Browsing by Subject "multidisciplinary sciences"

Now showing 1 - 13 of 13
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    A Comparison of the Wellbeing of Orphans and Abandoned Children Ages 6-12 in Institutional and Community-Based Care Settings in 5 Less Wealthy Nations
    (2009) Whetten, Kathryn; Ostermann, Jan; Whetten, Rachel A; Pence, Brian W; O'Donnell, Karen; Messer, Lynne C; Thielman, Nathan M; Positive Outcomes for Orphans (POFO) Research Team
    Background: Leaders are struggling to care for the estimated 143,000,000 orphans and millions more abandoned children worldwide. Global policy makers are advocating that institution-living orphans and abandoned children (OAC) be moved as quickly as possible to a residential family setting and that institutional care be used as a last resort. This analysis tests the hypothesis that institutional care for OAC aged 6-12 is associated with worse health and wellbeing than community residential care using conservative two-tail tests. Methodology: The Positive Outcomes for Orphans (POFO) study employed two-stage random sampling survey methodology in 6 sites across 5 countries to identify 1,357 institution-living and 1,480 community-living OAC ages 6-12, 658 of whom were double-orphans or abandoned by both biological parents. Survey analytic techniques were used to compare cognitive functioning, emotion, behavior, physical health, and growth. Linear mixed-effects models were used to estimate the proportion of variability in child outcomes attributable to the study site, care setting, and child levels and institutional versus community care settings. Conservative analyses limited the community living children to double-orphans or abandoned children. Principal Findings: Health, emotional and cognitive functioning, and physical growth were no worse for institution-living than community-living OAC, and generally better than for community-living OAC cared for by persons other than a biological parent. Differences between study sites explained 2-23% of the total variability in child outcomes, while differences between care settings within sites explained 8-21%. Differences among children within care settings explained 64-87%. After adjusting for sites, age, and gender, institution vs. community-living explained only 0.3-7% of the variability in child outcomes. Conclusion: This study does not support the hypothesis that institutional care is systematically associated with poorer wellbeing than community care for OAC aged 6-12 in those countries facing the greatest OAC burden. Much greater variability among children within care settings was observed than among care settings type. Methodologically rigorous studies must be conducted in those countries facing the new OAC epidemic in order to understand which characteristics of care promote child wellbeing. Such characteristics may transcend the structural definitions of institutions or family homes.
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    Climate Change and the Future of California's Endemic Flora
    (2008) Loarie, Scott R; Carter, Benjamin E; Hayhoe, Katharine; McMahon, Sean; Moe, Richard; Knight, Charles A; Ackerly, David D
    The flora of California, a global biodiversity hotspot, includes 2387 endemic plant taxa. With anticipated climate change, we project that up to 66% will experience >80% reductions in range size within a century. These results are comparable with other studies of fewer species or just samples of a region's endemics. Projected reductions depend on the magnitude of future emissions and on the ability of species to disperse from their current locations. California's varied terrain could cause species to move in very different directions, breaking up present-day floras. However, our projections also identify regions where species undergoing severe range reductions may persist. Protecting these potential future refugia and facilitating species dispersal will be essential to maintain biodiversity in the face of climate change.
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    Dynamic Properties of Coupled Maps
    (2010) Zhang, C; Zheng, H
    Dynamic properties are investigated in the coupled system of three maps with symmetric nearest neighbor coupling and periodic boundary conditions. The dynamics of the system is controlled by certain coupling parameters. We show that, for some values of the parameters, the system exhibits nontrivial collective behavior, such as multiple bifurcations, and chaos. We give computer simulations to support the theoretical predictions.
