KeaA, a Dictyostelium kelch-domain protein that regulates the response to stress and development

<p>Abstract</p> <p>Background</p> <p>The protein kinase YakA is responsible for the growth arrest and induction of developmental processes that occur upon starvation of <it>Dictyostelium </it>cells. <it>yakA^-</it>cells are aggregation deficient, have a faster cell cycle and are hypersensitive to oxidative and nitrosoative stress. With the aim of isolating members of the YakA pathway, suppressors of the death induced by nitrosoative stress in the <it>yakA^-</it>cells were identified. One of the suppressor mutations occurred in <it>keaA</it>, a gene identical to DG1106 and similar to Keap1 from mice and the Kelch protein from Drosophila, among others that contain Kelch domains.</p> <p>Results</p> <p>A mutation in <it>keaA </it>suppresses the hypersensitivity to oxidative and nitrosoative stresses but not the faster growth phenotype of <it>yakA^-</it>cells. The growth profile of <it>keaA </it>deficient cells indicates that this gene is necessary for growth. <it>keaA </it>deficient cells are more resistant to nitrosoative and oxidative stress and <it>keaA </it>is necessary for the production and detection of cAMP. A morphological analysis of <it>keaA </it>deficient cells during multicellular development indicated that, although the mutant is not absolutely deficient in aggregation, cells do not efficiently participate in the process. Gene expression analysis using cDNA microarrays of wild-type and <it>keaA </it>deficient cells indicated a role for KeaA in the regulation of the cell cycle and pre-starvation responses.</p> <p>Conclusions</p> <p>KeaA is required for cAMP signaling following stress. Our studies indicate a role for kelch proteins in the signaling that regulates the cell cycle and development in response to changes in the environmental conditions.</p

c-Src inhibition improves cardiovascular function but not remodeling or fibrosis in Ang II-induced hypertension

c-Src plays an important role in angiotensin II (Ang II) signaling. Whether this member of the Src family kinases is involved in the development of Ang II–induced hypertension and associated cardiovascular damage in vivo remains unknown. Here, we studied Ang II–infused (400 ng/kg/min) mice in which c-Src was partially deleted (c-Src+/−) and in wild-type (WT, c-Src+/+) mice treated with a c-Src inhibitor (CGP077675; 25 mg/kg/d). Ang II increased blood pressure and induced endothelial dysfunction in WT mice, responses that were ameliorated in c-Src+/− and CGP077675-treated mice. Vascular wall thickness and cross-sectional area were similarly increased by Ang II in WT and c-Src+/− mice. CGP077675 further increased cross-sectional area in hypertensive mice. Cardiac dysfunction (ejection fraction and fractional shortening) in Ang II–infused WT mice was normalized in c-Src+/− mice. Increased oxidative stress (plasma thiobarbituric acid–reactive substances, hydrogen peroxide, and vascular superoxide generation) in Ang II–infused WT mice was attenuated in c-Src–deficient and CGP077675-treated mice. Hyperactivation of vascular c-Src, ERK1/2 (extracellular signal–regulated kinase 1/2), and JNK (c-Jun N-terminal kinase) in hypertensive mice was normalized in CGP077675-treated and c-Src+/− mice. Vascular fibronectin was increased by Ang II in all groups and further augmented by CGP077675. Cardiac fibrosis and inflammation induced by Ang II were amplified in c-Src+/− and CGP-treated mice. Our data indicate that although c-Src downregulation attenuates development of hypertension, improves endothelial and cardiac function, reduces oxidative stress, and normalizes vascular signaling, it has little beneficial effect on fibrosis. These findings suggest a divergent role for c-Src in Ang II–dependent hypertension, where c-Src may be more important in regulating redox-sensitive cardiac and vascular function than fibrosis and remodeling

Differential renal effects of candesartan at high-and ultra-high doses in diabetic mice: potential role of ACE2/AT2R/Mas

High doses of Ang II receptor (AT1R) blockers (ARBs) are renoprotective in diabetes. Underlying mechanisms remain unclear. We evaluated whether high/ultra-high doses of candesartan (ARB) up-regulate angiotensin-converting enzyme 2 (ACE2)/Ang II type 2 receptor (AT2R)/Mas receptor [protective axis of the of the renin–angiotensin system (RAS)] in diabetic mice. Systolic blood pressure (SBP), albuminuria and expression/activity of RAS components were assessed in diabetic db/db and control db/+ mice treated with increasing candesartan doses (intermediate, 1 mg/kg/d; high, 5 mg/kg/d; ultra-high, 25 and 75 mg/kg/d; 4 weeks). Lower doses candesartan did not influence SBP, but ultra-high doses reduced SBP in both groups. Plasma glucose and albuminuria were increased in db/db compared with db/+ mice. In diabetic mice treated with intermediate dose candesartan, renal tubular damage and albuminuria were ameliorated and expression of ACE2, AT2R and Mas and activity of ACE2 were increased, effects associated with reduced ERK1/2 phosphorylation, decreased fibrosis and renal protection. Ultra-high doses did not influence the ACE2/AT2R/Mas axis and promoted renal injury with increased renal ERK1/2 activation and exaggerated fibronectin expression in db/db mice. Our study demonstrates dose-related effects of candesartan in diabetic nephropathy: intermediate–high dose candesartan is renoprotective, whereas ultra-high dose candesartan induces renal damage. Molecular processes associated with these effects involve differential modulation of the ACE2/AT2R/Mas axis: intermediate–high dose candesartan up-regulating RAS protective components and attenuating pro-fibrotic processes, and ultra-high doses having opposite effects. These findings suggest novel mechanisms through the protective RAS axis, whereby candesartan may ameliorate diabetic nephropathy. Our findings also highlight potential injurious renal effects of ultra-high dose candesartan in diabetes

