Nitric oxide and prostacyclin-dependent pathways involvement on in vitro induced hypothermia

Nitric oxide and prostacyclin are endogenous endothelium-derived vasodilators, but little information is available on their release during hypothermia. This study was carried out to test the hypothesis that endothelium may modulate vascular reactivity to decreased temperature changes. Segments of contracted (prostaglandin F(2alpha), 2x10(-6)M) canine coronary, femoral, and renal arteries, with and without endothelium, were in vitro ("organ chambers") exposed to progressive hypothermia (from 37 to 10 degrees C) in graded steps. The study is limited to physiological measurements of vascular tone, in the presence or absence of PGI(2) and/or NOS inhibitors, which show correlation with the relaxation. Hypothermia induced vasodilatation of vessels with intact endothelium, which became endothelium-independent below 20 degrees C. This vasodilatation began at 35 degrees C and, in the presence of indomethacin (2x10(-6)M), at 30 degrees C. Endothelium-dependent vasodilatation to hypothermia was blocked by L-NMMA or L-NOARG (10(-5)M), two competitive inhibitors of nitric oxide synthase (n=5 each, P<0.05). Oxyhemoglobin (2x10(-6)M) also inhibited vasodilatation induced by hypothermia (n=6, P<0.05). Pretreatment with either atropine or pirenzepine (10(-6)M) inhibited hypothermia-mediated vasodilatation (n=5 each, P<0.05). The present in vitro study concluded that the endothelium is sensitive to temperature variations and indicated that PGI(2) and NO-dependent pathways may be involved endothelium-dependent relaxation to hypothermia. The endothelium-dependent vasodilatation to hypothermia, in systemic and coronary arteries, is mediated by the M1 muscarinic receptor.     

Evidence for new Neanderthal teeth in Tabun Cave (Israel) by the application of self-organizing maps (SOMs)

Morphological and metrical study suggested that seven human teeth from Tabun Cave, Israel were part of the upper dentition of a single, probably Neanderthal, individual renumbered as Tabun BC7. An enamel fragment gave ESR age estimates of 82+/-14 ka (early U-uptake) and 92+/-18 ka (linear uptake) and an age estimate of 90(+30)(-16) ka using U-series disequilibrium. Although metrical analyses suggested Neanderthal affinities, definitive assessment was difficult as the values often fell into the ranges of both Neanderthal and Levantine early modern human samples. Therefore, two further classification analyses were conducted (neural networks using self-organizing maps and homogeneity analysis). Both identify Tabun BC7 as a Neanderthal. Neural networks are a promising tool for paleoanthropological studies as they can provide reliable classifications even with incomplete data.     

An inquiry into the selective protection of glycine during the radiolysis of glycine-alanine mixtures in aqueous solutions and its implications to the preservation of optically active amino acids in the early earth

Akaboshi et al. (1990) has found an unexpected protection of the achiral amino acid, glycine, towards ionizing radiation at the expense of the selective destruction of the chiral amino acids, alanine and aspartic acid. The present work examines the mechanism of this protection for the case of alanine. We have developed a computer model for the radiolysis of glycine, alanine and glycine-alanine mixtures in aqueous solution. It is established that this protection is due in part to the reaction of the α-radical of glycine with alanine to regenerate a more stable α-radical, according to the following reaction, $$ \cdot CH(NH_3^ + )CO_2^ - + CH_3 CH(NH_3^ + )CO_2^ - \to CH_2 (NH_3^ + )CO_2^ - + CH_3 \dot C(NH_3^ + )CO_2^ -$$ The rate constant of this reaction was estimated to be ≤10⁴M^-1s^-1. The implications for this selective protection of glycine are considered for a hypothetical case in which there would be an enrichment of about 10% ofL-alanine in the primitive ocean and taking the glycine/alanine ratios obtained in CH₄-and CO₂- dominated atmospheres using electric discharge experiments. It is predicted that alanine would be rapidly destroyed and radioracemized in spite of the fact that the concentration of alanine is equal or significantly lower than that of glycine. Assuming that chiral amino acids were a prerequisite for the origin of life, it can be deduced that life could have appeared in a relatively short period of time unless there was a constant supply of optical amino acids from extraterrestrial sources.     

Photosynthetic Light Responses May Explain Vertical Distribution of Hymenophyllaceae Species in a Temperate Rainforest of Southern Chile

