Phylogenetic analyses of Saussurea sect. Pseudoeriocoryne (Asteraceae : Cardueae) based on chloroplast DNA trnL-F sequences

The genus Saussurea is distributed mainly in the temperate and subarctic regions of Eurasia and consists of about 300 species classified into six subgenera and 20 sections. Sect. Pseudoeriocoryne in the subgenus Eriocoryne comprises four species, and is delimited mainly by acaulescence and an inflorescence with congested capitula surrounded by a rosette of leaves. All of these species are endemic to the and Qinghai-Tibet Plateau. Sequences from the chloroplast DNA trnL-F region were obtained for the four species in this section and 26 other species from four subgenera of Saussurea to resolve phylogenetic relationships among these species and to determine whether the shared characters that define sect. Pseudoeriocoryne are synapomorphic or were acquired by convergent evolution. The resulting phylogenies indicated that Saussurea sect. Pseudoeriocoryne as traditionally defined does not constitute a monophyletic group and that each of its species belongs to separate clades. Furthermore, none of these species showed a close relationship with the other species of subgenus Eriocoryne. Our results further indicated that none of the investigated subgenera are monophyletic, and that species from different subgenera clustered together. All these conclusions are provisional and their confirmation would require stronger phylogenetic support. Two possible explanations are suggested for low sequence divergence, poor resolution of internal clades and clustering of species with the rather distinct morphology of Saussurea detected in the present study. The first is rapid radiation and diversification triggered by fast habitat fragmentation due to the recent lifting of the Qinghai-Tibet Plateau and the Quaternary climate oscillations. This could have led to rapid morphological divergence while sequences diverged very little, and also caused the convergent acquisition of similar characteristics in unrelated lineages due to similar selection pressures. The second possible explanation is that both introgressive hybridization and reticulate evolution might have caused the transferring of cpDNA sequences between morphologically dissimilar species, thus leading to homogenization of sequences between lineages. (C) 2004 Elsevier Ltd. All rights reserved.

Phylogenetic relationships of five pika species (genus Ochotona) based on mitochondrial DNA restriction maps

Restriction site mapping of mitochondrial DNA (mtDNA) with 16 restriction endonucleases was used to examine the phylogenetic relationships of Ochotona cansus, O. huangensis, O. thibetana, O. curzoniae and O. erythrotis. A 1-kb length variation between O. erythrotis of subgenus Pika and other four species of subgenus Ochotona was observed, which may be a useful genetic marker for identifying the two subgenera. The phylogenetic tree constructed using PAUP based on 61 phylogenetically informative sites suggests that O. erythrotis diverged first, followed by O. cansus, while O. curzoniae and O. huangensis are sister taxa related to O. thibetana, The results indicate that both O. cansus and O. huangensis should be treated as independent species. If the base substitution rate of pikas mtDNA was 2% per million years, then the divergence time of the two subgenera, Pika and Ochotana, is about 8.8 Ma ago of late Miocence, middle Bao-dian of Chinese mammalian age, and the divergence of the four species in subgenus Ochotona would have occurred about 2.5 - 4.2 Ma ago, Yushean of Chinese mammalian age. This calculation appears to be substantiated by the fossil record.

Identification, Selection, and Enrichment of Cardiomyocyte Precursors

The large-scale production of cardiomyocytes is a key step in the development of cell therapy and tissue engineering to treat cardiovascular diseases, particularly those caused by ischemia. the main objective of this study was to establish a procedure for the efficient production of cardiomyocytes by reprogramming mesenchymal stem cells from adipose tissue. First, lentiviral vectors expressing neoR and GFP under the control of promoters expressed specifically during cardiomyogenesis were constructed to monitor cell reprogramming into precardiomyocytes and to select cells for amplification and characterization. Cellular reprogramming was performed using 5'-azacytidine followed by electroporation with plasmid pOKS2a, which expressed Oct4, Sox2, and Klf4. Under these conditions, GFP expression began only after transfection with pOKS2a, and less than 0.015% of cells were GFP(+). These GFP(+) cells were selected for G418 resistance to find molecular markers of cardiomyocytes by RT-PCR and immunocytochemistry. Both genetic and protein markers of cardiomyocytes were present in the selected cells, with some variations among them. Cell doubling time did not change after selection. Together, these results indicate that enrichment with vectors expressing GFP and neoR under cardiomyocyte-specific promoters can produce large numbers of cardiomyocyte precursors (CMPs), which can then be differentiated terminally for cell therapy and tissue engineering.

