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Sample records for identify binding hotspots

  1. Identifying Interactions that Determine Fragment Binding at Protein Hotspots.

    Science.gov (United States)

    Radoux, Chris J; Olsson, Tjelvar S G; Pitt, Will R; Groom, Colin R; Blundell, Tom L

    2016-05-12

    Locating a ligand-binding site is an important first step in structure-guided drug discovery, but current methods do little to suggest which interactions within a pocket are the most important for binding. Here we illustrate a method that samples atomic hotspots with simple molecular probes to produce fragment hotspot maps. These maps specifically highlight fragment-binding sites and their corresponding pharmacophores. For ligand-bound structures, they provide an intuitive visual guide within the binding site, directing medicinal chemists where to grow the molecule and alerting them to suboptimal interactions within the original hit. The fragment hotspot map calculation is validated using experimental binding positions of 21 fragments and subsequent lead molecules. The ligands are found in high scoring areas of the fragment hotspot maps, with fragment atoms having a median percentage rank of 97%. Protein kinase B and pantothenate synthetase are examined in detail. In each case, the fragment hotspot maps are able to rationalize a Free-Wilson analysis of SAR data from a fragment-based drug design project.

  2. Peptides identify multiple hotspots within the ligand binding domain of the TNF receptor 2

    Directory of Open Access Journals (Sweden)

    Lennick Michael

    2003-01-01

    Full Text Available Abstract Background Hotspots are defined as the minimal functional domains involved in protein:protein interactions and sufficient to induce a biological response. Results Here we describe the use of complex and high diversity phage display libraries to isolate peptides (called Hotspot Ligands or HSPLs which sub-divide the ligand binding domain of the tumor necrosis factor receptor 2 (TNFR2; p75 into multiple hotspots. We have shown that these libraries could generate HSPLs which not only subdivide hotspots on protein and non-protein targets but act as agonists or antagonists. Using this approach, we generated peptides which were specific for human TNFR2, could be competed by the natural ligands, TNFα and TNFβ and induced an unexpected biological response in a TNFR2-specific manner. Conclusions To our knowledge, this is the first report describing the dissection of the TNFR2 into biologically active hotspots with the concomitant identification of a novel and unexpected biological activity.

  3. Epigenetic functions enriched in transcription factors binding to mouse recombination hotspots.

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    Wu, Min; Kwoh, Chee-Keong; Przytycka, Teresa M; Li, Jing; Zheng, Jie

    2012-06-21

    The regulatory mechanism of recombination is a fundamental problem in genomics, with wide applications in genome-wide association studies, birth-defect diseases, molecular evolution, cancer research, etc. In mammalian genomes, recombination events cluster into short genomic regions called "recombination hotspots". Recently, a 13-mer motif enriched in hotspots is identified as a candidate cis-regulatory element of human recombination hotspots; moreover, a zinc finger protein, PRDM9, binds to this motif and is associated with variation of recombination phenotype in human and mouse genomes, thus is a trans-acting regulator of recombination hotspots. However, this pair of cis and trans-regulators covers only a fraction of hotspots, thus other regulators of recombination hotspots remain to be discovered. In this paper, we propose an approach to predicting additional trans-regulators from DNA-binding proteins by comparing their enrichment of binding sites in hotspots. Applying this approach on newly mapped mouse hotspots genome-wide, we confirmed that PRDM9 is a major trans-regulator of hotspots. In addition, a list of top candidate trans-regulators of mouse hotspots is reported. Using GO analysis we observed that the top genes are enriched with function of histone modification, highlighting the epigenetic regulatory mechanisms of recombination hotspots.

  4. Identifying the Species Threat Hotspots from Global Supply Chains

    OpenAIRE

    Moran, Daniel; Kanemoto, Keiichiro

    2016-01-01

    Identifying species threat hotspots has been a successful approach for setting conservation priorities. One major challenge in conservation is that in many hotspots export industries continue to drive overexploitation. Conservation measures must consider not just the point of impact, but also the consumer demand that ultimately drives resource use. To understand which species threat hotspots are driven by which consumers, we have developed a new approach to link a set of biodiversity footprin...

  5. Identifying species threat hotspots from global supply chains.

    Science.gov (United States)

    Moran, Daniel; Kanemoto, Keiichiro

    2017-01-04

    Identifying hotspots of species threat has been a successful approach for setting conservation priorities. One important challenge in conservation is that, in many hotspots, export industries continue to drive overexploitation. Conservation measures must consider not just the point of impact, but also the consumer demand that ultimately drives resource use. To understand which species threat hotspots are driven by which consumers, we have developed a new approach to link a set of biodiversity footprint accounts to the hotspots of threatened species on the IUCN Red List of Threatened Species. The result is a map connecting consumption to spatially explicit hotspots driven by production on a global scale. Locating biodiversity threat hotspots driven by consumption of goods and services can help to connect conservationists, consumers, companies and governments in order to better target conservation actions.

  6. Identifying hotspots and management of critical ecosystem services in rapidly urbanizing Yangtze River Delta Region, China.

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    Cai, Wenbo; Gibbs, David; Zhang, Lang; Ferrier, Graham; Cai, Yongli

    2017-04-15

    Rapid urbanization has altered many ecosystems, causing a decline in many ecosystem services, generating serious ecological crisis. To cope with these challenges, we presented a comprehensive framework comprising five core steps for identifying and managing hotspots of critical ecosystem services in a rapid urbanizing region. This framework was applied in the case study of the Yangtze River Delta (YRD) Region. The study showed that there was large spatial heterogeneity in the hotspots of ecosystem services in the region, hotspots of supporting services and regulating services aggregately distributing in the southwest mountainous areas while hotspots of provisioning services mainly in the northeast plain, and hotspots of cultural services widespread in the waterbodies and southwest mountainous areas. The regionalization of the critical ecosystem services was made through the hotspot analysis. This study provided valuable information for environmental planning and management in a rapid urbanizing region and helped improve China's ecological redlines policy at regional scale. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Effectively identifying regulatory hotspots while capturing expression heterogeneity in gene expression studies

    Science.gov (United States)

    2014-01-01

    Expression quantitative trait loci (eQTL) mapping is a tool that can systematically identify genetic variation affecting gene expression. eQTL mapping studies have shown that certain genomic locations, referred to as regulatory hotspots, may affect the expression levels of many genes. Recently, studies have shown that various confounding factors may induce spurious regulatory hotspots. Here, we introduce a novel statistical method that effectively eliminates spurious hotspots while retaining genuine hotspots. Applied to simulated and real datasets, we validate that our method achieves greater sensitivity while retaining low false discovery rates compared to previous methods. PMID:24708878

  8. Identifying biodiversity hotspots for threatened mammal species in Iran

    NARCIS (Netherlands)

    Farashi, Azita; Shariati Najafabadi, Mitra; Hosseini, Mahshid

    2017-01-01

    Conservation biology has much more attention for biodiversity hot spots than before. In order to recognize the hotspots for Iranian terrestrial mammal species that are listed in any red list, nationally or globally, ten Species Distribution Models (SDMs) have been applied. The SDMs evaluation

  9. Predicted MHC peptide binding promiscuity explains MHC class I 'hotspots' of antigen presentation defined by mass spectrometry eluted ligand data.

    Science.gov (United States)

    Jappe, Emma Christine; Kringelum, Jens; Trolle, Thomas; Nielsen, Morten

    2018-02-15

    Peptides that bind to and are presented by MHC class I and class II molecules collectively make up the immunopeptidome. In the context of vaccine development, an understanding of the immunopeptidome is essential, and much effort has been dedicated to its accurate and cost-effective identification. Current state-of-the-art methods mainly comprise in silico tools for predicting MHC binding, which is strongly correlated with peptide immunogenicity. However, only a small proportion of the peptides that bind to MHC molecules are, in fact, immunogenic, and substantial work has been dedicated to uncovering additional determinants of peptide immunogenicity. In this context, and in light of recent advancements in mass spectrometry (MS), the existence of immunological hotspots has been given new life, inciting the hypothesis that hotspots are associated with MHC class I peptide immunogenicity. We here introduce a precise terminology for defining these hotspots and carry out a systematic analysis of MS and in silico predicted hotspots. We find that hotspots defined from MS data are largely captured by peptide binding predictions, enabling their replication in silico. This leads us to conclude that hotspots, to a great degree, are simply a result of promiscuous HLA binding, which disproves the hypothesis that the identification of hotspots provides novel information in the context of immunogenic peptide prediction. Furthermore, our analyses demonstrate that the signal of ligand processing, although present in the MS data, has very low predictive power to discriminate between MS and in silico defined hotspots. © 2018 John Wiley & Sons Ltd.