Redes Organizacionais e Desenvolvimento Territorial

Delving into the subject of intangible assets, this paper brings to the analytical fore of regional studies, the concept of Relational Capital. It further shows why this particular asset is as important to growth and development of a given region, as the conventional productive resources brought forward in the traditional literature. The theoretical construct presented is supported by extensive empirical evidence, springing from field research. The adopted methodology led to the construction of a set of indicators of relational nature. These, in turn, enabled the checks and measurements of certain dimensions relevant to the facts of interest, as such, opening up new trends in comparative studies at both the inter and the intra-regional levels.O presente artigo traz para as análises regionais a temática dos ativos intangíveis, introduzindo o conceito de Capital Relacional. Mostra porque este recurso é tão importante para o crescimento e desenvolvimento de uma dada região, quanto os demais recursos produtivos, tradicionalmente citados na literatura. A concepção teórica apresentada foi enriquecida com evidências empíricas, advindas de uma pesquisa de campo. A metodologia então adotada permitiu a criação de um conjunto de indicadores, de natureza relacional, que tornou possível a aferição e a mensuração de dimensões relevantes do fenômeno de interesse, abrindo perspectivas para novas pesquisas comparativas, a nível inter ou intra-regiona

Spring phytoplankton communities of the Labrador Sea (2005–2014): pigment signatures, photophysiology and elemental ratios

The Labrador Sea is an ideal region to study the biogeographical, physiological, and biogeochemical implications of phytoplankton community composition due to sharp transitions between distinct water masses across its shelves and central basin. We have investigated the multi-year (2005–2014) distributions of late spring and early summer (May to June) phytoplankton communities in the various hydrographic settings of the Labrador Sea. Our analysis is based on pigment markers (using CHEMTAX analysis), and photophysiological and biogeochemical characteristics associated with each phytoplankton community. Diatoms were the most abundant group, blooming first in shallow mixed layers of haline-stratified Arctic shelf waters. Along with diatoms, chlorophytes co-dominated at the western end of the section (particularly in the polar waters of the Labrador Current (LC)), whilst Phaeocystis co-dominated in the east (modified polar waters of the West Greenland Current (WGC)). Pre-bloom conditions occurred in deeper mixed layers of the central Labrador Sea in May, where a mixed assemblage of flagellates (dinoflagellates, prasinophytes, prymnesiophytes, particularly coccolithophores, and chrysophytes/pelagophytes) occurred in low-chlorophyll areas, succeeding to blooms of diatoms and dinoflagellates in thermally stratified Atlantic waters in June. Light-saturated photosynthetic rates and saturation irradiance levels were highest at stations where diatoms were the dominant phytoplankton group ( >  70 % of total chlorophyll a), as opposed to stations where flagellates were more abundant (from 40 up to 70 % of total chlorophyll a). Phytoplankton communities from the WGC (Phaeocystis and diatoms) had lower light-limited photosynthetic rates, with little evidence of photoinhibition, indicating greater tolerance to a high light environment. By contrast, communities from the central Labrador Sea (dinoflagellates and diatoms), which bloomed later in the season (June), appeared to be more sensitive to high light levels. Ratios of accessory pigments (AP) to total chlorophyll a (TChl a) varied according to phytoplankton community composition, with polar phytoplankton (cold-water related) having lower AP  :  TChl a. Polar waters (LC and WGC) also had higher and more variable particulate organic carbon (POC) to particulate organic nitrogen (PON) ratios, suggesting the influence of detritus from freshwater input, derived from riverine, glacial, and/or sea ice meltwater. Long-term observational shifts in phytoplankton communities were not assessed in this study due to the short temporal frame (May to June) of the data. Nevertheless, these results add to our current understanding of phytoplankton group distribution, as well as an evaluation of the biogeochemical role (in terms of C  :  N ratios) of spring phytoplankton communities in the Labrador Sea, which will assist our understanding of potential long-term responses of phytoplankton communities in high-latitude oceans to a changing climate

Biogeographical patterns and environmental controls of phytoplankton communities from contrasting hydrographical zones of the Labrador Sea