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    Evolutionary Genomics Reveals Lineage-Specific Gene Loss and Rapid Evolution of a Sperm-Specific Ion Channel Complex: CatSpers and CatSper beta
    (2008) Cai, Xinjiang; Clapham, David E
    The mammalian CatSper ion channel family consists of four sperm-specific voltage-gated Ca2+ channels that are crucial for sperm hyperactivation and male fertility. All four CatSper subunits are believed to assemble into a heteromultimeric channel complex, together with an auxiliary subunit, CatSperb. Here, we report a comprehensive comparative genomics study and evolutionary analysis of CatSpers and CatSperb, with important correlation to physiological significance of molecular evolution of the CatSper channel complex. The development of the CatSper channel complex with four CatSpers and CatSperb originated as early as primitive metazoans such as the Cnidarian Nematostella vectensis. Comparative genomics revealed extensive lineage-specific gene loss of all four CatSpers and CatSperb through metazoan evolution, especially in vertebrates. The CatSper channel complex underwent rapid evolution and functional divergence, while distinct evolutionary constraints appear to have acted on different domains and specific sites of the four CatSper genes. These results reveal unique evolutionary characteristics of sperm-specific Ca2+ channels and their adaptation to sperm biology through metazoan evolution.
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    Favorable Climate Change Response Explains Non-Native Species' Success in Thoreau's Woods
    (2010) Willis, Charles G; Ruhfel, Brad R; Primack, Richard B; Miller-Rushing, Abraham J; Losos, Jonathan B; Davis, Charles C
    Invasive species have tremendous detrimental ecological and economic impacts. Climate change may exacerbate species invasions across communities if non-native species are better able to respond to climate changes than native species. Recent evidence indicates that species that respond to climate change by adjusting their phenology (i.e., the timing of seasonal activities, such as flowering) have historically increased in abundance. The extent to which non-native species success is similarly linked to a favorable climate change response, however, remains untested. We analyzed a dataset initiated by the conservationist Henry David Thoreau that documents the long-term phenological response of native and non-native plant species over the last 150 years from Concord, Massachusetts (USA). Our results demonstrate that non-native species, and invasive species in particular, have been far better able to respond to recent climate change by adjusting their flowering time. This demonstrates that climate change has likely played, and may continue to play, an important role in facilitating non-native species naturalization and invasion at the community level.
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    Fluorescent Labeling of Newborn Dentate Granule Cells in GAD67-GFP Transgenic Mice: A Genetic Tool for the Study of Adult Neurogenesis
    (2010) Zhao, Shengli; Zhou, Yang; Gross, Jimmy; Miao, Pei; Qiu, Li; Wang, Dongqing; Chen, Qian; Feng, Guoping
    Neurogenesis in the adult hippocampus is an important form of structural plasticity in the brain. Here we report a line of BAC transgenic mice (GAD67-GFP mice) that selectively and transitorily express GFP in newborn dentate granule cells of the adult hippocampus. These GFP+ cells show a high degree of colocalization with BrdU-labeled nuclei one week after BrdU injection and express the newborn neuron marker doublecortin and PSA-NCAM. Compared to mature dentate granule cells, these newborn neurons show immature morphological features: dendritic beading, fewer dendritic branches and spines. These GFP+ newborn neurons also show immature electrophysiological properties: higher input resistance, more depolarized resting membrane potentials, small and non-typical action potentials. The bright labeling of newborn neurons with GFP makes it possible to visualize the details of dendrites, which reach the outer edge of the molecular layer, and their axon (mossy fiber) terminals, which project to the CA3 region where they form synaptic boutons. GFP expression covers the whole developmental stage of newborn neurons, beginning within the first week of cell division and disappearing as newborn neurons mature, about 4 weeks postmitotic. Thus, the GAD67-GFP transgenic mice provide a useful genetic tool for studying the development and regulation of newborn dentate granule cells.