Relação entre a Infeção por Escherichia coli Aderente-Invasina e a Doença de Crohn

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

The role of mitogen activated protein kinase phosphatase-1 in neurotoxic and inflammatory-induced changes in the development of midbrain dopaminergic neurons: relevance to Parkinson’s disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by the loss of midbrain dopaminergic neurons from the substantia nigra pars compacta(SNpc), which results in motor, cognitive and psychiatric symptoms. Evidence supports a role for the mitogen-activated protein kinase p38 in the demise of dopaminergic neurons, while mitogen-activated protein kinase phosphatase-1 (MKP-1), which negatively regulates p38 activity, has not yet been investigated in this context. Inflammation may also be associated with the neuropathology of PD due to evidence of increased levels of proinflammatory cytokines such as interleukin-1β (IL-1β) within the SNpc. Because of the specific loss of dopaminergic neurons in a discreet region of the brain, PD is considered a suitable candidate for cell replacement therapy but challenges remain to optimise dopaminergic cell survival and morphological development. The present thesis examined the role of MKP-1 in neurotoxic and inflammatory-induced changes in the development of midbrain dopaminergic neurons. We show that MKP-1 is expressed in dopaminergic neurons cultured from embryonic day (E) 14 rat ventral mesencephalon (VM). Inhibition of dopaminergic neurite growth induced by treatment of rat VM neurons with the dopaminergic neurotoxin 6- hydroxydopamine (6-OHDA) is mediated by p38, and is concomitant with a significant and selective decrease in MKP-1 expression in these neurons. Dopaminergic neurons transfected to overexpress MKP-1 displayed a more complex morphology and contributed to neuroprotection against the effects of 6-OHDA. Therefore, MKP-1 expression can promote the growth and elaboration of dopaminergic neuronal processes and can help protect them from the neurotoxic effects of 6-OHDA. Neural precursor cells (NPCs) have emerged as promising alternative candidates to fetal VM for cell replacement strategies in PD. Here we show that phosphorylated (and thus activated) p38 and MKP-1 are expressed at basal levels in untreated E14 rat VM NPCs (nestin, DCX, GFAP and DAT-positive cells) following proliferation as well as in their differentiated progeny (DCX, DAT, GFAP and βIII-tubulin) in vitro. Challenge with 6-OHDA or IL-1β changed the expression of endogenous phospho-p38 and MKP-1 in these cells in a time-dependent manner, and so the dynamic balance in expression may mediate the detrimental effects of neurotoxicity and inflammation in proliferating and differentiating NPCs. We demonstrate that there was an up-regulation in MKP-1 mRNA expression in adult rat midbrain tissue 4 days post lesion in two rat models of PD; the 6-OHDA medial forebrain bundle (MFB) model and the four-site 6-OHDA striatal lesion model. This was concomitant with a decrease in tyrosine hydroxylase (TH) mRNA expression at 4 and 10 days post-lesion in the MFB model and 10 and 28 days post-lesion in the striatal lesion model. There was no change in mRNA expression of the pro-apoptotic gene, bax and the anti-apoptotic gene, bcl-2 in the midbrain and striatum. These data suggest that the early and transient upregulation of MKP-1 mRNA in the midbrain at 4 days post-6-OHDA administration may be indicative of an attempt by dopaminergic neurons in the midbrain to protect against the neurotoxic effects of 6-OHDA at later time points. Collectively, these findings show that MKP-1 is expressed by developing and adult dopaminergic neurons in the midbrain, and can promote their morphological development. MKP-1 also exerts neuroprotective effects against dopaminergic neurotoxins in vitro, and its expression in dopaminergic neurons can be modulated by inflammatory and neurotoxic insults both in vitro and in vivo. Thus, these data contribute to the information needed to develop therapeutic strategies for protecting midbrain dopaminergic neurons in the context of PD.

