Activation of human T lymphocytes via integrin signaling induced by RGD-disintegrins

Adhesive interactions play important roles in coordinating T cell migration and activation, which are mediated by binding of integrins to RGD motif found on extracellular matrix proteins. Disintegrins, isolated from snake venoms, contain the RGD sequence that confers selectivity to integrin interaction. We have investigated the ability of three RGD-disintegrins, ligands of alpha(5)beta(1) and alpha(v)beta(3), Flavoridin (Fl), Kistrin (Kr) and Echistatin (Ech), in modulating the activation of human T lymphocyte. The disintegrins induced T cell proliferation and CD69 expression. This activation parallels with actin cytoskeleton reorganization and tyrosine phosphorylation. Furthermore, the peptides induced focal adhesion kinase (FAK) and phosphoinositide 3-kinase (PI3K) activation. Finally, RGD-disintegrins were capable of driving NF-kappaB nuclear translocation and c-Fos expression, in a PI3K and ERK1/2 activities dependent manner. This report is the first to show that RGD-disintegrins interact with integrins on human T lymphocyte surface, modulating cell proliferation and activation of specific pathways coupled to integrin receptor.     

P2Z/P2X7 receptor-dependent apoptosis of dendritic cells

Macrophages andthymocytes expressP_2Z/P2X₇nucleotide receptors that bind extracellular ATP. These receptors playa role in immune development and control of microbial infections, but their presence on dendritic cells has not been reported. Weinvestigated whether extracellular ATP could triggerP_2Z/P2X₇receptor-dependent apoptosis of dendritic cells. Apoptosis could beselectively triggered by tetrabasic ATP, since otherpurine/pyrimidine nucleotides were ineffective, and it wasmimicked by the P_2Z receptoragonist, benzoylbenzoyl ATP, and blocked by magnesium and theirreversible antagonist, oxidized ATP. RT-PCR analysis confirmed themRNA expression of theP_2Z/P2X₇receptor and the absence of P2X₁.Caspase inhibitors and cycloheximide had only a partial effect on theapoptosis, suggesting that a caspase-independent mechanism may also beoperative. Brief treatment with ATP led to an increase in theintracellular calcium concentration and permeabilization of the plasmamembrane to Lucifer yellow, which diffused throughout the dendriticcell cytosol. Other small extracellular molecules may thus attain a similar intracellular distribution, perhaps activating endogenous proteases that contribute to initiation of apoptosis.     

Association of genetic variants rs641153 (CFB), rs2230199 (C3), and rs1410996 (CFH) with age-related macular degeneration in a Brazilian population

This study aimed to investigate the association among genetic variants of the complement pathway CFB R32Q (rs641153), C3 R102G (rs2230199), and CFH (rs1410996) with age-related macular degeneration (AMD) in a sample of the Brazilian population. In a case-control study, 484 AMD patients were classified according to the clinical age-related maculopathy grading system (CARMS) and compared to 479 unrelated controls. The genetic variants rs1410996 of complement H (CFH), rs641153 of complement factor B (CFB), and rs2230199 of complement 3 (C3) were evaluated through polymerase chain reaction (PCR) and direct sequencing. The associations between single nucleotide polymorphisms (SNPs) and AMD, adjusted by age, were assessed by using logistic regression models. A statistically significant association was observed between AMD risk and rs2230199 variant with an OR of 2.01 (P  = 0.0002) for CG individuals compared to CC individuals. Regarding the comparison of advanced AMD versus the control group, the OR was 2.12 (P = 0.0036) for GG versus AA genotypes for rs1410996 variant. Similarly, the OR for rs2230199 polymorphism was 2.3034 (P  = 5.47^e-05) when comparing CG individuals to CC carriers. In contrast, the rs641153 variant showed a significant protective effect against advanced AMD for GA versus GG genotype (OR = 0.4406; P  = 0.0019). When comparing wet AMD versus controls, a significant association was detected for rs1410996 variant (OR = 2.16; P  = 0.0039) comparing carriers of the homozygous GG versus AA genotype, as well as in the comparisons of GG (OR = 3.0713; P  = 0.0046) and CG genotypes (OR = 2.2249; P  = 0.0002) versus CC genotype for rs2230199 variant, respectively. The rs641153 variant granted a significant protective effect against wet AMD for GA versus GG genotypes (OR = 0.4601; P  = 0.0044). Our study confirmed the risk association between rs2230199 and rs1410996 variants and AMD, and the protective role against AMD for rs641153 variant.     