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    Global Conservation Significance of Ecuador's Yasuni National Park
    (2010) Bass, Margot S; Finer, Matt; Jenkins, Clinton N; Kreft, Holger; Cisneros-Heredia, Diego F; McCracken, Shawn F; Pitman, Nigel CA; English, Peter H; Swing, Kelly; Villa, Gorky; Di Fiore, Anthony; Voigt, Christian C; Kunz, Thomas H
    Background: The threats facing Ecuador's Yasuni National Park are emblematic of those confronting the greater western Amazon, one of the world's last high-biodiversity wilderness areas. Notably, the country's second largest untapped oil reserves-called "ITT''-lie beneath an intact, remote section of the park. The conservation significance of Yasuni may weigh heavily in upcoming state-level and international decisions, including whether to develop the oil or invest in alternatives. Methodology/Principal Findings: We conducted the first comprehensive synthesis of biodiversity data for Yasuni. Mapping amphibian, bird, mammal, and plant distributions, we found eastern Ecuador and northern Peru to be the only regions in South America where species richness centers for all four taxonomic groups overlap. This quadruple richness center has only one viable strict protected area (IUCN levels I-IV): Yasuni. The park covers just 14% of the quadruple richness center's area, whereas active or proposed oil concessions cover 79%. Using field inventory data, we compared Yasuni's local (alpha) and landscape (gamma) diversity to other sites, in the western Amazon and globally. These analyses further suggest that Yasuni is among the most biodiverse places on Earth, with apparent world richness records for amphibians, reptiles, bats, and trees. Yasuni also protects a considerable number of threatened species and regional endemics. Conclusions/Significance: Yasuni has outstanding global conservation significance due to its extraordinary biodiversity and potential to sustain this biodiversity in the long term because of its 1) large size and wilderness character, 2) intact large-vertebrate assemblage, 3) IUCN level-II protection status in a region lacking other strict protected areas, and 4) likelihood of maintaining wet, rainforest conditions while anticipated climate change-induced drought intensifies in the eastern Amazon. However, further oil development in Yasuni jeopardizes its conservation values. These findings form the scientific basis for policy recommendations, including stopping any new oil activities and road construction in Yasuni and creating areas off-limits to large-scale development in adjacent northern Peru.
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    Land Use, Macroalgae, and a Tumor-Forming Disease in Marine Turtles
    (2010) Van Houtan, Kyle S; Hargrove, Stacy K; Balazs, George H
    Wildlife diseases are an increasing concern for endangered species conservation, but their occurrence, causes, and human influences are often unknown. We analyzed 3,939 records of stranded Hawaiian green sea turtles (Chelonia mydas) over 28 years to understand fibropapillomatosis, a tumor-forming disease linked to a herpesvirus. Turtle size is a consistent risk factor and size-standardized models revealed considerable spatial and temporal variability. The disease peaked in some areas in the 1990s, in some regions rates remained constant, and elsewhere rates increased. Land use, onshore of where the turtles feed, may play a role. Elevated disease rates were clustered in watersheds with high nitrogen-footprints; an index of natural and anthropogenic factors that affect coastal eutrophication. Further analysis shows strong epidemiological links between disease rates, nitrogen-footprints, and invasive macroalgae and points to foraging ecology. These turtles now forage on invasive macroalgae, which can dominate nutrient rich waters and sequester environmental N in the amino acid arginine. Arginine is known to regulate immune activity, promote herpesviruses, and contribute to tumor formation. Our results have implications for understanding diseases in aquatic organisms, eutrophication, herpesviruses, and tumor formation.
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    Mono- or Double-Site Phosphorylation Distinctly Regulates the Proapoptotic Function of Bax
    (2010) Wang, Qinhong; Sun, Shi-Yong; Khuri, Fadlo; Curran, Walter J; Deng, Xingming
    Bax is the major multidomain proapoptotic molecule that is required for apoptosis. It has been reported that phosphorylation of Bax at serine(S) 163 or S184 activates or inactivates its proapoptotic function, respectively. To uncover the mechanism(s) by which phosphorylation regulates the proapoptotic function of Bax, a series of serine (S)-> alanine/glutamate (A/E) Bax mutants, including S163A, S184A, S163E, S184E, S163E/S184A (EA), S163A/S184E (AE), S163A/S184A (AA) and S163E/S184E (EE), were created to abrogate or mimic, respectively, either single or double-site phosphorylation. The compound Bax mutants (i.e. EA and AE) can flesh out the functional contribution of individual phosphorylation site(s). WT and each of these Bax mutants were overexpressed in Bax(-/-) MEF or lung cancer H157 cells and the proapoptotic activities were compared. Intriguingly, expression of any of Bax mutants containing the mutation S -> A at S184 (i.e. S184A, EA or AA) represents more potent proapoptotic activity as compared to WT Bax in association with increased 6A7 epitope conformational change, mitochondrial localization/insertion and prolonged half-life. In contrast, all Bax mutants containing the mutation S -> E at S184 (i.e. S184E, AE or EE) have a mobility-shift and fail to insert into mitochondrial membranes with decreased protein stability and less apoptotic activity. Unexpectedly, mutation either S -> A or S -> E at S163 site does not significantly affect the proapoptotic activity of Bax. These findings indicate that S184 but not S163 is the major phosphorylation site for functional regulation of Bax's activity. Therefore, manipulation of the phosphorylation status of Bax at S184 may represent a novel strategy for cancer treatment.