Trophic role of small cetaceans and seals in Irish waters

Understanding the role of marine mammals in specific ecosystems and their interactions with fisheries involves, inter alia, an understanding of their diet and dietary requirements. In this thesis, the foraging ecology of seven marine mammal species that regularly occur in Irish waters was investigated by reconstructing diet using hard parts from digestive tracts and scats. Of the species examined, two (striped and Atlantic white-sided dolphin) can be considered offshore species or species inhabiting neritic waters, while five others usually inhabit more coastal areas (white-beaked dolphin, harbour porpoise, harbour seal and grey seal); the last species studied was the bottlenose dolphin whose population structure is more complex, with coastal and offshore populations. A total of 13,028 prey items from at least 81 different species (62 fish species, 14 cephalopods, four crustaceans, and a tunicate) were identified. 28% of the fish species were identified using bones other than otoliths, highlighting the importance of using all identifiable structures to reconstruct diet. Individually, each species of marine mammal presented a high diversity of prey taxa, but the locally abundant Trisopterus spp. were found to be the most important prey item for all species, indicating that Trisopterus spp. is probably a key species in understanding the role of these predators in Irish waters. In the coastal marine mammals, other Gadiformes species (haddock, pollack, saithe, whiting) also contributed substantially to the diet; in contrast, in pelagic or less coastal marine mammals, prey was largely comprised of planktivorous fish, such as Atlantic mackerel, horse mackerel, blue whiting, and mesopelagic prey. Striped dolphins and Atlantic white-sided dolphins are offshore small cetaceans foraging in neritic waters. Differences between the diet of striped dolphins collected in drift nets targeting tuna and stranded on Irish coasts showed a complex foraging behaviour; the diet information shows that although this dolphin forages mainly in oceanic waters it may occasionally forage on the continental shelf, feeding on available prey. The Atlantic white-sided dolphin diet showed that this species prefers to feed over the continental edge, where planktivorous fish are abundant. Some resource partitioning was found in bottlenose dolphins in Irish waters consistent with previous genetic and stable isotope analysis studies. Bottlenose dolphins in Irish waters appears to be generalist feeders consuming more than 30 prey species, however most of the diet comprised a few locally abundant species, especially gadoid fish including haddock/pollack/saithe group and Trisopterus spp., but the contribution of Atlantic hake, conger eels and the pelagic planktivorous horse mackerel were also important. Stomach content information suggests that three different feeding behaviours might occur in bottlenose dolphin populations in Irish waters; firstly a coastal behaviour, with animals feeding on prey that mainly inhabit areas close to the coast; secondly an offshore behaviour where dolphins feed on offshore species such as squid or mesopelagic fish; and a third more complex behaviour that involves movements over the continental shelf and close to the shelf edge. The other three coastal marine mammal species (harbour porpoise, harbour seal and grey seal) were found to be feeding on similar prey and competition for food resources among these sympatric species might occur. Both species of seals were found to have a high overlap (more than 80%) in their diet composition, but while grey seals feed on large fish (>110mm), harbour seals feed mostly on smaller fish (<110mm), suggesting some spatial segregation in foraging. Harbour porpoises and grey seals are potentially competing for the same food resource but some differences in prey species were found and some habitat partitioning might occur. Direct interaction (by catch) between dolphins and fisheries was detected in all species. Most of the prey found in the stomach contents from both stranded and by catch dolphins were smaller sizes than those targeted by commercial fisheries. In fact, the total annual food consumption of the species studied was found to be very small (225,160 tonnes) in comparison to fishery landings for the same area (~2 million tonnes). However, marine mammal species might be indirectly interacting with fisheries, removing forage fish. Incorporating the dietary information obtained from the four coastal species, an ECOPATH food web model was established for the Irish Sea, based on data from 2004. Five trophic levels were found, with bottlenose dolphins and grey and harbour seals occurring at the highest trophic level. A comparison with a previous model based on 1973 data suggests that while the overall Irish Sea ecosystem appears to be “maturing”, some indices indicate that the 2004 fishery was less efficient and was targeting fish at higher trophic levels than in 1973, which is reflected in the mean trophic level of the catch. Depletion or substantial decrease of some of the Irish Sea fish stocks has resulted in a significant decline in landings in this area. The integration of diet information in mass-balance models to construct ecosystem food-webs will help to understand the trophic role of these apex predators within the ecosystem.

