115 research outputs found
Living With Maternal HIV: Spirituality, Depression, And Family Functioning
Risk factors such as depression and low SES often affect an HIV infected mother’s ability to function within her family. Spirituality may interact with such risk factors contributing to the resiliency of these mothers. The current study explored spirituality’s influence on the relationship between depression and perceptions of family functioning in African American women living with HIV. High levels of spirituality were associated with decreased psychological distress and spirituality served as a significant predictor of family cohesion. Findings from this study support the importance of spirituality in the lives of African American women living with HIV and their families
Engineering the Fab fragment of the anti-IgE omalizumab to prevent Fab crystallization and permit IgE-Fc complex crystallization
Immunoglobulin E (IgE) plays a central role in the allergic response, in which cross-linking of allergen by Fc[epsilon]RI-bound IgE triggers mast cell and basophil degranulation and the release of inflammatory mediators. The high-affinity interaction between IgE and Fc[epsilon]RI is a long-standing target for therapeutic intervention in allergic disease. Omalizumab is a clinically approved anti-IgE monoclonal antibody that binds to free IgE, also with high affinity, preventing its interaction with Fc[epsilon]RI. All attempts to crystallize the pre-formed complex between the omalizumab Fab and the Fc region of IgE (IgE-Fc), to understand the structural basis for its mechanism of action, surprisingly failed. Instead, the Fab alone selectively crystallized in different crystal forms, but their structures revealed intermolecular Fab/Fab interactions that were clearly strong enough to disrupt the Fab/IgE-Fc complexes. Some of these interactions were common to other Fab crystal structures. Mutations were therefore designed to disrupt two recurring packing interactions observed in the omalizumab Fab crystal structures without interfering with the ability of the omalizumab Fab to recognize IgE-Fc; this led to the successful crystallization and subsequent structure determination of the Fab/IgE-Fc complex. The mutagenesis strategy adopted to achieve this result is applicable to other intractable Fab/antigen complexes or systems in which Fabs are used as crystallization chaperones
Presidential Election Laws and Multipartism in Latin America
This article examines the interaction between the rules governing presidential elections and multipartism in Latin America. Data from 16 Latin American systems are examined through the use of a multivariate model to gain an understanding of the independent impact of presidential electoral formula (plurality vs. majority), the timing of presidential and legislative elections (concurrent vs. nonconcurrent) and legislative district magnitude on legislative multipartism, and by extension, on the number of relevant political parties operating in the nation. The findings demonstrate the strong and significant impact which formula and timing have on multipartism. They also point to the importance of examining the interaction between elections for different constituent institutions. Finally, they underscore the applicability of Duverger's law to presidential elections.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68710/2/10.1177_106591299404700103.pd
The Effect of Inappropriate Calibration: Three Case Studies in Molecular Ecology
Time-scales estimated from sequence data play an important role in molecular ecology. They can be used to draw correlations between evolutionary and palaeoclimatic events, to measure the tempo of speciation, and to study the demographic history of an endangered species. In all of these studies, it is paramount to have accurate estimates of time-scales and substitution rates. Molecular ecological studies typically focus on intraspecific data that have evolved on genealogical scales, but often these studies inappropriately employ deep fossil calibrations or canonical substitution rates (e.g., 1% per million years for birds and mammals) for calibrating estimates of divergence times. These approaches can yield misleading estimates of molecular time-scales, with significant impacts on subsequent evolutionary and ecological inferences. We illustrate this calibration problem using three case studies: avian speciation in the late Pleistocene, the demographic history of bowhead whales, and the Pleistocene biogeography of brown bears. For each data set, we compare the date estimates that are obtained using internal and external calibration points. In all three cases, the conclusions are significantly altered by the application of revised, internally-calibrated substitution rates. Collectively, the results emphasise the importance of judicious selection of calibrations for analyses of recent evolutionary events