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    Phosphorylation of Human Tristetraprolin in Response to Its Interaction with the CbI Interacting Protein CIN85
    (2010) Kedar, Vishram P; Darby, Martyn K; Williams, Jason G; Blackshear, Perry J
    Background: Tristetraprolin (TTP) is the prototype member of a family of CCCH tandem zinc finger proteins and is considered to be an anti-inflammatory protein in mammals. TTP plays a critical role in the decay of tumor necrosis factor alpha (TNF) mRNA, among others, by binding AU-rich RNA elements in the 3'-untranslated regions of this transcript and promoting its deadenylation and degradation. Methodology/Principal Findings: We used yeast two-hybrid analysis to identify potential protein binding partners for human TTP (hTTP). Various regions of hTTP recovered 31 proteins that fell into 12 categories based on sequence similarities. Among these, the interactions between hTTP and CIN85, cytoplasmic poly (A) binding protein (PABP), nucleolin and heat shock protein 70 were confirmed by co-immunoprecipitation experiments. CIN85 and hTTP co-localized in the cytoplasm of cells as determined by confocal microscopy. CIN85 contains three SH3 domains that specifically bind a unique proline-arginine motif (PXXXPR) found in several CIN85 effectors. We found that the SH3 domains of CIN85 bound to a PXXXPR motif located near the C-terminus of hTTP. Co-expression of CIN85 with hTTP resulted in the increased phosphorylation of hTTP at serine residues in positions 66 and 93, possibly due in part to the demonstrated association of mitogen-activated protein kinase kinase kinase 4 (MEKK4) to both proteins. The presence of CIN85 did not appear to alter hTTP's binding to RNA probes or its stimulated breakdown of TNF mRNA. Conclusions/Significance: These studies describe interactions between hTTP and nucleolin, cytoplasmic PABP, heat shock protein 70 and CIN85; these interactions were initially discovered by two-hybrid analysis, and confirmed by coimmunoprecipitation. We found that CIN85 binding to a C-terminal motif within hTTP led to the increased phosphorylation of hTTP, possibly through enhanced association with MEKK4. The functional consequences to each of the members of this putative complex remain to be determined.