  10. Identifying Genetic Hotspots by Mapping Molecular Diversity of Widespread Trees: When Commonness Matters.

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    Souto, Cintia P; Mathiasen, Paula; Acosta, María Cristina; Quiroga, María Paula; Vidal-Russell, Romina; Echeverría, Cristian; Premoli, Andrea C

    2015-01-01

    Conservation planning requires setting priorities at the same spatial scale at which decision-making processes are undertaken considering all levels of biodiversity, but current methods for identifying biodiversity hotspots ignore its genetic component. We developed a fine-scale approach based on the definition of genetic hotspots, which have high genetic diversity and unique variants that represent their evolutionary potential and evolutionary novelties. Our hypothesis is that wide-ranging taxa with similar ecological tolerances, yet of phylogenetically independent lineages, have been and currently are shaped by ecological and evolutionary forces that result in geographically concordant genetic patterns. We mapped previously published genetic diversity and unique variants of biparentally inherited markers and chloroplast sequences for 9 species from 188 and 275 populations, respectively, of the 4 woody dominant families of the austral temperate forest, an area considered a biodiversity hotspot. Spatial distribution patterns of genetic polymorphisms differed among taxa according to their ecological tolerances. Eight genetic hotspots were detected and we recommend conservation actions for some in the southern Coastal Range in Chile. Existing spatially explicit genetic data from multiple populations and species can help to identify biodiversity hotspots and guide conservation actions to establish science-based protected areas that will preserve the evolutionary potential of key habitats and species. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. A framework for identifying carbon hotspots and forest management drivers

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    Nilesh Timilsina; Francisco J. Escobedo; Wendell P. Cropper; Amr Abd-Elrahman; Thomas Brandeis; Sonia Delphin; Samuel Lambert

    2013-01-01

    Spatial analyses of ecosystem system services that are directly relevant to both forest management decision making and conservation in the subtropics are rare. Also, frameworks that identify and map carbon stocks and corresponding forest management drivers using available regional, national, and international-level forest inventory datasets could provide insights into...

  12. Identifying ecosystem service hotspots for environmental management in Durban, South Africa

    Directory of Open Access Journals (Sweden)

    Rashieda Davids

    2016-12-01

    Conclusion: The results indicated that substantial portions of hotspot areas lie outside of formally regulated and managed conservation areas and remain vulnerable to human impact and habitat degradation. The study identified management areas and options that could yield maximum benefits; including the need for the development of an ecosystem services management and protection strategy, the selection of areas for co-management of ecosystem service hotspots and CBAs and the need for collaborative management.

  13. Identifying fish diversity hot-spots in data-poor situations.

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    Fonseca, Vinícius Prado; Pennino, Maria Grazia; de Nóbrega, Marcelo Francisco; Oliveira, Jorge Eduardo Lins; de Figueiredo Mendes, Liana

    2017-08-01

    One of the more challenging tasks in Marine Spatial Planning (MSP) is identifying critical areas for management and conservation of fish stocks. However, this objective is difficult to achieve in data-poor situations with different sources of uncertainty. In the present study we propose a combination of hierarchical Bayesian spatial models and remotely sensed estimates of environmental variables to be used as flexible and reliable statistical tools to identify and map fish species richness and abundance hot-spots. Results show higher species aggregates in areas with higher sea floor rugosity and habitat complexity, and identify clear richness hot-spots. Our findings identify sensitive habitats through essential and easy-to-use interpretation tools, such as predictive maps, which can contribute to improving management and operability of the studied data-poor situations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. General Practice Clinical Data Help Identify Dementia Hotspots: A Novel Geospatial Analysis Approach.

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    Bagheri, Nasser; Wangdi, Kinley; Cherbuin, Nicolas; Anstey, Kaarin J

    2018-01-01

    We have a poor understanding of whether dementia clusters geographically, how this occurs, and how dementia may relate to socio-demographic factors. To shed light on these important questions, this study aimed to compute a dementia risk score for individuals to assess spatial variation of dementia risk, identify significant clusters (hotspots), and explore their association with socioeconomic status. We used clinical records from 16 general practices (468 Statistical Area level 1 s, N = 14,746) from the city of west Adelaide, Australia for the duration of 1 January 2012 to 31 December 2014. Dementia risk was estimated using The Australian National University-Alzheimer's Disease Risk Index. Hotspot analyses were applied to examine potential clusters in dementia risk at small area level. Significant hotspots were observed in eastern and southern areas while coldspots were observed in the western area within the study perimeter. Additionally, significant hotspots were observed in low socio-economic communities. We found dementia risk scores increased with age, sex (female), high cholesterol, no physical activity, living alone (widow, divorced, separated, or never married), and co-morbidities such as diabetes and depression. Similarly, smoking was associated with a lower dementia risk score. The identification of dementia risk clusters may provide insight into possible geographical variations in risk factors for dementia and quantify these risks at the community level. As such, this research may enable policy makers to tailor early prevention strategies to the correct individuals within their precise locations.

  15. Identifying Victims of Human Trafficking at Hotspots by Focusing on People Smuggled to Europe

    Directory of Open Access Journals (Sweden)

    Matilde Ventrella

    2017-06-01

    Full Text Available Research has shown that smuggling of migrants is associated with human trafficking. Hence, victims of human trafficking amongst smuggled migrants should be identified by EU Member States at hotspots established by the European Commission, to overcome the migrant and refugee crisis. Identified victims should be given a visa and a programme of protection to escape their traffickers. In order to achieve these objectives, research suggests that EU law on migrant smuggling should be amended and the Temporary Protection Directive should be applied to smuggled persons when there is an indication that they may be victims of human trafficking. This approach should be adopted by the EASO in cooperation with police forces investigating smuggling and trafficking at hotspots.

  16. Identifying cholera "hotspots" in Uganda: An analysis of cholera surveillance data from 2011 to 2016

    OpenAIRE

    Bwire, Godfrey; Ali, Mohammad; Sack, David A.; Nakinsige, Anne; Naigaga, Martha; Debes, Amanda K.; Ngwa, Moise C.; Brooks, W. Abdullah; Garimoi Orach, Christopher

    2017-01-01

    Background Despite advance in science and technology for prevention, detection and treatment of cholera, this infectious disease remains a major public health problem in many countries in sub-Saharan Africa, Uganda inclusive. The aim of this study was to identify cholera hotspots in Uganda to guide the development of a roadmap for prevention, control and elimination of cholera in the country. Methodology/Principle findings We obtained district level confirmed cholera outbreak data from 2011 t...

  17. A multi-indicator approach for identifying shoreline sewage pollution hotspots adjacent to coral reefs.

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    Abaya, Leilani M; Wiegner, Tracy N; Colbert, Steven L; Beets, James P; Carlson, Kaile'a M; Kramer, K Lindsey; Most, Rebecca; Couch, Courtney S

    2018-04-01

    Sewage pollution is contributing to the global decline of coral reefs. Identifying locations where it is entering waters near reefs is therefore a management priority. Our study documented shoreline sewage pollution hotspots in a coastal community with a fringing coral reef (Puakō, Hawai'i) using dye tracer studies, sewage indicator measurements, and a pollution scoring tool. Sewage reached shoreline waters within 9 h to 3 d. Fecal indicator bacteria concentrations were high and variable, and δ 15 N macroalgal values were indicative of sewage at many stations. Shoreline nutrient concentrations were two times higher than those in upland groundwater. Pollution hotspots were identified with a scoring tool using three sewage indicators. It confirmed known locations of sewage pollution from dye tracer studies. Our study highlights the need for a multi-indicator approach and scoring tool to identify sewage pollution hotspots. This approach will be useful for other coastal communities grappling with sewage pollution. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Identifying multidrug resistant tuberculosis transmission hotspots using routinely collected data12

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    Manjourides, Justin; Lin, Hsien-Ho; Shin, Sonya; Jeffery, Caroline; Contreras, Carmen; Cruz, Janeth Santa; Jave, Oswaldo; Yagui, Martin; Asencios, Luis; Pagano, Marcello; Cohen, Ted

    2012-01-01

    SUMMARY In most countries with large drug resistant tuberculosis epidemics, only those cases that are at highest risk of having MDRTB receive a drug sensitivity test (DST) at the time of diagnosis. Because of this prioritized testing, identification of MDRTB transmission hotspots in communities where TB cases do not receive DST is challenging, as any observed aggregation of MDRTB may reflect systematic differences in how testing is distributed in communities. We introduce a new disease mapping method, which estimates this missing information through probability–weighted locations, to identify geographic areas of increased risk of MDRTB transmission. We apply this method to routinely collected data from two districts in Lima, Peru over three consecutive years. This method identifies an area in the eastern part of Lima where previously untreated cases have increased risk of MDRTB. This may indicate an area of increased transmission of drug resistant disease, a finding that may otherwise have been missed by routine analysis of programmatic data. The risk of MDR among retreatment cases is also highest in these probable transmission hotspots, though a high level of MDR among retreatment cases is present throughout the study area. Identifying potential multidrug resistant tuberculosis (MDRTB) transmission hotspots may allow for targeted investigation and deployment of resources. PMID:22401962

  19. Identifying cholera "hotspots" in Uganda: An analysis of cholera surveillance data from 2011 to 2016.

    Science.gov (United States)

    Bwire, Godfrey; Ali, Mohammad; Sack, David A; Nakinsige, Anne; Naigaga, Martha; Debes, Amanda K; Ngwa, Moise C; Brooks, W Abdullah; Garimoi Orach, Christopher

