Protein synthesis inhibitors, gene superinduction and memory: too little or too much protein?
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To date, the effects of protein synthesis inhibitors (PSI) in learning and memory processes have been attributed to translational arrest and consequent inhibition of de novo protein synthesis. Here we argue that amnesia produced by PSI can be the direct result of their abnormal induction of mRNA-a process termed gene superinduction. This action exerted by PSI involves an abundant and prolonged accumulation of mRNA transcripts of genes that are normally transiently induced. We summarize experimental evidence for the multiple mechanisms and signaling pathways mediating gene superinduction and consider its relevance for PSI-induced amnesia. This mechanistic alternative to protein synthesis inhibition is compared to models of electroconvulsive seizures and fragilexsyndrome associated with enhanced mRNA/protein levels and cognitive deficits. (+info)
Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial.
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A fatal transmissible tumor spread between individuals by biting has emerged in the Tasmanian devil (Sarcophilus harrisii), a carnivorous marsupial. Here we provide genetic evidence establishing that the tumor is clonal and therefore foreign to host devils. Thus, the disease is highly unusual because it is not just a tumor but also a tissue graft, passed between individuals without invoking an immune response. The MHC plays a key role in immune responses to both tumors and grafts. The most common mechanism of immune evasion by tumors is down-regulation of classical cell surface MHC molecules. Here we show that this mode of immune escape does not occur. However, because the tumor is a graft, it should still be recognized and rejected by the host's immune system due to foreign cell surface antigens. Mixed lymphocyte responses showed a lack of alloreactivity between lymphocytes of different individuals in the affected population, indicating a paucity of MHC diversity. This result was verified by genotyping, providing a conclusive link between a loss of MHC diversity and spread of a disease through a wild population. This novel disease arose as a direct result of loss of genetic diversity and the aggressive behavior of the host species. The neoplastic clone continues to spread although the population, and, without active disease control by removal of affected animals and the isolation of disease-free animals, the Tasmanian devil faces extinction. (+info)
BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory?
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It is generally believed that late-phase long-term potentiation (L-LTP) and long-term memory (LTM) require new protein synthesis. Although the full complement of proteins mediating the long-lasting changes in synaptic efficacy have yet to be identified, several lines of evidence point to a crucial role for activity-induced brain-derived neurotrophic factor (BDNF) expression in generating sustained structural and functional changes at hippocampal synapses thought to underlie some forms of LTM. In particular, BDNF is sufficient to induce the transformation of early to late-phase LTP in the presence of protein synthesis inhibitors, and inhibition of BDNF signaling impairs LTM. Despite solid evidence for a critical role of BDNF in L-LTP and LTM, many issues are not resolved. Given that BDNF needs to be processed in Golgi outposts localized at the branch point of one or few dendrites, a conceptually challenging problem is how locally synthesized BDNF in dendrites could ensure synapse-specific modulation of L-LTP. An interesting alternative is that BDNF-TrkB signaling is involved in synaptic tagging, a prominent hypothesis that explains how soma-derived protein could selectively modulate the tetanized (tagged) synapse. Finally, specific roles of BDNF in the acquisition, retention or extinction of LTM remain to be established. (+info)
A long-term association between global temperature and biodiversity, origination and extinction in the fossil record.
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The past relationship between global temperature and levels of biological diversity is of increasing concern due to anthropogenic climate warming. However, no consistent link between these variables has yet been demonstrated. We analysed the fossil record for the last 520 Myr against estimates of low latitude sea surface temperature for the same period. We found that global biodiversity (the richness of families and genera) is related to temperature and has been relatively low during warm 'greenhouse' phases, while during the same phases extinction and origination rates of taxonomic lineages have been relatively high. These findings are consistent for terrestrial and marine environments and are robust to a number of alternative assumptions and potential biases. Our results provide the first clear evidence that global climate may explain substantial variation in the fossil record in a simple and consistent manner. Our findings may have implications for extinction and biodiversity change under future climate warming. (+info)
The importance of habitat and life history to extinction risk in sharks, skates, rays and chimaeras.
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We compared life-history traits and extinction risk of chondrichthyans (sharks, rays and chimaeras), a group of high conservation concern, from the three major marine habitats (continental shelves, open ocean and deep sea), controlling for phylogenetic correlation. Deep-water chondrichthyans had a higher age at maturity and longevity, and a lower growth completion rate than shallow-water species. The average fishing mortality needed to drive a deep-water chondrichthyan species to extinction (Fextinct) was 38-58% of that estimated for oceanic and continental shelf species, respectively. Mean values of Fextinct were 0.149, 0.250 and 0.368 for deep-water, oceanic and continental shelf species, respectively. Reproductive mode was an important determinant of extinction risk, while body size had a weak effect on extinction risk. As extinction risk was highly correlated with phylogeny, the loss of species will be accompanied by a loss of phylogenetic diversity. Conservation priority should not be restricted to large species, as is usually suggested, since many small species, like those inhabiting the deep ocean, are also highly vulnerable to extinction. Fishing mortality of deep-water chondrichthyans already exploited should be minimized, and new deep-water fisheries affecting chondrichthyans should be prevented. (+info)
Discordance between living and death assemblages as evidence for anthropogenic ecological change.