Plasmonic gold nanostructures: optical properties and application in mercury detection

This thesis investigates the application of plasmonic gold nanostructures for mercury detection. Various gold and silver single nanostructures and gold nanostructure assemblies were characterised in detail by correlated single nanostructure spectroscopy and electron microscopy. Several routes for mercury detection were explored: plasmon resonance energy transfer (PRET) upon Hg2+ binding to immobilised gold nanoparticle-organic ligand hybrid structures and amalgamation of single immobilised gold nanorods upon chemical and upon electrochemical reduction of Hg2+ ions. The amalgamation approach showed large potential with extraordinary shifts of the nanorods’ scattering spectra upon exposure to reduced mercury; a result of compositional and morphological change induced in the nanorod by amalgamation with mercury. A shift of 5 nm could be recorded for a concentration as low 10 nM Hg2+. Through detailed time-dependent experiments insights into the amalgamation mechanism were gained and a model comprising 5 steps was developed. Finally, spectroelectrochemistry proved to be an excellent way to study in real time in-situ the amalgamation of mercury with gold nanorods paving the way for future work in this field.

Researcher practices on returning genetic research results.

BACKGROUND/AIMS: as genetic and genomic research proliferates, debate has ensued about returning results to participants. In addition to consideration of the benefits and harms to participants, researchers must also consider the logistical and financial feasibility of returning research results. However, little data exist of actual researcher practices. METHODS: we conducted an online survey of 446 corresponding authors of genetic/genomic studies conducted in the United States and published in 2006-2007 to assess the frequency with which they considered, offered to, or actually returned research results, what factors influenced these decisions, and the method of communicating results. RESULTS: the response rate was 24% (105/446). Fifty-four percent of respondents considered the issue of returning research results to participants, 28% offered to return individual research results, and 24% actually returned individual research results. Of those who considered the issue of returning research results during the study planning phase, the most common factors considered were whether research results were deemed clinically useful (18%) and respect for participants (13%). Researchers who had a medical degree and conducted studies on children were significantly more likely to offer to return or actually return individual results compared to those with a Ph.D. only. CONCLUSIONS: we speculate that issues associated with clinical validity and respect for participants dominated concerns of time and expense given the prominent and continuing ethical debates surrounding genetics and genomics research. The substantial number of researchers who did not consider returning research results suggests that researchers and institutional review boards need to devote more attention to a topic about which research participants are interested.

Independent evolutionary origins of landlocked alewife populations and rapid parallel evolution of phenotypic traits.