Time-calibrated phylogenetic trees establish a lag between polyploidisation and diversification in Nicotiana (Solanaceae)
We investigate the timing of diversification in allopolyploids of Nicotiana (Solanaceae) utilising sequence data of maternal and paternal origin to look for evidence of a lag phase during which diploidisation took place. Bayesian relaxed clock phylogenetic methods show recent allopolyploids are a result of several unique polyploidisation events, and older allopolyploid sections have undergone subsequent speciation at the polyploid level (i.e. a number of these polyploid species share a singular origin). The independently formed recent polyploid species in the genus all have mean age estimates below 1 million years ago (Ma). Nicotiana section Polydicliae (two species) evolved 1.5 Ma, N. section Repandae (four species) formed 4 Ma, and N. section Suaveolentes (*35 species) is about 6 million years old. A general trend of higher speciation rates in older polyploids is evident, but diversification dramatically increases at approximately 6 Ma (in section Suaveolentes). Nicotiana sect. Suaveolentes has spectacularly radiated to form 35 species in Australia and some Pacific islands following a lag phase of almost 6 million years. Species have filled new ecological niches and undergone extensive diploidisation (e.g. chromosome fusions bringing the ancestral allotetraploid number, n = 24, down to n = 15 and ribosomal loci numbers back to diploid condition). Considering the progenitors of Suaveolentes inhabit South America, this represents the colonisation of Australia by polyploids that have subsequently undergone a recent radiation into new environments. To our knowledge, this study is the first report of a substantial lag phase being investigated below the family level
Expression and regulation of type 2A protein phosphatases and alpha4 signalling in cardiac health and hypertrophy
Abstract Cardiac physiology and hypertrophy are regulated
by the phosphorylation status of many proteins, which
is partly controlled by a poorly defined type 2A protein
phosphatase-alpha4 intracellular signalling axis. Quantitative
PCR analysis revealed that mRNA levels of the type
2A catalytic subunits were differentially expressed in H9c2
cardiomyocytes (PP2ACb[PP2ACa[PP4C[PP6C),
NRVM (PP2ACb[PP2ACa = PP4C = PP6C), and
adult rat ventricular myocytes (PP2ACa[
PP2ACb[PP6C[PP4C). Western analysis confirmed
that all type 2A catalytic subunits were expressed in H9c2
cardiomyocytes; however, PP4C protein was absent in
adult myocytes and only detectable following 26S proteasome
inhibition. Short-term knockdown of alpha4 protein
expression attenuated expression of all type 2A catalytic
subunits. Pressure overload-induced left ventricular (LV)
hypertrophy was associated with an increase in both
PP2AC and alpha4 protein expression. Although PP6C
expression was unchanged, expression of PP6C regulatory
subunits (1) Sit4-associated protein 1 (SAP1) and (2)
ankyrin repeat domain (ANKRD) 28 and 44 proteins was
elevated, whereas SAP2 expression was reduced in
hypertrophied LV tissue. Co-immunoprecipitation studies
demonstrated that the interaction between alpha4 and
PP2AC or PP6C subunits was either unchanged or reduced
in hypertrophied LV tissue, respectively. Phosphorylation
status of phospholemman (Ser63 and Ser68) was significantly
increased by knockdown of PP2ACa, PP2ACb, or
PP4C protein expression. DNA damage assessed by histone
H2A.X phosphorylation (cH2A.X) in hypertrophied tissue
remained unchanged. However, exposure of cardiomyocytes
to H2O2 increased levels of cH2A.X which was
unaffected by knockdown of PP6C expression, but was
abolished by the short-term knockdown of alpha4 expression.
This study illustrates the significance and altered
activity of the type 2A protein phosphatase-alpha4 complex
in healthy and hypertrophied myocardium
In Vivo Imaging Reveals Distinct Inflammatory Activity of CNS Microglia versus PNS Macrophages in a Mouse Model for ALS
Mutations in the enzyme superoxide dismutase-1 (SOD1) cause hereditary variants
of the fatal motor neuronal disease Amyotrophic lateral sclerosis (ALS).
