Transglutaminase participates in the blockade of neurotransmitter release by tetanus toxin: evidence for a novel biological function

The aim of this study was to collect evidences on the role of transglutaminase (TG, E.C.2.3.2.13) in the antineoplastic properties exerted by nimesulide (NMS), a non-steroidal anti-inflammatory drug, on murine B16-F10 melanoma cells. Treatment of melanoma cells with nimesulide produces a considerable reduction of cell proliferation, paralleled by a remarkable decrease of the intracellular concentration of polyamines spermidine and spermine. NMS treatment induces cancer cell differentiation, likely through the observed enhancement of TG and tyrosinase activities and increase of melanin production, well known markers of melanocyte differentiation. The overall results highlight the possibility that nimesulide acts as antineoplastic agent likely through the induction of intracellular TG activity.     

Fundulus as the premier teleost model in environmental biology: opportunities for new insights using genomics

A strong foundation of basic and applied research documents that the estuarine fish Fundulus heteroclitus and related species are unique laboratory and field models for understanding how individuals and populations interact with their environment. In this paper we summarize an extensive body of work examining the adaptive responses of Fundulus species to environmental conditions, and describe how this research has contributed importantly to our understanding of physiology, gene regulation, toxicology, and ecological and evolutionary genetics of teleosts and other vertebrates. These explorations have reached a critical juncture at which advancement is hindered by the lack of genomic resources for these species. We suggest that a more complete genomics toolbox for F. heteroclitus and related species will permit researchers to exploit the power of this model organism to rapidly advance our understanding of fundamental biological and pathological mechanisms among vertebrates, as well as ecological strategies and evolutionary processes common to all living organisms.     

Species distribution,ecology, abundance,body size and phylogeny originate interrelated rarity patterns at regional scale

The most pervasive macroecological patterns concern (1) the frequency distribution of range size, (2) the relationship between range size and species abundance and (3) the effect of body size on range size. We investigated these patterns at a regional scale using the tenebrionid beetles of Latium (Central Italy). For this, we calculated geographical range size (no. of 10‐km square cells), ecological tolerance (no. of phytoclimatic units) and abundance (no. of sampled individuals) using a large database containing 3561 georeferenced records for 84 native species. For each species, we also calculated body mass and its ‘phylogenetic diversity’ on the basis of cladistic relationships. Frequency distribution of range size followed a log‐normal distribution as found in many other animal groups. However, a log‐normal distribution accommodated well the frequency distribution of ecological tolerance, a so far unexplored issue. Range size was correlated with abundance and ecological tolerance, thus supporting the hypothesis that a positive correlation between distribution and abundance is a reflection of interspecific differences in ecological specialization. Larger species tended to have larger ranges and broader ecological tolerance. However, contrary to what known in most vertebrates, not only small‐sized, but also many medium‐to‐large‐sized species exhibited great variability in their range size, probably because tenebrionids are not so strictly influenced by body size constraints (e.g. home ranges) as vertebrates. Moreover, in contrast to other animals, tenebrionid body size does not influence species abundances, probably because these detritivorous animals are not strongly regulated by competition. Finally, contrary to the assumption that rare species should be mainly found among lineages that split from basal nodes, rarity of a tenebrionid species was not influenced by the phylogenetic position of its tribe. However, lineages that split from more basal nodes had lower variability in terms of species geographical distribution, ecological tolerance and abundance, which suggests that lineages that split from more basal nodes are not only morphologically conservative but also tend to have an ecological ‘inertia’.     

Reinvestigation of a selenopeptide with purportedly high glutathione peroxidase activity

A 15-amino acid long selenopeptide (15SeP) was recently reported to possess nearly the same catalytic activity as glutathione peroxidase (Gpx) for the reduction of hydrogen peroxide by glutathione (Sun, Y., Li, T. Y., Chen, H., Zhang, K., Zheng, K. Y., Mu, Y., Yan, G. L., Li, W., Shen, J. C., and Luo, G. M. (2004) J. Biol. Chem. 279, 37235-37240). Such a finding is startling considering the high efficiency of the natural enzyme and the modest catalytic properties of most short peptides. As 15SeP had been subjected only to limited chemical characterization, we prepared it by a new route involving selenocysteine-mediated native chemical ligation. High resolution matrix-assisted laser desorption ionization mass spectrometry confirmed the identity of the reaction product, whereas circular dichroism spectroscopy showed that 15SeP assumes a random coil conformation in solution. Although low levels of peroxidase activity were detectable under standard assay conditions, the peptide is >5 orders of magnitude less active than native Gpx. Our observations are incompatible with claims ascribing remarkable catalytic properties to 15SeP and suggest that the efficiency of Gpx derives from its well defined three-dimensional structure.     