    2017-12-01

    Despite advance in science and technology for prevention, detection and treatment of cholera, this infectious disease remains a major public health problem in many countries in sub-Saharan Africa, Uganda inclusive. The aim of this study was to identify cholera hotspots in Uganda to guide the development of a roadmap for prevention, control and elimination of cholera in the country. We obtained district level confirmed cholera outbreak data from 2011 to 2016 from the Ministry of Health, Uganda. Population and rainfall data were obtained from the Uganda Bureau of Statistics, and water, sanitation and hygiene data from the Ministry of Water and Environment. A spatial scan test was performed to identify the significantly high risk clusters. Cholera hotspots were defined as districts whose center fell within a significantly high risk cluster or where a significantly high risk cluster was completely superimposed onto a district. A zero-inflated negative binomial regression model was employed to identify the district level risk factors for cholera. In total 11,030 cases of cholera were reported during the 6-year period. 37(33%) of 112 districts reported cholera outbreaks in one of the six years, and 20 (18%) districts experienced cholera at least twice in those years. We identified 22 districts as high risk for cholera, of which 13 were near a border of Democratic Republic of Congo (DRC), while 9 districts were near a border of Kenya. The relative risk of having cholera inside the high-risk districts (hotspots) were 2 to 22 times higher than elsewhere in the country. In total, 7 million people were within cholera hotspots. The negative binomial component of the ZINB model shows people living near a lake or the Nile river were at increased risk for cholera (incidence rate ratio, IRR = 0.98, 95% CI: 0.97 to 0.99, p cholera in a district (IRR = 0.99, 95% CI: 0.98 to 1.00, p = .02 and IRR = 1.02, 95% CI: 1.01 to 1.03, p cholera in the district. The study identified cholera

  20. Identifying malaria hotspots in Keur Soce health and demographic surveillance site in context of low transmission.

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    Ndiath, Mansour; Faye, Babacar; Cisse, Badara; Ndiaye, Jean Louis; Gomis, Jules François; Dia, Anta Tal; Gaye, Oumar

    2014-11-24

    Malaria is major public health problem in Senegal. In some parts of the country, it occurs almost permanently with a seasonal increase during the rainy season. There is evidence to suggest that the prevalence of malaria in Senegal has decreased considerably during the past few years. Recent data from the Senegalese National Malaria Control Programme (NMCP) indicates that the number of malaria cases decrease from 1,500,000 in 2006 to 174,339 in 2010. With the decline of malaria morbidity in Senegal, the characterization of the new epidemiological profile of this disease is crucial for public health decision makers. SaTScan™ software using the Kulldorf method of retrospective space-time permutation and the Bernoulli purely spatial model was used to identify malaria clusters using confirmed malaria cases in 74 villages. ArcMAp was used to map malaria hotspots. Logistic regression was used to investigate risk factors for malaria hotspots in Keur Soce health and demographic surveillance site. A total of 1,614 individuals in 440 randomly selected households were enrolled. The overall malaria prevalence was 12%. The malaria prevalence during the study period varied from less than 2% to more than 25% from one village to another. The results showed also that rooms located between 50 m to 100 m away from livestock holding place [adjusted O.R = 0.7, P = 0.044, 95% C.I (1.02 - 7.42)], bed net use [adjusted O.R = 1.2, P = 0.024, 95% C.I (1.02 -1.48)], are good predictors for malaria hotspots in the Keur Soce health and demographic surveillance site. The socio economic status of the household also predicted on hotspots patterns. The less poor household are 30% less likely to be classified as malaria hotspots area compared to the poorest household [adjusted O.R = 0.7, P = 0.014, 95% C.I (0.47 - 0.91)]. The study investigated risk factors for malaria hotspots in small communities in the Keur Soce site. The result showed considerable variation of malaria

  1. Highly accessible AU-rich regions in 3’ untranslated regions are hotspots for binding of regulatory factors

    Science.gov (United States)

    2017-01-01

    Post-transcriptional regulation is regarded as one of the major processes involved in the regulation of gene expression. It is mainly performed by RNA binding proteins and microRNAs, which target RNAs and typically affect their stability. Recent efforts from the scientific community have aimed at understanding post-transcriptional regulation at a global scale by using high-throughput sequencing techniques such as cross-linking and immunoprecipitation (CLIP), which facilitates identification of binding sites of these regulatory factors. However, the diversity in the experimental procedures and bioinformatics analyses has hindered the integration of multiple datasets and thus limited the development of an integrated view of post-transcriptional regulation. In this work, we have performed a comprehensive analysis of 107 CLIP datasets from 49 different RBPs in HEK293 cells to shed light on the complex interactions that govern post-transcriptional regulation. By developing a more stringent CLIP analysis pipeline we have discovered the existence of conserved regulatory AU-rich regions in the 3’UTRs where miRNAs and RBPs that regulate several processes such as polyadenylation or mRNA stability bind. Analogous to promoters, many factors have binding sites overlapping or in close proximity in these hotspots and hence the regulation of the mRNA may depend on their relative concentrations. This hypothesis is supported by RBP knockdown experiments that alter the relative concentration of RBPs in the cell. Upon AGO2 knockdown (KD), transcripts containing “free” target sites show increased expression levels compared to those containing target sites in hotspots, which suggests that target sites within hotspots are less available for miRNAs to bind. Interestingly, these hotspots appear enriched in genes with regulatory functions such as DNA binding and RNA binding. Taken together, our results suggest that hotspots are functional regulatory elements that define an extra layer

  2. Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity

    Science.gov (United States)

    Cole, David K.; Bulek, Anna M.; Dolton, Garry; Schauenberg, Andrea J.; Szomolay, Barbara; Trimby, Andrew; Jothikumar, Prithiviraj; Fuller, Anna; Skowera, Ania; Rossjohn, Jamie; Zhu, Cheng; Miles, John J.; Wooldridge, Linda; Rizkallah, Pierre J.; Sewell, Andrew K.

    2016-01-01

    The cross-reactivity of T cells with pathogen- and self-derived peptides has been implicated as a pathway involved in the development of autoimmunity. However, the mechanisms that allow the clonal T cell antigen receptor (TCR) to functionally engage multiple peptide–major histocompatibility complexes (pMHC) are unclear. Here, we studied multiligand discrimination by a human, preproinsulin reactive, MHC class-I–restricted CD8+ T cell clone (1E6) that can recognize over 1 million different peptides. We generated high-resolution structures of the 1E6 TCR bound to 7 altered peptide ligands, including a pathogen-derived peptide that was an order of magnitude more potent than the natural self-peptide. Evaluation of these structures demonstrated that binding was stabilized through a conserved lock-and-key–like minimal binding footprint that enables 1E6 TCR to tolerate vast numbers of substitutions outside of this so-called hotspot. Highly potent antigens of the 1E6 TCR engaged with a strong antipathogen-like binding affinity; this engagement was governed though an energetic switch from an enthalpically to entropically driven interaction compared with the natural autoimmune ligand. Together, these data highlight how T cell cross-reactivity with pathogen-derived antigens might break self-tolerance to induce autoimmune disease. PMID:27183389

  3. Using a distribution and conservation status weighted hotspot approach to identify areas in need of conservation action to benefit Idaho bird species

    Science.gov (United States)

    Haines, Aaron M.; Leu, Matthias; Svancara, Leona K.; Wilson, Gina; Scott, J. Michael

    2010-01-01

    Identification of biodiversity hotspots (hereafter, hotspots) has become a common strategy to delineate important areas for wildlife conservation. However, the use of hotspots has not often incorporated important habitat types, ecosystem services, anthropogenic activity, or consistency in identifying important conservation areas. The purpose of this study was to identify hotspots to improve avian conservation efforts for Species of Greatest Conservation Need (SGCN) in the state of Idaho, United States. We evaluated multiple approaches to define hotspots and used a unique approach based on weighting species by their distribution size and conservation status to identify hotspot areas. All hotspot approaches identified bodies of water (Bear Lake, Grays Lake, and American Falls Reservoir) as important hotspots for Idaho avian SGCN, but we found that the weighted approach produced more congruent hotspot areas when compared to other hotspot approaches. To incorporate anthropogenic activity into hotspot analysis, we grouped species based on their sensitivity to specific human threats (i.e., urban development, agriculture, fire suppression, grazing, roads, and logging) and identified ecological sections within Idaho that may require specific conservation actions to address these human threats using the weighted approach. The Snake River Basalts and Overthrust Mountains ecological sections were important areas for potential implementation of conservation actions to conserve biodiversity. Our approach to identifying hotspots may be useful as part of a larger conservation strategy to aid land managers or local governments in applying conservation actions on the ground.

  4. A hotspot in the glucocorticoid receptor DNA-binding domain susceptible to loss of function mutation

    Science.gov (United States)

    Banuelos, Jesus; Shin, Soon Cheon; Lu, Nick Z.

