Cyclo(His-Pro) up-regulates heme oxygenase 1 via activation of Nrf2-ARE signalling

Paraquat (1,1'-dimethyl-4,4'-bipyridinium), a widely used non-selective herbicide, is a redox cycling agent with adverse effects on dopamine systems. Epidemiological data have shown that exposure to paraquat is one of the several risk factors for Parkinson's disease. We have already shown that cyclo(His-Pro), an endogenous cyclic dipeptide produced by the cleavage of the thyrotropin releasing hormone, has a cytoprotective effect through a mechanism involving Nrf2 activation that decreases production of reactive oxygen species and increases glutathione synthesis. Using primary neuronal cultures and PC12 cells as targets of paraquat neurotoxicity, we addressed whether and how cyclo(His-Pro) causes cellular protective response against paraquat-mediated cell death. We found that cyclo(His-Pro) attenuated reactive oxygen species production, and prevented glutathione depletion by up-regulating Nrf2 gene expression, triggering its nuclear accumulation and activating the expression of heme oxygenase1. These protective effects were abolished by RNA interference-mediated Nrf2 knock down whereas were unaffected by RNA interference-mediated Keap1 knock down. Inhibition of heme oxygenase activity decreased cyclo(His-Pro)-induced neuroprotection. These results suggest that cyclo(His-Pro), acting as a selective activator of the brain modulable Nrf2 pathway, may be a promising candidate as neuroprotective agent that act through induction of phase II genes.     

Preventive and Curative Biological Treatments for Control of Botrytis cinerea Stem Canker of Greenhouse Tomatoes

The effects of biological treatments with PlantShield^®, Prestop^®, Quadra 136, RootShield^®, and S33 (Rhodosporidium diobovatum) and chemical treatment with Decree^® applied as a preventive or curative sprays on stem canker caused by Botrytis cinerea on tomato plants grown in sawdust were studied under near-commercial greenhouse conditions. Prestop^® and Decree^®, applied as preventive or curative sprays, PlantShield^® applied as curative spray, and S33 and Q-136 applied as preventive or preventive plus one spray to wounded surface provided season-long protection from B. cinerea stem canker. These treatments also increased fruit yield and decreased the number of dead plants compared with the inoculated control.     

Morphological diversity of leaves of <Emphasis Type="Italic">Pseudoprotophyllum</Emphasis> (Platanaceae) from the Turonian-Coniacian of the northern coast of the Sea of Okhotsk

Fossil plants of the Chingandzha flora were studied from volcanogenic sediments of the Chingandzha and Rond formations on the northern coast of the Sea of Okhotsk. It was concluded that all platanaceous leaves earlier described in this flora as different taxa belong to one highly variable species, Pseudoprotophyllum cordatum Samyl. emend. Shczepetov et Golovneva.     

Late Glacial and Holocene environmental and climatic changes from a limnological transect through Colombia, northern South America

We present a synthesis of the palaeolimnological and palaeoclimatic reconstructions of four sites in Colombia. The record from Lake El Caimito, the westernmost site on the Pacific Coast, dates from the Late Holocene and shows lacustrine sedimentation frequently interrupted by fluvial pulses. These pulses probably reflect periods of increased precipitation related to La Niña phases. East of El Caimito site is the Patía swamp, situated between the Western and Central Andean Cordilleras. The Patía records the dynamics of forest expansion/reduction and changes in water levels. Although the climatic signal of the Patia core is difficult to reconstruct, there is a clear increase in humidity in the Mid-Holocene. The Fúquene Lake record, on the Eastern Andean Cordillera, records dry and cold conditions during the Late Pleistocene, very humid conditions for the early Mid-Holocene, and dry conditions during the mid-Late Holocene. Las Margaritas site, on the eastern savannas, records dry conditions during the Early Holocene and overall humid conditions for the Mid- and Late Holocene. Climate conditions from the Fuquene and Las Margaritas sites seem to reflect the Holocene movements of the Intertropical Convergence Zone (ITCZ); the latter site being more affected by humidity coming from the Amazon region.     

