Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats

Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.     

Heavy Metals and Trace Element Concentrations in Intertidal Soils of Four Estuaries of SW Iberian Peninsula

Soils from four estuaries of SW Iberian Peninsula, affected by anthropogenic influence (urban, industrial and agricultural activities), were analyzed for the occurrence of a variety of metals and trace elements including Al, As, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, P, Pb, S and Zn. The soils presented very high levels of salinity (high concentrations of Na, K and Mg), organic matter and, consequently, of C and N concentrations. In contrast, very low values of CaCO₃, Ca and P were found. In addition, it should be highlighted that in certain localities (Piedras 1 and 2 and Guadiana in Huelva, Spain, and Ria Formosa, Faro, Portugal) the concentrations of Pb, S and Zn were extremely high, reaching levels of pollution.     

Determination of superoxide dismutase-like activity in some divalent metal saccharinates

The superoxide-dismutase-like activity of a series of divalent metal saccharinates of general stoichiometry [M^II(Sac)₂(H₂O)₄]·2H₂O (with M^II=Mn,Fe,Co,Ni,Cu,Zn) has been investigated using the nitroblue tetrazolium O ₂ ⁻ reduction assay. The results show that all these complexes possess the capability to dismutate the superoxide anion generated in the xanthine/xanthine oxidase system. Interestingly, the greatest activity is shown by the corresponding copper complex. The results are discussed and compared with those obtained for native superoxide dismutase, which was tested under the same experimental conditions. Dedicated to Prof. Pedro J. Aymonino on the occasion of his 65^th birthday.     

Do foliar endophytes affect grass litter decomposition? A microcosm approach using Lolium multiflorum

Symbiotic infection with fungal endophytes has been shown to decrease herbivory in several temperate grasses. We tested the hypothesis that foliar endophytes of grasses may also affect below-ground processes upon their host death, by altering the litter quality for detritivores or the microenvironment for decomposition. Microcosm–litterbag experiments were used to assess decay rates for litter produced by endophyte ( Neotyphodium sp.) infected vs uninfected Lolium multiflorum plants, and to examine endophyte-mediated effects of prior site occupants on current litter decomposition. We found that litter from endophyte-infected L. multiflorum decomposed more slowly than litter from endophyte-free conspecifics and from a naturally uninfected grass, Bromus unioloides . Furthermore, the endophyte–grass association modified the decomposition environment, so that B. unioloides litter decomposed faster when placed underneath a thick layer of endophyte-free L. multiflorum litter. Litter decay rates increased with the amount of root debris remaining in situ from the previous season, but were not affected by the infection status of prior site occupants. The lower decomposability of litter from infected L. multiflorum plants persisted across a range of microenvironments, as determined by different amounts of above-ground litter and soil moisture conditions. Endophyte infection tended to reduce the N content of decaying litter; however, litter N and C/N ratio mainly accounted for interspecific differences in decomposition. Our results imply that fungal endophytes not only can affect herbivory food chains, but also soil organisms and the ecosystem processes they regulate. This study suggests a novel role for symbiotic foliar endophytes in linking above-ground and below-ground sub-systems.     

Synthesis and Cu(II) coordination of two new hexaamines containing alternated propylenic and ethylenic chains: Kinetic studies on pH-driven metal ion slippage movements

The synthesis of the open-chain and cyclic polyamines, 1,5,8,12,15,19-hexaazaheptadecane (L1) and 2,6,9,13,16,20-hexaaza[21]-(2,6)-pyridinophane (L2), are described. The protonation constants and interaction constants with Cu(II) have been determined by potentiometric measurements carried out at 298.1 K in 0.15 mol dm⁻³ NaClO₄. The values obtained are discussed as a function of the open-chain or cyclic nature of the ligands and compared with analogous polyamines containing different sets of hydrocarbon chains between the nitrogen donors. Kinetic studies on the acid-promoted dissociation of the Cu(II) complexes indicate that the mono and binuclear complexes of L1 decompose with different kinetics, a behavior unprecedented for open-chain polyamines. In contrast, the dissociation of the first metal ion is accelerated in the binuclear complexes of L2 and so, all the mono and binuclear complexes of L2 decompose with the same kinetics. The voltammetric response of Cu(II)-L1 and Cu(II)-L2 complexes has been studied in order to correlate electrochemical and structural data.     

Dual Cyclin-Binding Domains Are Required for p107 To Function as a Kinase Inhibitor

The retinoblastoma (pRB) family of proteins includes three proteins known to suppress growth of mammalian cells. Previously we had found that growth suppression by two of these proteins, p107 and p130, could result from the inhibition of associated cyclin-dependent kinases (cdks). One important unresolved issue, however, is the mechanism through which inhibition occurs. Here we present in vivo and in vitro evidence to suggest that p107 is a bona fide inhibitor of both cyclin A-cdk2 and cyclin E-cdk2 that exhibits an inhibitory constant (K_i) comparable to that of the cdk inhibitor p21/WAF1. In contrast, pRB is unable to inhibit cdks. Further reminiscent of p21, a second cyclin-binding site was mapped to the amino-terminal portions of p107 and p130. This amino-terminal domain is capable of inhibiting cyclin-cdk2 complexes, although it is not a potent substrate for these kinases. In contrast, a carboxy-terminal fragment of p107 that contains the previously identified cyclin-binding domain serves as an excellent kinase substrate although it is unable to inhibit either kinase. Clustered point mutations suggest that the amino-terminal domain is functionally important for cyclin binding and growth suppression. Moreover, peptides spanning the cyclin-binding region are capable of interfering with p107 binding to cyclin-cdk2 complexes and kinase inhibition. Our ability to distinguish between p107 and p130 as inhibitors rather than simple substrates suggests that these proteins may represent true inhibitors of cdks.