    2015-01-01

    Glucocorticoids (GCs) are used to treat a variety of inflammatory disorders and certain cancers. However, GC resistance occurs in subsets of patients. We found that EL4 cells, a GC-resistant mouse thymoma cell line, harbored a point mutation in their GC receptor (GR) gene, resulting in the substitution of arginine 493 by a cysteine in the second zinc finger of the DNA-binding domain. Allelic discrimination analyses revealed that the R493C mutation occurred on both alleles. In the absence of GCs, the GR in EL4 cells localized predominantly in the cytoplasm and upon dexamethasone treatment underwent nuclear translocation, suggesting the ligand binding ability of the GR in EL4 cells was intact. In transient transfection assays, the R493C mutant could not transactivate the MMTV-luciferase reporter. Site-directed mutagenesis to revert the R493C mutation restored the transactivation activity. Cotransfection experiments showed that the R493C mutant did not inhibit the transcriptional activities of the wild-type GR. In addition, the R493C mutant did not repress either the AP-1 or NF-κB reporters as effectively as WT GR. Furthermore, stable expression of the WT GR in the EL4 cells enabled GC-mediated gene regulation, specifically upregulation of IκBα and downregulation of interferon γ and interleukin 17A. Arginine 493 is conserved among multiple species and all human nuclear receptors and its mutation has also been found in the human GR, androgen receptor, and mineralocorticoid receptor. Thus, R493 is necessary for the transcriptional activity of the GR and a hotspot for mutations that result in GC resistance. PMID:25676786

  5. Identifying Local Hotspots of Pediatric Chronic Diseases Using Emergency Department Surveillance

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    Lee, David C.; Yi, Stella S.; Fong, Hiu-Fai; Athens, Jessica K.; Ravenell, Joseph E.; Sevick, Mary Ann; Wall, Stephen P.; Elbel, Brian

    2016-01-01

    Objective To use novel geographic methods and large-scale claims data to identify the local distribution of pediatric chronic diseases in New York City. Methods Using a 2009 all-payer emergency claims database, we identified the proportion of unique children aged 0 to 17 with diagnosis codes for specific medical and psychiatric conditions. As a proof of concept, we compared these prevalence estimates to traditional health surveys and registry data using the most geographically granular data available. In addition, we used home addresses to map local variation in pediatric disease burden. Results We identified 549,547 New York City children who visited an emergency department at least once in 2009. Though our sample included more publicly insured and uninsured children, we found moderate to strong correlations of prevalence estimates when compared to health surveys and registry data at pre-specified geographic levels. Strongest correlations were found for asthma and mental health conditions by county among younger children (0.88, p=0.05 and 0.99, pdisease prevalence with higher geographic resolution. More studies are needed to investigate limitations of these methods and assess reliability of local disease estimates. What’s New This study demonstrated how emergency department surveillance may improve estimates of pediatric disease prevalence with higher geographic resolution. We identified 29% of New York City children with a single year of data and identified local hotspots of pediatric chronic diseases. PMID:28385326

  6. Identifying Social Impacts in Product Supply Chains:Overview and Application of the Social Hotspot Database

    Directory of Open Access Journals (Sweden)

    Gregory Norris

    2012-08-01

    Full Text Available One emerging tool to measure the social-related impacts in supply chains is Social Life Cycle Assessment (S-LCA, a derivative of the well-established environmental LCA technique. LCA has recently started to gain popularity among large corporations and initiatives, such as The Sustainability Consortium or the Sustainable Apparel Coalition. Both have made the technique a cornerstone of their applied-research program. The Social Hotspots Database (SHDB is an overarching, global database that eases the data collection burden in S-LCA studies. Proposed “hotspots” are production activities or unit processes (also defined as country-specific sectors in the supply chain that may be at risk for social issues to be present. The SHDB enables efficient application of S-LCA by allowing users to prioritize production activities for which site-specific data collection is most desirable. Data for three criteria are used to inform prioritization: (1 labor intensity in worker hours per unit process and (2 risk for, or opportunity to affect, relevant social themes or sub-categories related to Human Rights, Labor Rights and Decent Work, Governance and Access to Community Services (3 gravity of a social issue. The Worker Hours Model was developed using a global input/output economic model and wage rate data. Nearly 200 reputable sources of statistical data have been used to develop 20 Social Theme Tables by country and sector. This paper presents an overview of the SHDB development and features, as well as results from a pilot study conducted on strawberry yogurt. This study, one of seven Social Scoping Assessments mandated by The Sustainability Consortium, identifies the potential social hotspots existing in the supply chain of strawberry yogurt. With this knowledge, companies that manufacture or sell yogurt can refine their data collection efforts in order to put their social responsibility performance in perspective and effectively set up programs and

  7. Identifying pollination service hotspots and coldspots using citizen science data from the Great Sunflower Project

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    LeBuhn, G.; Schmucki, R.

    2016-12-01

    Identifying the spatial patterns of pollinator visitation rates is key to identifying the drivers of differences in pollination service and the areas where pollinator conservation will provide the highest return on investment. However, gathering pollinator abundance data at the appropriate regional and national scales is untenable. As a surrogate, habitat models have been developed to identify areas of pollinator losses but these models have been developed using expert opinion based on foraging and nesting requirements. Thousands of citizen scientists across the United States participating in The Great Sunflower Project (www.GreatSunflower.org) contribute timed counts of pollinator visits to a focal sunflower variety planted in local gardens and green spaces. While these data provide a more direct measure of pollination service to a standardized plant and include a measure of effort, the data are complicated. Each location is sampled at different dates, times and frequencies as well as different points across the local flight season. To overcome this complication, we have used a generalized additive model to generate regional flight curves to calibrate each individual data point and to attain better estimates of pollination service at each site. Using these flight season corrected data, we identify hotspots and cold spots in pollinator service across the United States, evaluate the drivers shaping the spatial patterns and observe how these data align with the results obtained from predictive models that are based on expert knowledge on foraging and nesting habitats.

  8. Identifying Pelagic Habitat Hotspots of Neon Flying Squid in the Temperate Waters of the Central North Pacific.

    Science.gov (United States)

    Alabia, Irene D; Saitoh, Sei-Ichi; Mugo, Robinson; Igarashi, Hiromichi; Ishikawa, Yoichi; Usui, Norihisa; Kamachi, Masafumi; Awaji, Toshiyuki; Seito, Masaki

    2015-01-01

    We identified the pelagic habitat hotspots of the neon flying squid (Ommastrephes bartramii) in the central North Pacific from May to July and characterized the spatial patterns of squid aggregations in relation to oceanographic features such as mesoscale oceanic eddies and the Transition Zone Chlorophyll-a Front (TZCF). The data used for the habitat model construction and analyses were squid fishery information, remotely-sensed and numerical model-derived environmental data from May to July 1999-2010. Squid habitat hotspots were deduced from the monthly Maximum Entropy (MaxEnt) models and were identified as regions of persistent high suitable habitat across the 12-year period. The distribution of predicted squid habitat hotspots in central North Pacific revealed interesting spatial and temporal patterns likely linked with the presence and dynamics of oceanographic features in squid's putative foraging grounds from late spring to summer. From May to June, the inferred patches of squid habitat hotspots developed within the Kuroshio-Oyashio transition zone (KOTZ; 37-40°N) and further expanded north towards the subarctic frontal zone (SAFZ; 40-44°N) in July. The squid habitat hotspots within the KOTZ and areas west of the dateline (160°W-180°) were likely influenced and associated with the highly dynamic and transient oceanic eddies and could possibly account for lower squid suitable habitat persistence obtained from these regions. However, predicted squid habitat hotspots located in regions east of the dateline (180°-160°W) from June to July, showed predominantly higher squid habitat persistence presumably due to their proximity to the mean position of the seasonally-shifting TZCF and consequent utilization of the highly productive waters of the SAFZ.

  9. Identifying hotspots of coastal risk and evaluating DRR measures: results from the RISC-KIT project.

    Science.gov (United States)

    Van Dongeren, A.; Ciavola, P.; Viavattene, C.; Dekleermaeker, S.; Martinez, G.; Ferreira, O.; Costa, C.

    2016-02-01

    High-impact storm events have demonstrated the vulnerability of coastal zones in Europe and beyond. These impacts are likely to increase due to predicted climate change and ongoing coastal development. In order to reduce impacts, disaster risk reduction (DRR) measures need to be taken, which prevent or mitigate the effects of storm events. To drive the DRR agenda, the UNISDR formulated the Sendai Framework for Action, and the EU has issued the Floods Directive. However, neither is specific about the methods to be used to develop actionable DRR measures in the coastal zone. Therefore, there is a need to develop methods, tools and approaches which make it possible to: identify and prioritize the coastal zones which are most at risk through a Coastal Risk Assessment Framework, evaluate the effectiveness of DRR options for these coastal areas, using an Early Warning/Decision Support System, which can be used both in the planning and event-phase. This paper gives an overview of the products and results obtained in the FP7-funded project RISC-KIT, which aims to develop and apply a set of tools with which highly-vulnerable coastal areas (so-called "hotspots") can be identified. The identification is done using the Coastal Risk Assessment Framework, or CRAF, which computes the intensity from multi-hazards, the exposure and the vulnerability, all components of risk, including network and cascading effects. Based on this analysis hot spots of risk which warrant coastal protection investments are selected. For these hotspot areas, high-resolution Early Warning and Decision Support Tools are developed with which it is possible to compute in detail the effectiveness of Disaster Risk Reduction measures in storm event scenarios, which helps decide which measures to implement in the planning phase. The same systems, but now driven with real time data, can also be used for early warning systems. All tools are tested on eleven case study areas, at least one on each EU Regional Sea

  10. Identifying Water Insecurity Hotspots in the Lake Victoria Basin of Eastern Africa

    Science.gov (United States)

    Pricope, N. G.; Shukla, S.; Linard, C.; Gaughan, A.