Some epiphytic Hymenophyllaceae are restricted to lower parts of the host (<60 cm; 10–100 μmol photons m^-2 s^-1) in a secondary forest of Southern Chile; other species occupy the whole host height (≥10 m; max PPFD >1000 μmol photons m^-2 s^-1). Our aim was to study the photosynthetic light responses of two Hymenophyllaceae species in relation to their contrasting distribution. We determined light tolerance of Hymenoglossum cruentum and Hymenophyllum dentatum by measuring gas exchange, PSI and PSII light energy partitioning, NPQ components, and pigment contents. H. dentatum showed lower maximum photosynthesis rates (A_max) than H. cruentum, but the former species kept its net rates (A_n) near A_max across a wide light range. In contrast, in the latter one, A_n declined at PPFDs >60 μmol photons m^-2 s^-1. H. cruentum, the shadiest plant, showed higher chlorophyll contents than H. dentatum. Differences in energy partitioning at PSI and PSII were consistent with gas exchange results. H. dentatum exhibited a higher light compensation point of the partitioning of absorbed energy between photochemical Y(PSII) and non-photochemical Y(NPQ) processes. Hence, both species allocated energy mainly toward photochemistry instead of heat dissipation at their light saturation points. Above saturation, H. cruentum had higher heat dissipation than H. dentatum. PSI yield (YPSI) remained higher in H. dentatum than H. cruentum in a wider light range. In both species, the main cause of heat dissipation at PSI was a donor side limitation. An early dynamic photo-inhibition of PSII may have caused an over reduction of the Qa⁺ pool decreasing the efficiency of electron donation to PSI. In H. dentatum, a slight increase in heat dissipation due to acceptor side limitation of PSI was observed above 300 μmol photons m^-2s^-1. Differences in photosynthetic responses to light suggest that light tolerance and species plasticity could explain their contrasting vertical distribution.     

Spatial and altitudinal bioclimatic zones of the Italian peninsula identified from a beech (Fagus sylvatica L.) tree-ring network

A network of 24 beech (Fagus sylvatica L.) tree-ring chronologies has been developed for the Italian peninsula. Principal component and cluster analyses were used to identify geographical and altitudinal patterns of tree growth. Correlations and response functions were then applied to the main modes of tree-ring variability to uncover climatic signals. In a landscape occupied by humans for millennia, this approach provided a detailed quantitative ecological characterization of forest types. Altitude was significantly correlated with dendrochronological parameters. The Alps and northern Apennines could be distinguished from the central-southern Apennines. In central Italy, we recognized three different vegetation belts occupied by beech forests, from low- to high-elevation sites. Summer drought impacted beech growth with different intensity at different elevations, depending on the onset and duration of the growing season. Moreover, low-elevation beech forests showed a distinct late spring climate signal, which was opposite to that of high-elevation sites. The coherent geographical and ecological patterns of tree-ring variability suggest that dendrochronological networks help define bioclimatic zones and forest types.     

Characterization of the effects of a polyunsaturated fatty acid (PUFA) on mitochondrial bioenergetics of chronologically aged yeast

Increased membrane unsaturation has been associated with shorter longevity due to higher sensitivity to lipid peroxidation (LP) leading to enhanced mitochondrial dysfunction and ROS overproduction. However, the role of LP during aging has been put in doubt along with the participation of electron leak at the electron transport chain (ETC) in ROS generation in aged organisms. Thus, to test these hypothesis and gain further information about how minimizing LP preserves ETC function during aging, we studied the effects of α-linolenic acid (C18:3) on in situ mitochondrial ETC function, ROS production and viability of chronologically aged cells of S. cerevisiae, whose membranes are intrinsically resistant to LP due to the lack of PUFA. Increased sensitivity to LP was observed in cells cultured with C18:3 at 6 days of aging. This was associated with higher viability loss, dissipated membrane potential, impaired respiration and increased ROS generation, being these effects more evident at 28 days. However, at this point, lower sensitivity to LP was observed without changes in the membrane content of C18:3, suggesting the activation of a mechanism counteracting LP. The cells without C18:3 display better viability and mitochondrial functionality with lower ROS generation even at 28 days of aging and this was attributed to full preservation of complex III activity. These results indicate that the presence of PUFA in membranes enhances ETC dysfunction and electron leak and suggest that complex III is crucial to preserve membrane potential and to maintain a low rate of ROS production during aging.     

Fine Mapping and Functional Analysis of the Multiple Sclerosis Risk Gene CD6

CD6 has recently been identified and validated as risk gene for multiple sclerosis (MS), based on the association of a single nucleotide polymorphism (SNP), rs17824933, located in intron 1. CD6 is a cell surface scavenger receptor involved in T-cell activation and proliferation, as well as in thymocyte differentiation. In this study, we performed a haptag SNP screen of the CD6 gene locus using a total of thirteen tagging SNPs, of which three were non-synonymous SNPs, and replicated the recently reported GWAS SNP rs650258 in a Spanish-Basque collection of 814 controls and 823 cases. Validation of the six most strongly associated SNPs was performed in an independent collection of 2265 MS patients and 2600 healthy controls. We identified association of haplotypes composed of two non-synonymous SNPs [rs11230563 (R225W) and rs2074225 (A257V)] in the 2^nd SRCR domain with susceptibility to MS (P _{max(T) permutation} = 1×10⁻⁴). The effect of these haplotypes on CD6 surface expression and cytokine secretion was also tested. The analysis showed significantly different CD6 expression patterns in the distinct cell subsets, i.e. – CD4⁺ naïve cells, P = 0.0001; CD8⁺ naïve cells, P<0.0001; CD4⁺ and CD8⁺ central memory cells, P = 0.01 and 0.05, respectively; and natural killer T (NKT) cells, P = 0.02; with the protective haplotype (RA) showing higher expression of CD6. However, no significant changes were observed in natural killer (NK) cells, effector memory and terminally differentiated effector memory T cells. Our findings reveal that this new MS-associated CD6 risk haplotype significantly modifies expression of CD6 on CD4⁺ and CD8⁺ T cells.