Phylogeography of the cactophilic species Drosophila gouveai: demographic events and divergence timing in dry vegetation enclaves in eastern Brazil

Aim  The aim of this study was to assess the causal mechanisms underlying populational subdivision in Drosophila gouveai , a cactophilic species associated with xeric vegetation enclaves in eastern Brazil. A secondary aim was to investigate the genetic effects of Pleistocene climatic fluctuations on these environments.
Location  Dry vegetation enclaves within the limits of the Cerrado domain in eastern Brazil.
Methods  We determined the mitochondrial DNA haplotypes of 55 individuals (representing 12 populations) based on sequence data of a 483-bp fragment from the cytochrome c oxidase subunit II (COII) gene. Phylogenetic and coalescent analyses were used to test for the occurrence of demographic events and to infer the time of divergence amongst genetically independent groups.
Results  Our analyses revealed the existence of two divergent subclades (G1 and G2) plus an introgressed clade restricted to the southernmost range of D. gouveai . Subclades G1 and G2 displayed genetic footprints of range expansion and segregated geographical distributions in south-eastern and some central highland regions, east and west of the Paraná River valley. Molecular dating indicated that the main demographic and diversification events occurred in the late to middle Pleistocene.
Main conclusions  The phylogeographical and genetic patterns observed for D. gouveai in this study are consistent with changes in the distribution of dry vegetation in eastern Brazil. All of the estimates obtained by molecular dating indicate that range expansion and isolation pre-dated the Last Glacial Maximum, occurring during the late to middle Pleistocene, and were probably triggered by climatic changes during the Pleistocene. The current patchy geographical distribution and population subdivision in D. gouveai is apparently closely linked to these past events.     

Degradation of proteins within the endoplasmic reticulum.

Certain newly synthesized proteins within the endoplasmic reticulum undergo rapid turnover by a non-lysosomal proteolytic pathway. Biochemical and morphological evidence has suggested that these proteins never leave the endoplasmic reticulum before they are degraded. The mechanism(s) for the selective targeting of proteins for degradation within the endoplasmic reticulum is still not understood, but appears to rely on specific structural determinants on the protein substrates. Important cellular functions are likely to be served by this endoplasmic reticulum degradative system, including disposal of abnormal proteins and the selective turnover of metabolically regulated proteins.     

Does vinblastine add to the potency of alpha interferon in the treatment of renal cell carcinoma?

The combination of alpha interferon and vinblastine has been reported to yield a response rate of 30-40% in previously untreated patients with metastatic renal cell carcinoma. This combination was given to nine patients with advanced metastatic renal carcinoma after they failed or relapsed on alpha-interferon alone, to attempt to evaluate the role of vinblastine in this combination. Neither complete nor partial response was observed. Two patients had disease stabilization for two and seven months. Our preliminary results suggest that vinblastine did not add to the efficacy of interferon in this group of patients.     

Inactivation and oxidative modification of Cu,Zn superoxide dismutase by stimulated neutrophils: the appearance of new catalytically active structures.

Bovine superoxide dismutase (SOD) was inactivated during incubation with phorbol myristate acetate-stimulated neutrophils. In addition, stimulated neutrophils were able to disrupt the SOD structure. Inactivation and structural damage were dependent on the action of hypochlorous acid, an oxidant generated by the myeloperoxidase-hydrogen peroxide-chloride system of neutrophils. Incubation of SOD with stimulated neutrophils lead to long-wavelength fluorescence (ex, 350 nm; em, 450 nm) and the appearance of new structural forms with other isoelectric points. These additional forms possess catalytic activity. Generation of catalytically active new forms of SOD demonstrates the inaccessibility of the active centre of SOD to hypochlorite and may be a reason for the successful application of SOD during anti-inflammatory therapy.