    2014-12-01

    The Lake Victoria Basin (LVB), one of Africa's most populated transboundary watersheds and home to more than 30 million inhabitants, is increasingly challenged by both water quality problems and water quantity shortages against a backdrop of climate variability and change; and other environmental challenges. As a result of pollution, droughts, more erratic rainfall, heightened demand for water for both consumption and agricultural needs as well as differences in water allocation among the riverine countries of Uganda, Tanzania, Kenya, Rwanda and Burundi, many parts of this region are already experiencing water scarcity on a recurrent basis. Furthermore, given projected annual population growth rates of 2.5 to 3.5% for the next 20 years, water shortages are likely to be exacerbated in the future. Analyzing historical changes in the water resources of this region is hence important to identify "hot spots" that might be most sensitive to future changes in climate and demography. In this presentation, we report the findings of a comprehensive analysis performed to (i) examine changes in water resources of LVB in recent decades and (ii) identify overlap between regions of significant changes in water resources with land cover changes and high population centers that are also projected to grow the fastest over the coming decades. We first utilize several satellite, stations and model(s) based climatic and hydrologic datasets to assess changes in water resources in this region. We then use a quality-controlled Moderate Resolution Imaging Spectroradiometer (MODIS) land cover product to identify areas of significant land cover changes. Simultaneously we use projections of gridded population density based on differential growth rates for rural and urban population to estimate fastest projected human population growth for 2030 and 2050 relative to 2010 data. Using the outcomes of these change analysis we identify water insecurity hotspots in the LVB.

  11. A geostatistical approach to identify and mitigate agricultural nitrous oxide emission hotspots.

    Science.gov (United States)

    Turner, P A; Griffis, T J; Mulla, D J; Baker, J M; Venterea, R T

    2016-12-01

    Anthropogenic emissions of nitrous oxide (N 2 O), a trace gas with severe environmental costs, are greatest from agricultural soils amended with nitrogen (N) fertilizer. However, accurate N 2 O emission estimates at fine spatial scales are made difficult by their high variability, which represents a critical challenge for the management of N 2 O emissions. Here, static chamber measurements (n=60) and soil samples (n=129) were collected at approximately weekly intervals (n=6) for 42-d immediately following the application of N in a southern Minnesota cornfield (15.6-ha), typical of the systems prevalent throughout the U.S. Corn Belt. These data were integrated into a geostatistical model that resolved N 2 O emissions at a high spatial resolution (1-m). Field-scale N 2 O emissions exhibited a high degree of spatial variability, and were partitioned into three classes of emission strength: hotspots, intermediate, and coldspots. Rates of emission from hotspots were 2-fold greater than non-hotspot locations. Consequently, 36% of the field-scale emissions could be attributed to hotspots, despite representing only 21% of the total field area. Variations in elevation caused hotspots to develop in predictable locations, which were prone to nutrient and moisture accumulation caused by terrain focusing. Because these features are relatively static, our data and analyses indicate that targeted management of hotspots could efficiently reduce field-scale emissions by as much 17%, a significant benefit considering the deleterious effects of atmospheric N 2 O. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Identifying Spatio-Temporal Landslide Hotspots on North Island, New Zealand, by Analyzing Historical and Recent Aerial Photography

    Directory of Open Access Journals (Sweden)

    Daniel Hölbling

    2016-11-01

    Full Text Available Accurate mapping of landslides and the reliable identification of areas most affected by landslides are essential for advancing the understanding of landslide erosion processes. Remote sensing data provides a valuable source of information on the spatial distribution and location of landslides. In this paper we present an approach for identifying landslide-prone “hotspots” and their spatio-temporal variability by analyzing historical and recent aerial photography from five different dates, ranging from 1944 to 2011, for a study site near the town of Pahiatua, southeastern North Island, New Zealand. Landslide hotspots are identified from the distribution of semi-automatically detected landslides using object-based image analysis (OBIA, and compared to hotspots derived from manually mapped landslides. When comparing the overlapping areas of the semi-automatically and manually mapped landslides the accuracy values of the OBIA results range between 46% and 61% for the producer’s accuracy and between 44% and 77% for the user’s accuracy. When evaluating whether a manually digitized landslide polygon is only intersected to some extent by any semi-automatically mapped landslide, we observe that for the natural-color images the landslide detection rate is 83% for 2011 and 93% for 2005; for the panchromatic images the values are slightly lower (67% for 1997, 74% for 1979, and 72% for 1944. A comparison of the derived landslide hotspot maps shows that the distribution of the manually identified landslides and those mapped with OBIA is very similar for all periods; though the results also reveal that mapping landslide tails generally requires visual interpretation. Information on the spatio-temporal evolution of landslide hotspots can be useful for the development of location-specific, beneficial intervention measures and for assessing landscape dynamics.

  13. A freshwater biodiversity hotspot under pressure - assessing threats and identifying conservation needs for ancient Lake Ohrid

    Science.gov (United States)

    Kostoski, G.; Albrecht, C.; Trajanovski, S.; Wilke, T.

    2010-12-01

    Immediate conservation measures for world-wide freshwater resources are of eminent importance. This is particularly true for so-called ancient lakes. While these lakes are famous for being evolutionary theatres, often displaying an extraordinarily high degree of biodiversity and endemism, in many cases these biota are also experiencing extreme anthropogenic impact. Lake Ohrid, a major European biodiversity hotspot situated in a trans-frontier setting on the Balkans, is a prime example for a lake with a magnitude of narrow range endemic taxa that are under increasing anthropogenic pressure. Unfortunately, evidence for a "creeping biodiversity crisis" has accumulated over the last decades, and major socio-political changes have gone along with human-mediated environmental changes. Based on field surveys, monitoring data, published records, and expert interviews, we aimed to (1) assess threats to Lake Ohrids' (endemic) biodiversity, (2) summarize existing conservation activities and strategies, and (3) outline future conservation needs for Lake Ohrid. We compiled threats to both specific taxa (and in cases to particular species) as well as to the lake ecosystems itself. Major conservation concerns identified for Lake Ohrid are: (1) watershed impacts, (2) agriculture and forestry, (3) tourism and population growth, (4) non-indigenous species, (5) habitat alteration or loss, (6) unsustainable exploitation of fisheries, and (7) global climate change. Among the major (well-known) threats with high impact are nutrient input (particularly of phosphorus), habitat conversion and silt load. Other threats are potentially of high impact but less well known. Such threats include pollution with hazardous substances (from sources such as mines, former industries, agriculture) or climate change. We review and discuss institutional responsibilities, environmental monitoring and ecosystem management, existing parks and reserves, biodiversity and species measures, international

  14. Eco-Efficient Process Improvement at the Early Development Stage: Identifying Environmental and Economic Process Hotspots for Synergetic Improvement Potential.

    Science.gov (United States)

    Piccinno, Fabiano; Hischier, Roland; Seeger, Stefan; Som, Claudia

    2018-05-15

    We present here a new eco-efficiency process-improvement method to highlight combined environmental and costs hotspots of the production process of new material at a very early development stage. Production-specific and scaled-up results for life cycle assessment (LCA) and production costs are combined in a new analysis to identify synergetic improvement potentials and trade-offs, setting goals for the eco-design of new processes. The identified hotspots and bottlenecks will help users to focus on the relevant steps for improvements from an eco-efficiency perspective and potentially reduce their associated environmental impacts and production costs. Our method is illustrated with a case study of nanocellulose. The results indicate that the production route should start with carrot pomace, use heat and solvent recovery, and deactivate the enzymes with bleach instead of heat. To further improve the process, the results show that focus should be laid on the carrier polymer, sodium alginate, and the production of the GripX coating. Overall, the method shows that the underlying LCA scale-up framework is valuable for purposes beyond conventional LCA studies and is applicable at a very early stage to provide researchers with a better understanding of their production process.

  15. Molecular modeling and docking studies of human 5-hydroxytryptamine 2A (5-HT2A) receptor for the identification of hotspots for ligand binding.

    Science.gov (United States)

    Kanagarajadurai, Karuppiah; Malini, Manoharan; Bhattacharya, Aditi; Panicker, Mitradas M; Sowdhamini, Ramanathan

    2009-12-01

    The serotonergic system has been implicated in emotional and cognitive function. In particular, 5-HT(2A) (5-hydroxytrytamine receptor 2A) is attributed to a number of disorders like schizophrenia, depression, eating disorders and anxiety. 5-HT(2A), being a GPCR (G-protein coupled receptor), is important in the pharmaceutical industry as a proven target for these disorders. Despite their extensive clinical importance, the structural studies of this protein is lacking due to difficulties in determining its crystal structure. We have performed sequence analysis and molecular modeling of 5-HT(2A) that has revealed a set of conserved residues and motifs considered to play an important role in maintaining structural integrity and function of the receptor. The analysis also revealed a set of residues specific to the receptor which distinguishes them from other members of the subclass and their orthologs. Further, starting from the model structure of human 5-HT(2A) receptor, docking studies were attempted to envisage how it might interact with eight of its ligands (such as serotonin, dopamine, DOI, LSD, haloperidol, ketanserin, risperidone and clozapine). The binding studies of dopamine to 5-HT(2A) receptor can bring up better understanding in the etiology of a number of neurological disorders involving both these two receptors. Our sequence analysis and study of interactions of this receptor with other ligands reveal additional residue hotspots such as Asn 363 and Tyr 370. The function of these residues can be further analyzed by rational design of site-directed mutagenesis. Two distinct binding sites are identified which could play important roles in ligand binding and signaling.