The Labrador Sea is an important oceanic sink for atmospheric CO2 because of intensive convective mixing during winter and extensive phytoplankton blooms that occur during spring and summer. Therefore, a broad-scale investigation of the responses of phytoplankton community composition to environmental forcing is essential for understanding planktonic food-web organisation and biogeochemical functioning in the Labrador Sea. Here, we investigated the phytoplankton community structure (>4 μm) from near surface blooms (1.2 mg chla m−3) occurred on and near the shelves in May and in offshore waters of the central Labrador Sea in June due to haline- and thermal-stratification, respectively. Sea ice-related (Fragilariopsis cylindrus and F. oceanica) and Arctic diatoms (Fossula arctica, Bacterosira bathyomphala and Thalassiosira hyalina) dominated the relatively cold (<0 °C) and fresh (salinity < 33) waters over the Labrador shelf (e.g., on the southwestern side of the Labrador Sea), where sea-ice melt and Arctic outflow predominates. On the northeastern side of the Labrador Sea, intense blooms of the colonial prymnesiophyte Phaeocystis pouchetii and diatoms, such as Thalassiosira nordenskioeldii, Pseudo-nitzschia granii and Chaetoceros socialis, occurred in the lower nutrient waters (nitrate < 3.6 μM) of the West Greenland Current. The central Labrador Sea bloom occurred later in the season (June) and was dominated by Atlantic diatoms, such as Ephemera planamembranacea and Fragilariopsis atlantica. The data presented here demonstrate that the Labrador Sea spring and early summer blooms are composed of contrasting phytoplankton communities, for which taxonomic segregation appears to be controlled by the physical and biogeochemical characteristics of the dominant water masses

Ethylene-induced Transcriptional And Hormonal Responses At The Onset Of Sugarcane Ripening

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The effects of ethephon as a sugarcane ripener are attributed to ethylene. However, the role of this phytohormone at the molecular level is unknown. We performed a transcriptome analysis combined with the evaluation of sucrose metabolism and hormone profiling of sugarcane plants sprayed with ethephon or aminoethoxyvinylglycine (AVG), an ethylene inhibitor, at the onset of ripening. The differential response between ethephon and AVG on sucrose level and sucrose synthase activity in internodes indicates ethylene as a potential regulator of sink strength. The correlation between hormone levels and transcriptional changes suggests ethylene as a trigger of multiple hormone signal cascades, with approximately 18% of differentially expressed genes involved in hormone biosynthesis, metabolism, signalling, and response. A defence response elicited in leaves favoured salicylic acid over the ethylene/jasmonic acid pathway, while the upper internode was prone to respond to ethylene with strong stimuli on ethylene biosynthesis and signalling genes. Besides, ethylene acted synergistically with abscisic acid, another ripening factor, and antagonistically with gibberellin and auxin. We identified potential ethylene target genes and characterized the hormonal status during ripening, providing insights into the action of ethylene at the site of sucrose accumulation. A molecular model of ethylene interplay with other hormones is proposed.7Sao Paulo Research Foundation (FAPESP) [2008/52146-0, 2008/57495-3, 2013/15576-5, 2012/13920-8, 2008/54201-9]National Council for Scientific and Technological Development (CNPq) [140767/2012-6, 160132/2011-3]ECMGMSMMRVRCNPqNational Science Foundation [DBI-0521250]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

A Novel Stress-induced Sugarcane Gene Confers Tolerance To Drought, Salt And Oxidative Stress In Transgenic Tobacco Plants.

Drought is a major abiotic stress that affects crop productivity worldwide. Sugarcane can withstand periods of water scarcity during the final stage of culm maturation, during which sucrose accumulation occurs. Meanwhile, prolonged periods of drought can cause severe plant losses. In a previous study, we evaluated the transcriptome of drought-stressed plants to better understand sugarcane responses to drought. Among the up-regulated genes was Scdr1 (sugarcane drought-responsive 1). The aim of the research reported here was to characterize this gene. Scdr1 encodes a putative protein containing 248 amino acids with a large number of proline (19%) and cysteine (13%) residues. Phylogenetic analysis showed that ScDR1is in a clade with homologs from other monocotyledonous plants, separate from those of dicotyledonous plants. The expression of Scdr1 in different varieties of sugarcane plants has not shown a clear association with drought tolerance. The overexpression of Scdr1 in transgenic tobacco plants increased their tolerance to drought, salinity and oxidative stress, as demonstrated by increased photosynthesis, water content, biomass, germination rate, chlorophyll content and reduced accumulation of ROS. Physiological parameters, such as transpiration rate (E), net photosynthesis (A), stomatal conductance (gs) and internal leaf CO(2) concentration, were less affected by abiotic stresses in transgenic Scdr1 plants compared with wild-type plants. Overall, our results indicated that Scdr1 conferred tolerance to multiple abiotic stresses, highlighting the potential of this gene for biotechnological applications.7e4469