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    Regional Management Units for Marine Turtles: A Novel Framework for Prioritizing Conservation and Research across Multiple Scales
    (2010) Wallace, Bryan P; DiMatteo, Andrew D; Hurley, Brendan J; Finkbeiner, Elena M; Bolten, Alan B; Chaloupka, Milani Y; Hutchinson, Brian J; Abreu-Grobois, F Alberto; Amorocho, Diego; Bjorndal, Karen A; Bourjea, Jerome; Bowen, Brian W; Dueñas, Raquel Briseño; Casale, Paolo; Choudhury, BC; Costa, Alice; Dutton, Peter H; Fallabrino, Alejandro; Girard, Alexandre; Girondot, Marc; Godfrey, Matthew H; Hamann, Mark; López-Mendilaharsu, Milagros; Marcovaldi, Maria Angela; Mortimer, Jeanne A; Musick, John A; Nel, Ronel; Pilcher, Nicolas J; Seminoff, Jeffrey A; Troëng, Sebastian; Witherington, Blair; Mast, Roderic B
    Background: Resolving threats to widely distributed marine megafauna requires definition of the geographic distributions of both the threats as well as the population unit(s) of interest. In turn, because individual threats can operate on varying spatial scales, their impacts can affect different segments of a population of the same species. Therefore, integration of multiple tools and techniques - including site-based monitoring, genetic analyses, mark-recapture studies and telemetry - can facilitate robust definitions of population segments at multiple biological and spatial scales to address different management and research challenges. Methodology/Principal Findings: To address these issues for marine turtles, we collated all available studies on marine turtle biogeography, including nesting sites, population abundances and trends, population genetics, and satellite telemetry. We georeferenced this information to generate separate layers for nesting sites, genetic stocks, and core distributions of population segments of all marine turtle species. We then spatially integrated this information from fine-to coarse-spatial scales to develop nested envelope models, or Regional Management Units (RMUs), for marine turtles globally. Conclusions/Significance: The RMU framework is a solution to the challenge of how to organize marine turtles into units of protection above the level of nesting populations, but below the level of species, within regional entities that might be on independent evolutionary trajectories. Among many potential applications, RMUs provide a framework for identifying data gaps, assessing high diversity areas for multiple species and genetic stocks, and evaluating conservation status of marine turtles. Furthermore, RMUs allow for identification of geographic barriers to gene flow, and can provide valuable guidance to marine spatial planning initiatives that integrate spatial distributions of protected species and human activities. In addition, the RMU framework - including maps and supporting metadata - will be an iterative, user-driven tool made publicly available in an online application for comments, improvements, download and analysis.
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    Representation of Global and National Conservation Priorities by Colombia's Protected Area Network
    (2010) Forero-Medina, German; Joppa, Lucas
    Background: How do national-level actions overlap with global priorities for conservation? Answering this question is especially important in countries with high and unique biological diversity like Colombia. Global biodiversity schemes provide conservation guidance at a large scale, while national governments gazette land for protection based on a combination of criteria at regional or local scales. Information on how a protected area network represents global and national conservation priorities is crucial for finding gaps in coverage and for future expansion of the system. Methodology/Principal Findings: We evaluated the agreement of Colombia's protected area network with global conservation priorities, and the extent to which the network reflects the country's biomes, species richness, and common environmental and physical conditions. We used this information to identify priority biomes for conservation. We find the dominant strategy in Colombia has been a proactive one, allocating the highest proportion of protected land on intact, difficult to access and species rich areas like the Amazon. Threatened and unique areas are disproportionately absent from Colombia's protected lands. We highlight six biomes in Colombia as conservation priorities that should be considered in any future expansion of Colombia's protected area network. Two of these biomes have less than 3% of their area protected and more than 70% of their area transformed for human use. One has less than 3% protected and high numbers of threatened vertebrates. Three biomes fall in both categories. Conclusions: Expansion of Colombia's Protected Area Network should consider the current representativeness of the network. We indicate six priority biomes that can contribute to improving the representation of threatened species and biomes in Colombia.
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    Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Models
    (2008) Raymond, Scott B; Treat, Lisa H; Dewey, Jonathan D; McDannold, Nathan J; Hynynen, Kullervo; Bacskai, Brian J
    Alzheimer's disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimer's disease with amyloid pathology. MRI guidance permitted selective treatment and monitoring of plaque-heavy anatomical regions, such as the hippocampus. Treated brain regions exhibited 16.5 +/- 5.4-fold increase in Trypan blue fluorescence and 2.7 +/- 1.2-fold increase in anti-amyloid antibodies that localized to amyloid plaques. Ultrasound-enhanced delivery was consistently reproduced in two different transgenic strains (APPswe:PSEN1dE9, PDAPP), across a large age range (9-26 months), with and without MR guidance, and with little or no tissue damage. Ultrasound-mediated, transient blood-brain barrier disruption allows the delivery of both therapeutic and molecular imaging agents in Alzheimer's mouse models, which should aid pre-clinical drug screening and imaging probe development. Furthermore, this technique may be used to deliver a wide variety of small and large molecules to the brain for imaging and therapy in other neurodegenerative diseases.