  16. Multiple binding modes of ibuprofen in human serum albumin identified by absolute binding free energy calculations

    KAUST Repository

    Evoli, Stefania

    2016-11-10

    Human serum albumin possesses multiple binding sites and transports a wide range of ligands that include the anti-inflammatory drug ibuprofen. A complete map of the binding sites of ibuprofen in albumin is difficult to obtain in traditional experiments, because of the structural adaptability of this protein in accommodating small ligands. In this work, we provide a set of predictions covering the geometry, affinity of binding and protonation state for the pharmaceutically most active form (S-isomer) of ibuprofen to albumin, by using absolute binding free energy calculations in combination with classical molecular dynamics (MD) simulations and molecular docking. The most favorable binding modes correctly reproduce several experimentally identified binding locations, which include the two Sudlow\\'s drug sites (DS2 and DS1) and the fatty acid binding sites 6 and 2 (FA6 and FA2). Previously unknown details of the binding conformations were revealed for some of them, and formerly undetected binding modes were found in other protein sites. The calculated binding affinities exhibit trends which seem to agree with the available experimental data, and drastically degrade when the ligand is modeled in a protonated (neutral) state, indicating that ibuprofen associates with albumin preferentially in its charged form. These findings provide a detailed description of the binding of ibuprofen, help to explain a wide range of results reported in the literature in the last decades, and demonstrate the possibility of using simulation methods to predict ligand binding to albumin.

  17. Hotspots Definition Study

    International Nuclear Information System (INIS)

    De Pater, F.; Brinkman, S.; Schellekens, E.

    2010-03-01

    In the Dutch research programme Climate changes Spatial Planning (CcSP) many scientific projects are carried out. They often take a multidisciplinary approach to the climate issue. However, more attention needed to be given to embedding the programme into practice. Therefore, the board decided to start a hotspot programme. A hotspot was defined as a pilot project in a sector, place or region in which spatial planning and climate change play an important role in the physical shape and land use of the area and where conflicts of interest are found between these and other factors. The hotspot programme started with a definition study. This report is the result of this study. The goal of the study was to identify, describe and evaluate possible hotspots. In two workshops with policy-makers from national and regional governments, consultancy firms and nature conservation organizations, a large number of potential hotspots were identified. Fifteen were selected after the workshops took place and described in detail. The selection was done using a set of conditional criteria, criteria that all had to be met. Two potential hotspots were withdrawn after the selection. Since the Board of the CcSP programme expressed its interest in financing six to seven hotspots, a prioritization was made, using prioritizing criteria. Also the potential hotspots were assessed looking at regional distribution, thematic coverage and target groups. After this assessment and an analysis of the hotspots taking some other factors into account (eg. some hotspots were very similar or one could easily be incorporated in another one) five hotspots were selected: Kampen, Biesbosch-Haringvliet, Zuidplaspolder, Delta Waters and Tilburg. Options to fill the last two places were: Grounds for Change, Noordoostpolder, Oude Vaart Valley and Arnhem/Nijmegen (KAN). For these remaining potential hotspots draft terms of reference were drawn as basis for a project proposals. These terms of reference are added to

  18. Hotspots of missense mutation identify novel neurodevelopmental disorder genes and functional domains

    Science.gov (United States)

    Geisheker, Madeleine R.; Heymann, Gabriel; Wang, Tianyun; Coe, Bradley P.; Turner, Tychele N.; Stessman, Holly A.F.; Hoekzema, Kendra; Kvarnung, Malin; Shaw, Marie; Friend, Kathryn; Liebelt, Jan; Barnett, Christopher; Thompson, Elizabeth M.; Haan, Eric; Guo, Hui; Anderlid, Britt-Marie; Nordgren, Ann; Lindstrand, Anna; Vandeweyer, Geert; Alberti, Antonino; Avola, Emanuela; Vinci, Mirella; Giusto, Stefania; Pramparo, Tiziano; Pierce, Karen; Nalabolu, Srinivasa; Michaelson, Jacob J.; Sedlacek, Zdenek; Santen, Gijs W.E.; Peeters, Hilde; Hakonarson, Hakon; Courchesne, Eric; Romano, Corrado; Kooy, R. Frank; Bernier, Raphael A.; Nordenskjöld, Magnus; Gecz, Jozef; Xia, Kun; Zweifel, Larry S.; Eichler, Evan E.

    2017-01-01

    Although de novo missense mutations have been predicted to account for more cases of autism than gene-truncating mutations, most research has focused on the latter. We identified the properties of de novo missense mutations in patients with neurodevelopmental disorders (NDDs) and highlight 35 genes with excess missense mutations. Additionally, 40 amino acid sites were recurrently mutated in 36 genes, and targeted sequencing of 20 sites in 17,689 NDD patients identified 21 new patients with identical missense mutations. One recurrent site (p.Ala636Thr) occurs in a glutamate receptor subunit, GRIA1. This same amino acid substitution in the homologous but distinct mouse glutamate receptor subunit Grid2 is associated with Lurcher ataxia. Phenotypic follow-up in five individuals with GRIA1 mutations shows evidence of specific learning disabilities and autism. Overall, we find significant clustering of de novo mutations in 200 genes, highlighting specific functional domains and synaptic candidate genes important in NDD pathology. PMID:28628100

  19. Combining Methods to Describe Important Marine Habitats for Top Predators: Application to Identify Biological Hotspots in Tropical Waters.

    Science.gov (United States)

    Thiers, Laurie; Louzao, Maite; Ridoux, Vincent; Le Corre, Matthieu; Jaquemet, Sébastien; Weimerskirch, Henri

    2014-01-01

    In tropical waters resources are usually scarce and patchy, and predatory species generally show specific adaptations for foraging. Tropical seabirds often forage in association with sub-surface predators that create feeding opportunities by bringing prey close to the surface, and the birds often aggregate in large multispecific flocks. Here we hypothesize that frigatebirds, a tropical seabird adapted to foraging with low energetic costs, could be a good predictor of the distribution of their associated predatory species, including other seabirds (e.g. boobies, terns) and subsurface predators (e.g., dolphins, tunas). To test this hypothesis, we compared distribution patterns of marine predators in the Mozambique Channel based on a long-term dataset of both vessel- and aerial surveys, as well as tracking data of frigatebirds. By developing species distribution models (SDMs), we identified key marine areas for tropical predators in relation to contemporaneous oceanographic features to investigate multi-species spatial overlap areas and identify predator hotspots in the Mozambique Channel. SDMs reasonably matched observed patterns and both static (e.g. bathymetry) and dynamic (e.g. Chlorophyll a concentration and sea surface temperature) factors were important explaining predator distribution patterns. We found that the distribution of frigatebirds included the distributions of the associated species. The central part of the channel appeared to be the best habitat for the four groups of species considered in this study (frigatebirds, brown terns, boobies and sub-surface predators).

  20. Combining Methods to Describe Important Marine Habitats for Top Predators: Application to Identify Biological Hotspots in Tropical Waters.

    Directory of Open Access Journals (Sweden)

    Laurie Thiers

    Full Text Available In tropical waters resources are usually scarce and patchy, and predatory species generally show specific adaptations for foraging. Tropical seabirds often forage in association with sub-surface predators that create feeding opportunities by bringing prey close to the surface, and the birds often aggregate in large multispecific flocks. Here we hypothesize that frigatebirds, a tropical seabird adapted to foraging with low energetic costs, could be a good predictor of the distribution of their associated predatory species, including other seabirds (e.g. boobies, terns and subsurface predators (e.g., dolphins, tunas. To test this hypothesis, we compared distribution patterns of marine predators in the Mozambique Channel based on a long-term dataset of both vessel- and aerial surveys, as well as tracking data of frigatebirds. By developing species distribution models (SDMs, we identified key marine areas for tropical predators in relation to contemporaneous oceanographic features to investigate multi-species spatial overlap areas and identify predator hotspots in the Mozambique Channel. SDMs reasonably matched observed patterns and both static (e.g. bathymetry and dynamic (e.g. Chlorophyll a concentration and sea surface temperature factors were important explaining predator distribution patterns. We found that the distribution of frigatebirds included the distributions of the associated species. The central part of the channel appeared to be the best habitat for the four groups of species considered in this study (frigatebirds, brown terns, boobies and sub-surface predators.

  1. Identifying irregularly shaped crime hot-spots using a multiobjective evolutionary algorithm

    Science.gov (United States)

    Wu, Xiaolan; Grubesic, Tony H.

