute Lymphocytic Leukemia Cells Is Limited by the Hedgehog Pathway Inhibitors Cyclopamine and IPI-926

Conserved embryonic signaling pathways such as Hedgehog (Hh), Wingless and Notch have been implicated in the pathogenesis of several malignancies. Recent data suggests that Hh signaling plays a role in normal B-cell development, and we hypothesized that Hh signaling may be important in precursor B-cell acute lymphocytic leukemia (B-ALL). We found that the expression of Hh pathway components was common in human B-ALL cell lines and clinical samples. Moreover, pathway activity could be modulated by Hh ligand or several pathway inhibitors including cyclopamine and the novel SMOOTHENED (SMO) inhibitor IPI-926. The inhibition of pathway activity primarily impacted highly clonogenic B-ALL cells expressing aldehyde dehydrogenase (ALDH) by limiting their self-renewal potential both in vitro and in vivo. These data demonstrate that Hh pathway activation is common in B-ALL and represents a novel therapeutic target regulating self-renewal and persistence of the malignant clone

Coordinated Regulation of Intestinal Functions in C. elegans by LIN-35/Rb and SLR-2

LIN-35 is the sole C. elegans representative of the pocket protein family, which includes the mammalian Retinoblastoma protein pRb and its paralogs p107 and p130. In addition to having a well-established and central role in cell cycle regulation, pocket proteins have been increasingly implicated in the control of critical and diverse developmental and cellular processes. To gain a greater understanding of the roles of pocket proteins during development, we have characterized a synthetic genetic interaction between lin-35 and slr-2, which we show encodes a C2H2-type Zn-finger protein. Whereas animals harboring single mutations in lin-35 or slr-2 are viable and fertile, lin-35; slr-2 double mutants arrest uniformly in early larval development without obvious morphological defects. Using a combination of approaches including transcriptome profiling, mosaic analysis, starvation assays, and expression analysis, we demonstrate that both LIN-35 and SLR-2 act in the intestine to regulate the expression of many genes required for normal nutrient utilization. These findings represent a novel role for pRb family members in the maintenance of organ function. Our studies also shed light on the mechanistic basis of genetic redundancy among transcriptional regulators and suggest that synthetic interactions may result from the synergistic misregulation of one or more common targets

Inactivation of TIF1γ Cooperates with KrasG12D to Induce Cystic Tumors of the Pancreas

Inactivation of the Transforming Growth Factor Beta (TGFβ) tumor suppressor pathway contributes to the progression of Pancreatic Ductal AdenoCarcinoma (PDAC) since it is inactivated in virtually all cases of this malignancy. Genetic lesions inactivating this pathway contribute to pancreatic tumor progression in mouse models. Transcriptional Intermediary Factor 1 gamma (TIF1γ) has recently been proposed to be involved in TGFβ signaling, functioning as either a positive or negative regulator of the pathway. Here, we addressed the role of TIF1γ in pancreatic carcinogenesis. Using conditional Tif1γ knockout mice (Tif1γlox/lox), we selectively abrogated Tif1γ expression in the pancreas of Pdx1-Cre;Tif1γlox/lox mice. We also generated Pdx1-Cre;LSL-KrasG12D;Tif1γlox/lox mice to address the effect of Tif1γ loss-of-function in precancerous lesions induced by oncogenic KrasG12D. Finally, we analyzed TIF1γ expression in human pancreatic tumors. In our mouse model, we showed that Tif1γ was dispensable for normal pancreatic development but cooperated with Kras activation to induce pancreatic tumors reminiscent of human Intraductal Papillary Mucinous Neoplasms (IPMNs). Interestingly, these cystic lesions resemble those observed in Pdx1-Cre;LSL-KrasG12D;Smad4lox/lox mice described by others. However, distinctive characteristics, such as the systematic presence of endocrine pseudo-islets within the papillary projections, suggest that SMAD4 and TIF1γ don't have strictly redundant functions. Finally, we report that TIF1γ expression is markedly down-regulated in human pancreatic tumors by quantitative RT–PCR and immunohistochemistry supporting the relevance of these findings to human malignancy. This study suggests that TIF1γ is critical for tumor suppression in the pancreas, brings new insight into the genetics of pancreatic cancer, and constitutes a promising model to decipher the respective roles of SMAD4 and TIF1γ in the multifaceted functions of TGFβ in carcinogenesis and development