Alewife, Alosa pseudoharengus, populations occur in two discrete life-history variants, an anadromous form and a landlocked (freshwater resident) form. Landlocked populations display a consistent pattern of life-history divergence from anadromous populations, including earlier age at maturity, smaller adult body size, and reduced fecundity. In Connecticut (USA), dams constructed on coastal streams separate anadromous spawning runs from lake-resident landlocked populations. Here, we used sequence data from the mtDNA control region and allele frequency data from five microsatellite loci to ask whether coastal Connecticut landlocked alewife populations are independently evolved from anadromous populations or whether they share a common freshwater ancestor. We then used microsatellite data to estimate the timing of the divergence between anadromous and landlocked populations. Finally, we examined anadromous and landlocked populations for divergence in foraging morphology and used divergence time estimates to calculate the rate of evolution for foraging traits. Our results indicate that landlocked populations have evolved multiple times independently. Tests of population divergence and estimates of gene flow show that landlocked populations are genetically isolated, whereas anadromous populations exchange genes. These results support a 'phylogenetic raceme' model of landlocked alewife divergence, with anadromous populations forming an ancestral core from which landlocked populations independently diverged. Divergence time estimates suggest that landlocked populations diverged from a common anadromous ancestor no longer than 5000 years ago and perhaps as recently as 300 years ago, depending on the microsatellite mutation rate assumed. Examination of foraging traits reveals landlocked populations to have significantly narrower gapes and smaller gill raker spacings than anadromous populations, suggesting that they are adapted to foraging on smaller prey items. Estimates of evolutionary rates (in haldanes) indicate rapid evolution of foraging traits, possibly in response to changes in available resources.

Harm, hype and evidence: ELSI research and policy guidance.

There has been much investment in research on the ethical, legal and social issues (ELSI) associated with genetic and genomic research. This research should inform the development of the relevant policy. So far, much of the relevant policy - such as in the areas of patents, genetic testing and genetic discrimination - seems to be informed more by speculation of harm and anecdote than by available evidence. Although a quest for evidence cannot always be allowed to delay policy choice, it seems axiomatic to us that policy options are improved by the incorporation of evidence.

Outer Membrane Vesicle Production in Escherichia coli Relieves Envelope Stress and is Modulated by Changes in Peptidoglycan

Bacterial outer membrane vesicles (OMVs) are spherical buds of the outer membrane (OM) containing periplasmic lumenal components. OMVs have been demonstrated to play a critical part in the transmission of virulence factors, immunologically active compounds, and bacterial survival, however vesiculation also appears to be a ubiquitous physiological process for Gram-negative bacteria. Despite their characterized biological roles, especially for pathogens, very little is known about their importance for the originating organism as well as regulation and mechanism of production. Only when we have established their biogenesis can we fully uncover their roles in pathogenesis and bacterial physiology. The overall goal of this research was to characterize bacterial mutants which display altered vesiculation phenotypes using genetic and biochemical techniques, and thereby begin to elucidate the mechanism of vesicle production and regulation. One part of this work elucidated a synthetic genetic growth defect for a strain with reduced OMV production (ΔnlpA, inner membrane lipoprotein with a minor role in methionine transport) and envelope stress (ΔdegP, dual function periplasmic chaperone/ protease responsible for managing proteinaceous waste). This research showed that the growth defect of ΔnlpAΔdegP correlated with reduced OMV production with respect to the hyprevesiculator ΔdegP and the accumulation of protein in the periplasm and DegP substrates in the lumen of OMVs. We further demonstrated that OMVs do not solely act as a stress response pathway to rid the periplasm of otherwise damaging misfolded protein but also of accumulated peptidoglycan (PG) fragments and lipopolysaccharide (LPS), elucidating OMVs as a general stress response pathway critical for bacterial well-being. The second part of this work, focused on the role of PG structure, turnover and covalent crosslinks to the OM in vesiculation. We established a direct link between PG degradation and vesiculation: Mutations in the OM lipoprotein nlpI had been previously established as a very strong hypervesiculation phenotype. In the literature NlpI had been associated with another OM lipoprotein, Spr that was recently identified as a PG hydrolase. The data presented here suggest that NlpI acts as a negative regulator of Spr and that the ΔnlpI hypervesiculation phenotype is a result of rampantly degraded PG by Spr. Additionally, we found that changes in PG structure and turnover correlate with altered vesiculation levels, as well as non-canonical D-amino acids, which are secreted by numerous bacteria on the onset of stationary phase, being a natural factor to increase OMV production. Furthermore, we discovered an inverse relationship between the concentration of Lpp-mediated, covalent crosslinks and the level of OMV production under conditions of modulated PG metabolism and structure. In contrast, situations that lead to periplasmic accumulation (protein, PG fragments, and LPS) and consequent hypervesiculation the overall OM-PG crosslink concentration appears to be unchanged. Form this work, we conclude that multiple pathways lead to OMV production: Lpp concentration-dependent and bulk driven, Lpp concentration-independent.