Evidence of osteomyelitis in the dentary of the late Triassic rhynchocephalian Clevosaurus brasiliensis (Lepidosauria: Rhynchocephalia) from southern Brazil and behavioural implications

Clevosaurus was a cosmopolitan Rhynchocephalia genus restricted to the Late Triassic and the Early Jurassic. In Brazil, C. brasiliensis is one of the most conspicuous species collected from the Candelária Sequence (Riograndia Assemblage Zone, Norian age) of the Santa Maria Supersequence. Several jaws of C. brasiliensis are housed in the Laboratório de Paleontologia de Vertebrados of the Instituto de Geociências-UFRGS. Some of these jaws bear a relatively small protuberant bony callus on the anterolateral margin of the dentary, evidenced by a different tissue pattern incorporating small pits and discrete grooves. This pattern closely resembles a common bone infection known in the mandible of the extant Sphenodon punctatus. Although this similarity, the infection may be the result of two possible processes: as consequence of orthal jaw shearing movements during feeding at the moments that the dentary impacts with the enlarged premaxillary tooth or due to injuries produced after fights between conspecific individuals (as is the case for S. punctatus). If the second hypothesis is correct, the same pathological processes probably occurred in the Late Triassic C. brasiliensis indicating that similar ethological conditions were already present at the beginning of the Mesozoic, during the initial radiation of the lepidosaurian clade.     

Changes in leaf gas exchange,chlorophyll a fluorescence and antioxidant metabolism within wheat leaves infected by Bipolaris sorokiniana

The photosynthetic performance (leaf gas exchange and chlorophyll a (Chla) fluorescence), activities of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), ascorbate peroxidase (APX)] and the concentrations of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA) in the flag leaves of plants from two wheat cultivars with contrasting levels of resistance to spot blotch was assessed. Spot blotch severity was significantly lower in plants from cv. BR‐18 compared to cv. Guamirim. Net carbon assimilation rate, stomatal conductance and concentrations of Chla, Chlab and carotenoids were significantly decreased from fungal infection. In contrast, internal CO₂ concentration was significantly increased from fungal infection in comparison to their non‐inoculated counterparts. Similarly, inoculation significantly reduced photochemical performance in the inoculated flag leaves in comparison to their non‐inoculated counterparts. However, plants from cv. BR‐18 were able to sustain greater functionality of the photosynthetic apparatus during fungal infection process compared to cv. Guamirim. The activities of SOD, POX, APX and CAT increased in inoculated flag leaves from both cultivars compared to non‐inoculated plants, and the highest increases were measured in cv. BR‐18. The greater activities of these enzymes were associated with a reduced H₂O₂ concentration in the inoculated flag leaves from cv. BR‐18, resulting, therefore, in a lower MDA concentration. Thus, a more efficient antioxidative system in flag leaves from cv. BR‐18 plays a pivotal role in removing the excess reactive oxygen species that were generated during the infection process of Bipolaris sorokiniana, therefore limiting cellular damage and largely preserving the photosynthetic efficiency of the infected flag leaves.     

Regulation of the photosynthetic electron transport and specific photoprotective mechanisms in <Emphasis Type="Italic">Ricinus communis</Emphasis> under drought and recovery

Ricinus communis is one of the major commercial non-edible oilseed crops grown in semiarid and arid environments worldwide and is reported as a drought tolerant species. Surprisingly, little is known about the mechanisms achieving this tolerance, especially in relation to photoprotection. The aim of this study was to analyze the association of the regulation of the photosynthetic electron transport and photoprotective mechanisms with drought tolerance in R. communis. Drought induced decreases in the relative water content, water potential and growth in R. communis exposed to 9 days of drought. After 6 days of rehydration, these parameters were completely recovered, demonstrating a potential of drought tolerance in this species. In addition, drought inhibited photosynthesis by stomatal and metabolic limitations (V _cmax, J _max, and Rubisco activity), with partial recovery after rehydration. Leaves displayed transient photoinhibition after 6 days of drought, which was completely recovered after 6 days of dehydration. The effective quantum yields and the electron transport rates of PSII and PSI were modulated to face drought avoiding the excess energy produced by decreases in CO₂ assimilation. NPQ was increased during drought, and it was maintained higher than control after the recovery treatment. In addition, the estimated cyclic electron flow was induced under drought and decreased after recovery. Photorespiration was also increased under drought and maintained at higher levels after the recovery treatment. Furthermore, antioxidative enzymes activities (SOD, APX, and CAT) were increased under drought to avoid ROS harmful effects. Altogether, we clearly showed that the modulation of photoprotective mechanisms and antioxidant enzymes are crucial to this species under drought. The implication of these strikingly strategies to drought tolerance is discussed in relation to agricultural and natural systems.