MicroRNAs MiR-17, MiR-20a, and MiR-106b Act in Concert to Modulate E2F Activity on Cell Cycle Arrest during Neuronal Lineage Differentiation of USSC

MicroRNAs are short (∼22 nt) non-coding regulatory RNAs that control gene expression at the post-transcriptional level. Here the functional impact of microRNAs on cell cycle arrest during neuronal lineage differentiation of unrestricted somatic stem cells from human cord blood (USSC) was analyzed./M transition. Most strikingly, miR-17, -20a, and -106b were found to promote cell proliferation by increasing the intracellular activity of E2F transcription factors, despite the fact that miR-17, -20a, and -106b directly target the transcripts that encode for this protein family./S transition

Identification of RegIV as a Novel GLI1 Target Gene in Human Pancreatic Cancer

GLI1 is the key transcriptional factor in the Hedgehog signaling pathway in pancreatic cancer. RegIV is associated with regeneration, and cell growth, survival, adhesion and resistance to apoptosis. We aimed to study RegIV expression in pancreatic cancer and its relationship to GLI1.GLI1 and RegIV expression were evaluated in tumor tissue and adjacent normal tissues of pancreatic cancer patients and 5 pancreatic cancer cell lines by qRT-PCR, Western blot, and immunohistochemistry (IHC), and the correlation between them. The GLI1-shRNA lentiviral vector was constructed and transfected into PANC-1, and lentiviral vector containing the GLI1 expression sequence was constructed and transfected into BxPC-3. GLI1 and RegIV expression were evaluated by qRT-PCR and Western blot. Finally we demonstrated RegIV to be the target of GLI1 by chromatin immunoprecipitation (CHIP) and electrophoretic mobility shift assays (EMSA).The results of IHC and qRT-PCR showed that RegIV and GLI1 expression was higher in pancreatic cancer tissues versus adjacent normal tissues (p<0.001). RegIV expression correlated with GLI1 expression in these tissues (R = 0.795, p<0.0001). These results were verified for protein (R = 0.939, p = 0.018) and mRNA expression (R = 0.959, p = 0.011) in 5 pancreatic cancer cell lines. RegIV mRNA and protein expression was decreased (94.7±0.3%, 84.1±0.5%; respectively) when GLI1 was knocked down (82.1±3.2%, 76.7±2.2%; respectively) by the RNAi technique. GLI1 overexpression in mRNA and protein level (924.5±5.3%, 362.1±3.5%; respectively) induced RegIV overexpression (729.1±4.3%, 339.0±3.7%; respectively). Moreover, CHIP and EMSA assays showed GLI1 protein bound to RegIV promotor regions (GATCATCCA) in pancreatic cancer cells.GLI1 promotes RegIV transcription by binding to the RegIV gene promoter in pancreatic cancer

CREB Inhibits AP-2α Expression to Regulate the Malignant Phenotype of Melanoma

The loss of AP-2alpha and increased activity of cAMP-responsive element binding (CREB) protein are two hallmarks of malignant progression of cutaneous melanoma. However, the molecular mechanism responsible for the loss of AP-2alpha during melanoma progression remains unknown.Herein, we demonstrate that both inhibition of PKA-dependent CREB phosphorylation, as well as silencing of CREB expression by shRNA, restored AP-2alpha protein expression in two metastatic melanoma cell lines. Moreover, rescue of CREB expression in CREB-silenced cell lines downregulates expression of AP-2alpha. Loss of AP-2alpha expression in metastatic melanoma occurs via a dual mechanism involving binding of CREB to the AP-2alpha promoter and CREB-induced overexpression of another oncogenic transcription factor, E2F-1. Upregulation of AP-2alpha expression following CREB silencing increases endogenous p21(Waf1) and decreases MCAM/MUC18, both known to be downstream target genes of AP-2alpha involved in melanoma progression.Since AP-2alpha regulates several genes associated with the metastatic potential of melanoma including c-KIT, VEGF, PAR-1, MCAM/MUC18, and p21(Waf1), our data identified CREB as a major regulator of the malignant melanoma phenotype