Differential signaling in presynaptic neurotransmitter release

Neuronal communication is tightly regulated by presynaptic signaling, thereby temporarily and locally secreting one or more transmitters in order to exert propagation or modulation of network activity. In the last 2 decades our insight into the molecular regulation of presynaptic transmitter vesicle traffic and fusion has exponentionally grown due to the identification of specific functional interactions between presynaptic proteins involved in these processes. In addition, a plethora of extracellular and intracellular messengers regulate neurotransmitter release, occasionally leading to short- or long-term adaptations of the synapse to altered environmental signals. Important in this respect is the ability of various nerve terminals to diverge their output by differentiation in secretion of co-localized transmitters. This divergence in presynaptic signaling may converge in the postsynaptic target neuron or spread to neighbouring cells. In this review differential presynaptic signaling mechanisms will be related to their potential divergent roles in transmitter release.Received 25 November 2004; received after revision 23 December 2004; accepted 28 December 2004 Available online 09 March 2005     

Vernix caseosa as a multi-component defence system based on polypeptides, lipids and their interactions

Vernix caseosa is a white cream-like substance that covers the skin of the foetus and the newborn baby. Recently, we discovered antimicrobial peptides/proteins such as LL-37 in vernix, suggesting host defence functions of vernix. In a proteomic approach, we have continued to characterize proteins in vernix and have identified 20 proteins, plus additional variant forms. The novel proteins identified, considered to be involved in host defence, are cystatin A, UGRP-1, and calgranulin A, B and C. These proteins add protective functions to vernix such as antifungal activity, opsonizing capacity, protease inhibition and parasite inactivation. The composition of the lipids in vernix has also been characterized and among these compounds the free fatty acids were found to exhibit antimicrobial activity. Interestingly, the vernix lipids enhance the antimicrobial activity of LL-37 in vitro, indicating interactions between lipids and antimicrobial peptides in vernix. In conclusion, vernix is a balanced cream of compounds involved in host defence, protecting the foetus and newborn against infection.     

An overview of the descent and landing of the Huygens probe on Titan

Titan, Saturn's largest moon, is the only Solar System planetary body other than Earth with a thick nitrogen atmosphere. The Voyager spacecraft confirmed that methane was the second-most abundant atmospheric constituent in Titan's atmosphere, and revealed a rich organic chemistry, but its cameras could not see through the thick organic haze. After a seven-year interplanetary journey on board the Cassini orbiter, the Huygens probe was released on 25 December 2004. It reached the upper layer of Titan's atmosphere on 14 January and landed softly after a parachute descent of almost 2.5 hours. Here we report an overview of the Huygens mission, which enabled studies of the atmosphere and surface, including in situ sampling of the organic chemistry, and revealed an Earth-like landscape. The probe descended over the boundary between a bright icy terrain eroded by fluvial activity--probably due to methane-and a darker area that looked like a river- or lake-bed. Post-landing images showed centimetre-sized surface details.     

Biodiversity conservation: uncertainty in predictions of extinction risk

Thomas et al. model species-distribution responses to a range of climate-warming scenarios and use a novel application of the species-area relationship to estimate that 15-37% of modelled species in various regions of the world will be committed to extinction by 2050. Although we acknowledge the efforts that they make to measure the uncertainties associated with different climate scenarios, species' dispersal abilities and z values (predictions ranged from 5.6% to 78.6% extinctions), we find that two additional sources of uncertainty may substantially increase the variability in predictions.     

Baker's yeast,an attractant for baiting traps for Chagas' disease vectors

We tested the attraction of volatile compounds, produced by the aerobic growth ofSaccharomyces cerevisiae on saccharose forTriatoma infestans. For these tests, we exploited the behavioural characteristic of these haematophagous insects of dropping when searching for food. In olfactometer assays, yeast cultures activated and attracted bugs as effectively as a mouse. The attraction of the cultures was significantly reduced when the carbon dioxide released was partially eliminated using potassium hydroxide. Yeast cultures were also tested as lures in a novel trap device. A baited device for trapping Chagas' disease vectors using the behavioural peculiarities ofT. infestans and this simple attractant is described.     

Coordinate expression of the murine Hox-5 complex homoeobox-containing genes during limb pattern formation

The homoebox-containing genes of the Hox-5 complex are expressed in different but overlapping domains in limbs during murine development. The more 5' the position of these genes in the complex, the later and more distal is their expression. Antero-posterior differences are also observed. A model is proposed that accounts for the establishment of these expression domains in relation to the existence of a morphogen released by the zone of polarizing activity. Comparison of these observations with the expression patterns of the genes of Hox complexes in the early embryo suggests that similar molecular mechanisms are involved in the positional signalling along the axes of both the embryonic trunk and the fetal limbs.     

Molecular basis of xeroderma pigmentosum group C DNA recognition by engineered meganucleases

Xeroderma pigmentosum is a monogenic disease characterized by hypersensitivity to ultraviolet light. The cells of xeroderma pigmentosum patients are defective in nucleotide excision repair, limiting their capacity to eliminate ultraviolet-induced DNA damage, and resulting in a strong predisposition to develop skin cancers. The use of rare cutting DNA endonucleases-such as homing endonucleases, also known as meganucleases-constitutes one possible strategy for repairing DNA lesions. Homing endonucleases have emerged as highly specific molecular scalpels that recognize and cleave DNA sites, promoting efficient homologous gene targeting through double-strand-break-induced homologous recombination. Here we describe two engineered heterodimeric derivatives of the homing endonuclease I-CreI, produced by a semi-rational approach. These two molecules-Amel3-Amel4 and Ini3-Ini4-cleave DNA from the human XPC gene (xeroderma pigmentosum group C), in vitro and in vivo. Crystal structures of the I-CreI variants complexed with intact and cleaved XPC target DNA suggest that the mechanism of DNA recognition and cleavage by the engineered homing endonucleases is similar to that of the wild-type I-CreI. Furthermore, these derivatives induced high levels of specific gene targeting in mammalian cells while displaying no obvious genotoxicity. Thus, homing endonucleases can be designed to recognize and cleave the DNA sequences of specific genes, opening up new possibilities for genome engineering and gene therapy in xeroderma pigmentosum patients whose illness can be treated ex vivo.     

Scale effects and human impact on the elevational species richness gradients

Despite two centuries of effort in characterizing environmental gradients of species richness in search of universal patterns, surprisingly few of these patterns have been widely acknowledged. Species richness along altitudinal gradients was previously assumed to increase universally from cool highlands to warm lowlands, mirroring the latitudinal increase in species richness from cool to warm latitudes. However, since the more recent general acceptance of altitudinal gradients as model templates for testing hypotheses behind large-scale patterns of diversity, these gradients have been used in support of all the main diversity hypotheses, although little consensus has been achieved. Here we show that when resampling a data set comprising 400,000 records for 3,046 Pyrenean floristic species at different scales of analysis (achieved by varying grain size and the extent of the gradients sampled), the derived species richness pattern changed progressively from hump-shaped to a monotonic pattern as the scale of extent diminished. Scale effects alone gave rise to as many conflicting patterns of species richness as had previously been reported in the literature, and scale effects lent significantly different statistical support to competing diversity hypotheses. Effects of scale on current studies may be affected by human activities, because montane ecosystems and human activities are intimately connected. This interdependence has led to a global reduction in natural lowland habitats, hampering our ability to detect universal patterns and impeding the search for universal diversity gradients to discover the mechanisms determining the distribution of biological diversity on Earth.