Pathophysiology of the disease is non-cell-autonomous: neurotoxicity is derived
not only from mutant motor neurons but also from mutant neighbouring
non-neuronal cells. In vivo imaging by two-photon
laser-scanning microscopy was used to compare the role of
microglia/macrophage-related neuroinflammation in the CNS and PNS using
ALS-linked transgenic SOD1G93A mice. These mice contained labeled
projection neurons and labeled microglia/macrophages. In the affected lateral
spinal cord (in contrast to non-affected dorsal columns), different phases of
microglia-mediated inflammation were observed: highly reactive microglial cells
in preclinical stages (in 60-day-old mice the reaction to axonal transection was
∼180% of control) and morphologically transformed microglia that have
lost their function of tissue surveillance and injury-directed response in
clinical stages (reaction to axonal transection was lower than 50% of
control). Furthermore, unlike CNS microglia, macrophages of the PNS lack any
substantial morphological reaction while preclinical degeneration of peripheral
motor axons and neuromuscular junctions was observed. We present in
vivo evidence for a different inflammatory activity of microglia
and macrophages: an aberrant neuroinflammatory response of microglia in the CNS
and an apparently mainly neurodegenerative process in the PNS
The Biodiversity of the Mediterranean Sea: Estimates, Patterns, and Threats
The Mediterranean Sea is a marine biodiversity hot spot. Here we combined an extensive literature analysis with expert opinions to update publicly available estimates of major taxa in this marine ecosystem and to revise and update several species lists. We also assessed overall spatial and temporal patterns of species diversity and identified major changes and threats. Our results listed approximately 17,000 marine species occurring in the Mediterranean Sea. However, our estimates of marine diversity are still incomplete as yet—undescribed species will be added in the future. Diversity for microbes is substantially underestimated, and the deep-sea areas and portions of the southern and eastern region are still poorly known. In addition, the invasion of alien species is a crucial factor that will continue to change the biodiversity of the Mediterranean, mainly in its eastern basin that can spread rapidly northwards and westwards due to the warming of the Mediterranean Sea. Spatial patterns showed a general decrease in biodiversity from northwestern to southeastern regions following a gradient of production, with some exceptions and caution due to gaps in our knowledge of the biota along the southern and eastern rims. Biodiversity was also generally higher in coastal areas and continental shelves, and decreases with depth. Temporal trends indicated that overexploitation and habitat loss have been the main human drivers of historical changes in biodiversity. At present, habitat loss and degradation, followed by fishing impacts, pollution, climate change, eutrophication, and the establishment of alien species are the most important threats and affect the greatest number of taxonomic groups. All these impacts are expected to grow in importance in the future, especially climate change and habitat degradation. The spatial identification of hot spots highlighted the ecological importance of most of the western Mediterranean shelves (and in particular, the Strait of Gibraltar and the adjacent Alboran Sea), western African coast, the Adriatic, and the Aegean Sea, which show high concentrations of endangered, threatened, or vulnerable species. The Levantine Basin, severely impacted by the invasion of species, is endangered as well
Evolutionary diversification of new caledonian Araucaria
New Caledonia is a global biodiversity hotspot. Hypotheses for its biotic richness suggest either that the island is a ‘museum’ for an old Gondwana biota or alternatively it has developed following relatively recent long distance dispersal and in situ radiation. The conifer genus Araucaria (Araucariaceae) comprises 19 species globally with 13 endemic to this island. With a typically Gondwanan distribution, Araucaria is particularly well suited to testing alternative biogeographic hypotheses concerning the origins of New Caledonian biota. We derived phylogenetic estimates using 11 plastid and rDNA ITS2 sequence data for a complete sampling of Araucaria (including multiple accessions of each of the 13 New Caledonian Araucaria species). In addition, we developed a dataset comprising 4 plastid regions for a wider taxon sample to facilitate fossil based molecular dating. Following statistical analyses to identify a credible and internally consistent set of fossil constraints, divergence times estimated using a Bayesian relaxed clock approach were contrasted with geological scenarios to explore the biogeographic history of Araucaria. The phylogenetic data resolve relationships within Araucariaceae and among the main lineages in Araucaria, but provide limited resolution within the monophyletic New Caledonian species group. Divergence time estimates suggest a Late Cretaceous-Cenozoic radiation of extant Araucaria and a Neogene radiation of the New Caledonian lineage. A molecular timescale for the evolution of Araucariaceae supports a relatively recent radiation, and suggests that earlier (pre-Cenozoic) fossil types assigned to Araucaria may have affinities elsewhere in Araucariaceae. While additional data will be required to adequately resolve relationships among the New Caledonian species, their recent origin is consistent with overwater dispersal following Eocene emersion of New Caledonia but is too old to support a single dispersal from Australia to Norfolk Island for the radiation of the Pacific Araucaria sect. Eutacta clade.Mai Lan Kranitz, Edward Biffin, Alexandra Clark, Michelle L. Hollingsworth, Markus Ruhsam, Martin F. Gardner, Philip Thomas, Robert R. Mill, Richard A. Ennos, Myriam Gaudeul, Andrew J. Lowe, Peter M. Hollingswort
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