Nucleolar organization, ribosomal DNA array stability, and acrocentric chromosome integrity are linked to telomere function.

The short arms of the ten acrocentric human chromosomes share several repetitive DNAs, including ribosomal RNA genes (rDNA). The rDNA arrays correspond to nucleolar organizing regions that coalesce each cell cycle to form the nucleolus. Telomere disruption by expressing a mutant version of telomere binding protein TRF2 (dnTRF2) causes non-random acrocentric fusions, as well as large-scale nucleolar defects. The mechanisms responsible for acrocentric chromosome sensitivity to dysfunctional telomeres are unclear. In this study, we show that TRF2 normally associates with the nucleolus and rDNA. However, when telomeres are crippled by dnTRF2 or RNAi knockdown of TRF2, gross nucleolar and chromosomal changes occur. We used the controllable dnTRF2 system to precisely dissect the timing and progression of nucleolar and chromosomal instability induced by telomere dysfunction, demonstrating that nucleolar changes precede the DNA damage and morphological changes that occur at acrocentric short arms. The rDNA repeat arrays on the short arms decondense, and are coated by RNA polymerase I transcription binding factor UBF, physically linking acrocentrics to one another as they become fusogenic. These results highlight the importance of telomere function in nucleolar stability and structural integrity of acrocentric chromosomes, particularly the rDNA arrays. Telomeric stress is widely accepted to cause DNA damage at chromosome ends, but our findings suggest that it also disrupts chromosome structure beyond the telomere region, specifically within the rDNA arrays located on acrocentric chromosomes. These results have relevance for Robertsonian translocation formation in humans and mechanisms by which acrocentric-acrocentric fusions are promoted by DNA damage and repair.

The vertebrate taxonomy ontology: a framework for reasoning across model organism and species phenotypes.

BACKGROUND: A hierarchical taxonomy of organisms is a prerequisite for semantic integration of biodiversity data. Ideally, there would be a single, expansive, authoritative taxonomy that includes extinct and extant taxa, information on synonyms and common names, and monophyletic supraspecific taxa that reflect our current understanding of phylogenetic relationships. DESCRIPTION: As a step towards development of such a resource, and to enable large-scale integration of phenotypic data across vertebrates, we created the Vertebrate Taxonomy Ontology (VTO), a semantically defined taxonomic resource derived from the integration of existing taxonomic compilations, and freely distributed under a Creative Commons Zero (CC0) public domain waiver. The VTO includes both extant and extinct vertebrates and currently contains 106,947 taxonomic terms, 22 taxonomic ranks, 104,736 synonyms, and 162,400 cross-references to other taxonomic resources. Key challenges in constructing the VTO included (1) extracting and merging names, synonyms, and identifiers from heterogeneous sources; (2) structuring hierarchies of terms based on evolutionary relationships and the principle of monophyly; and (3) automating this process as much as possible to accommodate updates in source taxonomies. CONCLUSIONS: The VTO is the primary source of taxonomic information used by the Phenoscape Knowledgebase (http://phenoscape.org/), which integrates genetic and evolutionary phenotype data across both model and non-model vertebrates. The VTO is useful for inferring phenotypic changes on the vertebrate tree of life, which enables queries for candidate genes for various episodes in vertebrate evolution.

Biogeography in deep time - What do phylogenetics, geology, and paleoclimate tell us about early platyrrhine evolution?