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Mismatches between the composition of a time-averaged death assemblage (dead remains sieved from the upper mixed-zone of the sedimentary column) and the local living community are typically attributed to natural postmortem processes. However, statistical analysis of 73 molluscan data sets from estuaries and lagoons reveals significantly poorer average "live-dead agreement" in settings of documented anthropogenic eutrophication (AE) than in areas where AE and other human impacts are negligible. Taxonomic similarity of paired live and dead species lists declines steadily among areas as a function of AE severity, and, for data sets comprising only adults, rank-order agreement in species abundance drops where AE is suspected. The observed live-dead differences in composition are consistent with eutrophication (anomalous abundance of seagrass-dwellers and/or scarcity of organic-loving species in the death assemblage), suggesting compositional inertia of death assemblages to recent environmental change. Molluscan data sets from open shelf settings (n = 34) also show higher average live-dead discordance in areas of AE. These results indicate that (i) live-dead discordance in surficial grab samples provides valuable evidence for strong anthropogenic modification of benthic communities, (ii) actualistic estimates of the ecological fidelity of molluscan death assemblages tend to be erroneously pessimistic when conducted in nonpristine settings, and (iii) based on their high fidelity in pristine study areas, death assemblages are a promising means of reconstructing otherwise elusive preimpact ecological baselines from sedimentary records. (+info)
Phylogeny and divergence of the pinnipeds (Carnivora: Mammalia) assessed using a multigene dataset.
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BACKGROUND: Phylogenetic comparative methods are often improved by complete phylogenies with meaningful branch lengths (e.g., divergence dates). This study presents a dated molecular supertree for all 34 world pinniped species derived from a weighted matrix representation with parsimony (MRP) supertree analysis of 50 gene trees, each determined under a maximum likelihood (ML) framework. Divergence times were determined by mapping the same sequence data (plus two additional genes) on to the supertree topology and calibrating the ML branch lengths against a range of fossil calibrations. We assessed the sensitivity of our supertree topology in two ways: 1) a second supertree with all mtDNA genes combined into a single source tree, and 2) likelihood-based supermatrix analyses. Divergence dates were also calculated using a Bayesian relaxed molecular clock with rate autocorrelation to test the sensitivity of our supertree results further. RESULTS: The resulting phylogenies all agreed broadly with recent molecular studies, in particular supporting the monophyly of Phocidae, Otariidae, and the two phocid subfamilies, as well as an Odobenidae + Otariidae sister relationship; areas of disagreement were limited to four more poorly supported regions. Neither the supertree nor supermatrix analyses supported the monophyly of the two traditional otariid subfamilies, supporting suggestions for the need for taxonomic revision in this group. Phocid relationships were similar to other recent studies and deeper branches were generally well-resolved. Halichoerus grypus was nested within a paraphyletic Pusa, although relationships within Phocina tend to be poorly supported. Divergence date estimates for the supertree were in good agreement with other studies and the available fossil record; however, the Bayesian relaxed molecular clock divergence date estimates were significantly older. CONCLUSION: Our results join other recent studies and highlight the need for a re-evaluation of pinniped taxonomy, especially as regards the subfamilial classification of otariids and the generic nomenclature of Phocina. Even with the recent publication of new sequence data, the available genetic sequence information for several species, particularly those in Arctocephalus, remains very limited, especially for nuclear markers. However, resolution of parts of the tree will probably remain difficult, even with additional data, due to apparent rapid radiations. Our study addresses the lack of a recent pinniped phylogeny that includes all species and robust divergence dates for all nodes, and will therefore prove indispensable to comparative and macroevolutionary studies of this group of carnivores. (+info)
A new estimate of afrotherian phylogeny based on simultaneous analysis of genomic, morphological, and fossil evidence.
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BACKGROUND: The placental mammalian clade Afrotheria is now supported by diverse forms of genomic data, but interordinal relationships within, and morphological support for, the group remains elusive. As a means for addressing these outstanding problems, competing hypotheses of afrotherian interordinal relationships were tested through simultaneous parsimony analysis of a large data set (> 4,590 parsimony informative characters) containing genomic data (> 17 kb of nucleotide data, chromosomal associations, and retroposons) and 400 morphological characters scored across 16 extant and 35 extinct afrotherians. RESULTS: Parsimony analysis of extant taxa alone recovered the interordinal topology (Afrosoricida, ((Macroscelidea, Tubulidentata), (Hyracoidea, (Proboscidea, Sirenia)))). Analysis following addition of extinct taxa instead supported Afroinsectivora (Afrosoricida + Macroscelidea) and Pseudoungulata (Tubulidentata + Paenungulata), as well as Tethytheria (Proboscidea + Sirenia). This latter topology is, however, sensitive to taxon deletion and different placements of the placental root, and numerous alternative interordinal arrangements within Afrotheria could not be statistically rejected. Relationships among extinct stem members of each afrotherian clade were more stable, but one alleged stem macroscelidean (Herodotius) never grouped with that clade and instead consistently joined pseudoungulates or paenungulates. When character transformations were optimized onto a less resolved afrotherian tree that reflects uncertainty about the group's interordinal phylogeny, a total of 21 morphological features were identified as possible synapomorphies of crown Afrotheria, 9 of which optimized unambiguously across all character treatments and optimization methods. CONCLUSION: Instability in afrotherian interordinal phylogeny presumably reflects rapid divergences during two pulses of cladogenesis - the first in the Late Cretaceous, at and just after the origin of crown Afrotheria, and the second in the early Cenozoic, with the origin of crown Paenungulata. Morphological evidence for divergences during these two pulses either never existed or has largely been "erased" by subsequent evolution along long ordinal branches. There may, nevertheless, be more morphological character support for crown Afrotheria than is currently assumed; the features identified here as possible afrotherian synapomorphies can be further scrutinized through future phylogenetic analyses with broader taxon sampling, as well as recovery of primitive fossil afrotherians from the Afro-Arabian landmass, where the group is likely to have first diversified. (+info)