Cells migrating to sites of tissue damage in response to the danger signal HMGB1 require NF-kappaB activation

Tissue damage is usually followed by healing, as both differentiated and stem cells migrate to replace dead or damaged cells. Mesoangioblasts (vessel-associated stem cells that can repair muscles) and fibroblasts migrate toward soluble factors released by damaged tissue. Two such factors are high mobility group box 1 (HMGB1), a nuclear protein that is released by cells undergoing unscheduled death (necrosis) but not by apoptotic cells, and stromal derived factor (SDF)-1/CXCL12. We find that HMGB1 activates the canonical nuclear factor kappaB (NF-kappaB) pathway via extracellular signal-regulated kinase phosphorylation. NF-kappaB signaling is necessary for chemotaxis toward HMGB1 and SDF-1/CXCL12, but not toward growth factor platelet-derived growth factor, formyl-met-leu-phe (a peptide that mimics bacterial invasion), or the archetypal NF-kappaB-activating signal tumor necrosis factor alpha. In dystrophic mice, mesoangioblasts injected into the general circulation ingress inefficiently into muscles if their NF-kappaB signaling pathway is disabled. These findings suggest that NF-kappaB signaling controls tissue regeneration in addition to early events in inflammation.     

The conformational and property space of acetylcholine bound to muscarinic receptors: an entropy component accounts for the subtype selectivity of acetylcholine

The conformational behavior of receptor-bound acetylcholine (ACh) was investigated by molecular dynamics simulations. Based on the great similarity among muscarinic receptors, the study was focused on the human M(1), M(2), and M(5) receptors as previously modeled by us. The results showed that receptor-bound ACh was not frozen in a single preferred conformation but preserved an unexpected fraction of its conformational space. However, there were marked differences between the three receptors since the ligand was mostly trans in the M(1) receptor, equally distributed among trans and gauche conformers in M(2), and exclusively gauche in the M(5); the greater flexibility of M(2)-bound ACh was paralleled by the greater flexibility of the occupied M(2) binding site. By contrast, the property space of receptor-bound ACh, and particularly its virtual (computed, conformation-dependent) lipophilicity, was restricted to relatively narrow ranges optimal for successful interaction. Experimental binding investigations to the individual human M(1), M(2), and M(5) muscarinic receptors showed ACh to have a 10-fold higher affinity for the M(2) compared to the M(1) and M(5) receptors. This selectivity was not confirmed by the calculated binding scores, a fact postulated to be caused by the absence of an entropy component in such binding scores. Indeed, the Shannon entropy of all geometric and physicochemical properties monitored were markedly higher in M(2)-bound ACh compared to M(1)-bound and M(5)-bound ACh. This finding suggests that the selectivity profile of acetylcholine for the M(2) receptor is largely entropy-driven, a fact that might explain the intrinsic difficulty to design subtype-selective muscarinic agonists.     

The minimum information required for reporting a molecular interaction experiment (MIMIx)

A wealth of molecular interaction data is available in the literature, ranging from large-scale datasets to a single interaction confirmed by several different techniques. These data are all too often reported either as free text or in tables of variable format, and are often missing key pieces of information essential for a full understanding of the experiment. Here we propose MIMIx, the minimum information required for reporting a molecular interaction experiment. Adherence to these reporting guidelines will result in publications of increased clarity and usefulness to the scientific community and will support the rapid, systematic capture of molecular interaction data in public databases, thereby improving access to valuable interaction data.     

Transplantation of Foetal Neural Stem Cells into the Rat Hippocampus During Trimethyltin-Induced Neurodegeneration

The present study investigates the survival and fate of neural stem cells/progenitor cells (NSC/NPCs) homografted into the hippocampus of rats treated with trimethyltin (TMT), a potent neurotoxicant considered a useful tool to obtain a well characterized model of neurodegeneration, to evaluate their possible role in the reparative mechanisms that accompany neurodegenerative events. NSC/NPCs expressing eGFP by lentivirus-mediated infection were stereotaxically grafted into the hippocampus of TMT-treated animals and controls. Two weeks after transplantation surviving NSC/NPCs were detectable in 60% of TMT-treated animals and 30% of controls, while 30 days after transplantation only 40% of TMT-treated animals showed surviving grafted cells, which were undetectable in controls. At both times investigated, while grafted NSC/NPCs differentiated into neurons or astrocytes could be observed in addition to undifferentiated NSC/NPCs, we did not find evidence of structural integration of grafted cells into the main site of hippocampal lesion leading to appreciable repair. Maria Concetta Geloso and Stefano Giannetti contributed equally to this work.     

Copepods in spring annual sea ice at Terra Nova Bay (Ross Sea,Antarctica)

The aim of this study was to investigate patterns of abundance, distribution, temporal changes and species composition of the dominant ice-associated copepods in the spring annual pack ice, platelet ice and water column at Terra Nova Bay, Ross Sea, during late spring 1997. Ice cores were drilled for temporal and spatial scales. Stephos longipes and Harpacticus furcifer dominated the sea ice meiofauna in terms of numbers in the lower few centimeters of the bottom ice associated with high chlorophyll a and phaeopigment levels. Nauplii dominated the S. longipes population (91.6%) and occurred in extremely high concentrations. In contrast, copepodids were the dominant stages in H. furcifer. How H. furcifer carries out its entire life cycle and how it differs from ecologically similar species such as Drescheriella glacialis should be examined in more detail.