Molecular data have converged on a consensus about the genus-level phylogeny of extant platyrrhine monkeys, but for most extinct taxa and certainly for those older than the Pleistocene we must rely upon morphological evidence from fossils. This raises the question as to how well anatomical data mirror molecular phylogenies and how best to deal with discrepancies between the molecular and morphological data as we seek to extend our phylogenies to the placement of fossil taxa. Here I present parsimony-based phylogenetic analyses of extant and fossil platyrrhines based on an anatomical dataset of 399 dental characters and osteological features of the cranium and postcranium. I sample 16 extant taxa (one from each platyrrhine genus) and 20 extinct taxa of platyrrhines. The tree structure is constrained with a "molecular scaffold" of extant species as implemented in maximum parsimony using PAUP with the molecular-based 'backbone' approach. The data set encompasses most of the known extinct species of platyrrhines, ranging in age from latest Oligocene (∼26 Ma) to the Recent. The tree is rooted with extant catarrhines, and Late Eocene and Early Oligocene African anthropoids. Among the more interesting patterns to emerge are: (1) known early platyrrhines from the Late Oligocene through Early Miocene (26-16.5Ma) represent only stem platyrrhine taxa; (2) representatives of the three living platyrrhine families first occur between 15.7 Ma and 13.5 Ma; and (3) recently extinct primates from the Greater Antilles (Cuba, Jamaica, Hispaniola) are sister to the clade of extant platyrrhines and may have diverged in the Early Miocene. It is probable that the crown platyrrhine clade did not originate before about 20-24 Ma, a conclusion consistent with the phylogenetic analysis of fossil taxa presented here and with recent molecular clock estimates. The following biogeographic scenario is consistent with the phylogenetic findings and climatic and geologic evidence: Tropical South America has been a center for platyrrhine diversification since platyrrhines arrived on the continent in the middle Cenozoic. Platyrrhines dispersed from tropical South America to Patagonia at ∼25-24 Ma via a "Paraná Portal" through eastern South America across a retreating Paranense Sea. Phylogenetic bracketing suggests Antillean primates arrived via a sweepstakes route or island chain from northern South America in the Early Miocene, not via a proposed land bridge or island chain (GAARlandia) in the Early Oligocene (∼34 Ma). Patagonian and Antillean platyrrhines went extinct without leaving living descendants, the former at the end of the Early Miocene and the latter within the past six thousand years. Molecular evidence suggests crown platyrrhines arrived in Central America by crossing an intermittent connection through the Isthmus of Panama at or after 3.5Ma. Any more ancient Central American primates, should they be discovered, are unlikely to have given rise to the extant Central American taxa in situ.

Incontinence and gait disturbance after intraventricular extension of intracerebral hemorrhage.

OBJECTIVE: We tested the hypothesis that intraventricular hemorrhage (IVH) is associated with incontinence and gait disturbance among survivors of intracerebral hemorrhage (ICH) at 3-month follow-ups. METHODS: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study was used as the discovery set. The Ethnic/Racial Variations of Intracerebral Hemorrhage study served as a replication set. Both studies performed prospective hot-pursuit recruitment of ICH cases with 3-month follow-up. Multivariable logistic regression analyses were computed to identify risk factors for incontinence and gait dysmobility at 3 months after ICH. RESULTS: The study population consisted of 307 ICH cases in the discovery set and 1,374 cases in the replication set. In the discovery set, we found that increasing IVH volume was associated with incontinence (odds ratio [OR] 1.50; 95% confidence interval [CI] 1.10-2.06) and dysmobility (OR 1.58; 95% CI 1.17-2.15) after controlling for ICH location, initial ICH volume, age, baseline modified Rankin Scale score, sex, and admission Glasgow Coma Scale score. In the replication set, increasing IVH volume was also associated with both incontinence (OR 1.42; 95% CI 1.27-1.60) and dysmobility (OR 1.40; 95% CI 1.24-1.57) after controlling for the same variables. CONCLUSION: ICH subjects with IVH extension are at an increased risk for developing incontinence and dysmobility after controlling for factors associated with severity and disability. This finding suggests a potential target to prevent or treat long-term disability after ICH with IVH.