    2010-12-01

    Spatial cluster detection techniques are widely used in criminology, geography, epidemiology, and other fields. In particular, spatial scan statistics are popular and efficient techniques for detecting areas of elevated crime or disease events. The majority of spatial scan approaches attempt to delineate geographic zones by evaluating the significance of clusters using likelihood ratio statistics tested with the Poisson distribution. While this can be effective, many scan statistics give preference to circular clusters, diminishing their ability to identify elongated and/or irregular shaped clusters. Although adjusting the shape of the scan window can mitigate some of these problems, both the significance of irregular clusters and their spatial structure must be accounted for in a meaningful way. This paper utilizes a multiobjective evolutionary algorithm to find clusters with maximum significance while quantitatively tracking their geographic structure. Crime data for the city of Cincinnati are utilized to demonstrate the advantages of the new approach and highlight its benefits versus more traditional scan statistics.

  2. Transcription factor cooperativity in early adipogenic hotspots and super-enhancers

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Rabiee, Atefeh; Nielsen, Ronni

    2014-01-01

    . Using a combination of advanced proteomics and genomics approaches, we identify ∼12,000 transcription factor hotspots (∼400 bp) in the early phase of adipogenesis, and we find evidence of both simultaneous and sequential binding of transcription factors at these regions. We demonstrate that hotspots...

  3. Fine-scale maps of recombination rates and hotspots in the mouse genome.

    Science.gov (United States)

    Brunschwig, Hadassa; Levi, Liat; Ben-David, Eyal; Williams, Robert W; Yakir, Benjamin; Shifman, Sagiv

    2012-07-01

    Recombination events are not uniformly distributed and often cluster in narrow regions known as recombination hotspots. Several studies using different approaches have dramatically advanced our understanding of recombination hotspot regulation. Population genetic data have been used to map and quantify hotspots in the human genome. Genetic variation in recombination rates and hotspots usage have been explored in human pedigrees, mouse intercrosses, and by sperm typing. These studies pointed to the central role of the PRDM9 gene in hotspot modulation. In this study, we used single nucleotide polymorphisms (SNPs) from whole-genome resequencing and genotyping studies of mouse inbred strains to estimate recombination rates across the mouse genome and identified 47,068 historical hotspots--an average of over 2477 per chromosome. We show by simulation that inbred mouse strains can be used to identify positions of historical hotspots. Recombination hotspots were found to be enriched for the predicted binding sequences for different alleles of the PRDM9 protein. Recombination rates were on average lower near transcription start sites (TSS). Comparing the inferred historical recombination hotspots with the recent genome-wide mapping of double-strand breaks (DSBs) in mouse sperm revealed a significant overlap, especially toward the telomeres. Our results suggest that inbred strains can be used to characterize and study the dynamics of historical recombination hotspots. They also strengthen previous findings on mouse recombination hotspots, and specifically the impact of sequence variants in Prdm9.

  4. Identifying Hotspots in Land and Water Resource Uses on the Way towards Achieving the Sustainable Development Goals

    Science.gov (United States)

    Palazzo, A.; Havlik, P.; Van Dijk, M.; Leclere, D.

    2017-12-01

    Agriculture plays a key role in achieving adequate food, water, and energy security (as summarized in the Sustainable Development Goals SDGs) as populations grow and incomes rise. Yet, agriculture is confronted with an enormous challenge to produce more using less. Land and water resources are projected to be strongly affected by climate change demand and agriculture faces growing competition in the demand for these resources. To formulate policies that contribute to achieving the SDGs, policy makers need assessments that can anticipate and navigate the trade-offs within the water/land/energy domain. Assessments that identify locations or hotspots where trade-offs between the multiple, competing users of resources may exist must consider both the local scale impacts of resource use as well as regional scale socioeconomic trends, policies, and international markets that further contribute to or mitigate the impacts of resource trade-offs. In this study, we quantify impacts of increased pressure on the land system to provide agricultural and bioenergy products under increasingly scarce water resources using a global economic and land use model, GLOBIOM. We model the supply and demand of agricultural products at a high spatial resolution in an integrated approach that considers the impacts of global change (socioeconomic and climatic) on the biophysical availability and the growing competition of land and water. We also developed a biodiversity module that relates changes in land uses to changes in local species richness and global species extinction risk. We find that water available for agriculture and freshwater ecosystems decreases due to climate change and growing demand from other sectors (domestic, energy and industry) (Fig 1). Climate change impacts will limit areas suitable for irrigation and may lead to an expansion of rainfed areas in biodiverse areas. Impacts on food security from climate change are significant in some regions (SSA and SA) and policies

  5. Identifying orchid hotspots for biodiversity conservation in Laos: the limestone karst vegetation of Vang Vieng District, Vientiane Province

    Directory of Open Access Journals (Sweden)

    Pankaj Kumar

    2016-10-01

    Full Text Available A project to study the phytodiversity of the Indo-Burma Biodiversity Hotspot (IBBH was initiated by Kadoorie Farm and Botanic Garden, Hong Kong, in 2011, with the aim of surveying primary forest fragments and identifying conservation priorities within this expansive but highly threatened ecoregion. Vang Vieng District of Vientiane Province, northern Laos, was chosen as a focus for a pilot expedition, since it features an extensive karst landscape that has barely been explored. Together with officials from the Ministry of Science and Technology, Government of Lao PDR, surveys of three sites were conducted in April 2012, at the end of the dry northeast monsoon season. Emphasis was placed on Orchidaceae because it is among the most species-rich and commercially exploited flowering plant families in the region. A total of 179 specimens were collected, of which approximately 135 were unique taxa accounting for 29.6% of the orchids found in Laos and 5.8% of those found in IBBH as a whole, and equivalent to 0.27 species/hectare within the area surveyed, substantially higher than published figures for other limestone areas in the region, such as Cuc Phuong National Park in Vietnam (0.0055 species/hectare and Perlis State in Peninsular Malaysia (0.0036 species/hectare.  At least one is a species new to science, nine represent new distributional records for Laos and a further nine are new records for Vientiane Province. A list of the species encountered during the study is presented and the significance of the findings is discussed. Major threats to the natural environment in northern Laos are highlighted.

  6. HIV protein sequence hotspots for crosstalk with host hub proteins.

    Directory of Open Access Journals (Sweden)

    Mahdi Sarmady

    Full Text Available HIV proteins target host hub proteins for transient binding interactions. The presence of viral proteins in the infected cell results in out-competition of host proteins in their interaction with hub proteins, drastically affecting cell physiology. Functional genomics and interactome datasets can be used to quantify the sequence hotspots on the HIV proteome mediating interactions with host hub proteins. In this study, we used the HIV and human interactome databases to identify HIV targeted host hub proteins and their host binding partners (H2. We developed a high throughput computational procedure utilizing motif discovery algorithms on sets of protein sequences, including sequences of HIV and H2 proteins. We identified as HIV sequence hotspots those linear motifs that are highly conserved on HIV sequences and at the same time have a statistically enriched presence on the sequences of H2 proteins. The HIV protein motifs discovered in this study are expressed by subsets of H2 host proteins potentially outcompeted by HIV proteins. A large subset of these motifs is involved in cleavage, nuclear localization, phosphorylation, and transcription factor binding events. Many such motifs are clustered on an HIV sequence in the form of hotspots. The sequential positions of these hotspots are consistent with the curated literature on phenotype altering residue mutations, as well as with existing binding site data. The hotspot map produced in this study is the first global portrayal of HIV motifs involved in altering the host protein network at highly connected hub nodes.

  7. A freshwater biodiversity hotspot under pressure – assessing threats and identifying conservation needs for ancient Lake Ohrid

    Directory of Open Access Journals (Sweden)

    G. Kostoski

    2010-12-01

    Full Text Available Immediate conservation measures for world-wide freshwater resources are of eminent importance. This is particularly true for so-called ancient lakes. While these lakes are famous for being evolutionary theatres, often displaying an extraordinarily high degree of biodiversity and endemism, in many cases these biota are also experiencing extreme anthropogenic impact.

    Lake Ohrid, a major European biodiversity hotspot situated in a trans-frontier setting on the Balkans, is a prime example for a lake with a magnitude of narrow range endemic taxa that are under increasing anthropogenic pressure. Unfortunately, evidence for a "creeping biodiversity crisis" has accumulated over the last decades, and major socio-political changes have gone along with human-mediated environmental changes.

    Based on field surveys, monitoring data, published records, and expert interviews, we aimed to (1 assess threats to Lake Ohrids' (endemic biodiversity, (2 summarize existing conservation activities and strategies, and (3 outline future conservation needs for Lake Ohrid. We compiled threats to both specific taxa (and in cases to particular species as well as to the lake ecosystems itself. Major conservation concerns identified for Lake Ohrid are: (1 watershed impacts, (2 agriculture and forestry, (3 tourism and population growth, (4 non-indigenous species, (5 habitat alteration or loss, (6 unsustainable exploitation of fisheries, and (7 global climate change.

    Among the major (well-known threats with high impact are nutrient input (particularly of phosphorus, habitat conversion and silt load. Other threats are potentially of high impact but less well known. Such threats include pollution with hazardous substances (from sources such as mines, former industries, agriculture or climate change. We review and discuss institutional responsibilities, environmental monitoring and ecosystem management, existing parks and reserves, biodiversity and species

  8. A groundwater salinity hotspot and its connection to an intermittent stream identified by environmental tracers (Mt Lofty Ranges, South Australia)

    Science.gov (United States)

    Anderson, Thomas A.; Bestland, Erick A.; Soloninka, Lesja; Wallis, Ilka; Banks, Edward W.; Pichler, Markus

    2017-12-01

    High and variable levels of salinity were investigated in an intermittent stream in a high-rainfall area (˜800 mm/year) of the Mt. Lofty Ranges of South Australia. The groundwater system was found to have a local, upslope saline lens, referred to here as a groundwater salinity `hotspot'. Environmental tracer analyses (δ18O, δ2H, 87/86Sr, and major elements) of water from the intermittent stream, a nearby permanent stream, shallow and deep groundwater, and soil-water/runoff demonstrate seasonal groundwater input of very saline composition into the intermittent stream. This input results in large salinity increases of the stream water because the winter wet-season stream flow decreases during spring in this Mediterranean climate. Furthermore, strontium and water isotope analyses demonstrate: (1) the upslope-saline-groundwater zone (hotspot) mixes with the dominant groundwater system, (2) the intermittent-stream water is a mixture of soil-water/runoff and the upslope saline groundwater, and (3) the upslope-saline-groundwater zone results from the flushing of unsaturated-zone salts from the thick clayey regolith and soil which overlie the metamorphosed shale bedrock. The preferred theory on the origin of the upslope-saline-groundwater hotspot is land clearing of native deep-rooted woodland, followed by flushing of accumulated salts from the unsaturated zone due to increased recharge. This cause of elevated groundwater and surface-water salinity, if correct, could be widespread in Mt. Lofty Ranges areas, as well as other climatically and geologically similar areas with comparable hydrogeologic conditions.

  9. Sequence requirement of the ade6-4095 meiotic recombination hotspot in Schizosaccharomyces pombe.

    Science.gov (United States)

    Foulis, Steven J; Fowler, Kyle R; Steiner, Walter W

    2018-02-01

    Homologous recombination occurs at a greatly elevated frequency in meiosis compared to mitosis and is initiated by programmed double-strand DNA breaks (DSBs). DSBs do not occur at uniform frequency throughout the genome in most organisms, but occur preferentially at a limited number of sites referred to as hotspots. The location of hotspots have been determined at nucleotide-level resolution in both the budding and fission yeasts, and while several patterns have emerged regarding preferred locations for DSB hotspots, it remains unclear why particular sites experience DSBs at much higher frequency than other sites with seemingly similar properties. Short sequence motifs, which are often sites for binding of transcription factors, are known to be responsible for a number of hotspots. In this study we identified the minimum sequence required for activity of one of such motif identified in a screen of random sequences capable of producing recombination hotspots. The experimentally determined sequence, GGTCTRGACC, closely matches the previously inferred sequence. Full hotspot activity requires an effective sequence length of 9.5 bp, whereas moderate activity requires an effective sequence length of approximately 8.2 bp and shows significant association with DSB hotspots. In combination with our previous work, this result is consistent with a large number of different sequence motifs capable of producing recombination hotspots, and supports a model in which hotspots can be rapidly regenerated by mutation as they are lost through recombination.

  10. Impact of low-frequency hotspot mutation R282Q on the structure of p53 DNA-binding domain as revealed by crystallography at 1.54 Å resolution

    Energy Technology Data Exchange (ETDEWEB)

    Tu, Chao [Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702 (United States); Tan, Yu-Hong [Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697 (United States); Shaw, Gary [Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702 (United States); Zhou, Zheng; Bai, Yawen [Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892 (United States); Luo, Ray [Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, CA 92697 (United States); Ji, Xinhua, E-mail: jix@ncifcrf.gov [Macromolecular Crystallography Laboratory, National Cancer Institute, Frederick, MD 21702 (United States)

    2008-05-01

    The impact of hotspot mutation R282Q on the structure of human p53 DNA-binding domain has been characterized by X-ray crystallography and molecular-dynamics simulations. Tumor suppressor p53 is a sequence-specific DNA-binding protein and its central DNA-binding domain (DBD) harbors six hotspots (Arg175, Gly245, Arg248, Arg249, Arg273 and Arg282) for human cancers. Here, the crystal structure of a low-frequency hotspot mutant, p53DBD(R282Q), is reported at 1.54 Å resolution together with the results of molecular-dynamics simulations on the basis of the structure. In addition to eliminating a salt bridge, the R282Q mutation has a significant impact on the properties of two DNA-binding loops (L1 and L3). The L1 loop is flexible in the wild type, but it is not flexible in the mutant. The L3 loop of the wild type is not flexible, whereas it assumes two conformations in the mutant. Molecular-dynamics simulations indicated that both conformations of the L3 loop are accessible under biological conditions. It is predicted that the elimination of the salt bridge and the inversion of the flexibility of L1 and L3 are directly or indirectly responsible for deactivating the tumor suppressor p53.

  11. Mammalian transcriptional hotspots are enriched for tissue specific enhancers near cell type specific highly expressed genes and are predicted to act as transcriptional activator hubs.

    Science.gov (United States)

    Joshi, Anagha

    2014-12-30

    Transcriptional hotspots are defined as genomic regions bound by multiple factors. They have been identified recently as cell type specific enhancers regulating developmentally essential genes in many species such as worm, fly and humans. The in-depth analysis of hotspots across multiple cell types in same species still remains to be explored and can bring new biological insights. We therefore collected 108 transcription-related factor (TF) ChIP sequencing data sets in ten murine cell types and classified the peaks in each cell type in three groups according to binding occupancy as singletons (low-occupancy), combinatorials (mid-occupancy) and hotspots (high-occupancy). The peaks in the three groups clustered largely according to the occupancy, suggesting priming of genomic loci for mid occupancy irrespective of cell type. We then characterized hotspots for diverse structural functional properties. The genes neighbouring hotspots had a small overlap with hotspot genes in other cell types and were highly enriched for cell type specific function. Hotspots were enriched for sequence motifs of key TFs in that cell type and more than 90% of hotspots were occupied by pioneering factors. Though we did not find any sequence signature in the three groups, the H3K4me1 binding profile had bimodal peaks at hotspots, distinguishing hotspots from mono-modal H3K4me1 singletons. In ES cells, differentially expressed genes after perturbation of activators were enriched for hotspot genes suggesting hotspots primarily act as transcriptional activator hubs. Finally, we proposed that ES hotspots might be under control of SetDB1 and not DNMT for silencing. Transcriptional hotspots are enriched for tissue specific enhancers near cell type specific highly expressed genes. In ES cells, they are predicted to act as transcriptional activator hubs and might be under SetDB1 control for silencing.

  12. Multiple binding modes of ibuprofen in human serum albumin identified by absolute binding free energy calculations

    KAUST Repository

    Evoli, Stefania; Mobley, David L.; Guzzi, Rita; Rizzuti, Bruno

    2016-01-01

    experiments, because of the structural adaptability of this protein in accommodating small ligands. In this work, we provide a set of predictions covering the geometry, affinity of binding and protonation state for the pharmaceutically most active form (S

  13. Methods and systems for identifying ligand-protein binding sites

    KAUST Repository

    Gao, Xin

    2016-05-06

    The invention provides a novel integrated structure and system-based approach for drug target prediction that enables the large-scale discovery of new targets for existing drugs Novel computer-readable storage media and computer systems are also provided. Methods and systems of the invention use novel sequence order-independent structure alignment, hierarchical clustering, and probabilistic sequence similarity techniques to construct a probabilistic pocket ensemble (PPE) that captures even promiscuous structural features of different binding sites for a drug on known targets. The drug\\'s PPE is combined with an approximation of the drug delivery profile to facilitate large-scale prediction of novel drug- protein interactions with several applications to biological research and drug development.

  14. Hotspot advance speed - hotspot size/core-hotspot distance relation ...

    African Journals Online (AJOL)

    We examined the evolution of extragalactic radio sources using the observed corehotspot distance and hotspot size. Analysis indicates a fairly strong positive correlation in the ratio of core-hotspot distance to hotspot size between that of the approaching arm and the receding arm with a correlation coefficient of r ~ 0.7.

  15. Finding trans-regulatory genes and protein complexes modulating meiotic recombination hotspots of human, mouse and yeast.

    Science.gov (United States)

    Wu, Min; Kwoh, Chee-Keong; Li, Xiaoli; Zheng, Jie

    2014-09-11

    The regulatory mechanism of recombination is one of the most fundamental problems in genomics, with wide applications in genome wide association studies (GWAS), birth-defect diseases, molecular evolution, cancer research, etc. Recombination events cluster into short genomic regions called "recombination hotspots". Recently, a zinc finger protein PRDM9 was reported to regulate recombination hotspots in human and mouse genomes. In addition, a 13-mer motif contained in the binding sites of PRDM9 is found to be enriched in human hotspots. However, this 13-mer motif only covers a fraction of hotspots, indicating that PRDM9 is not the only regulator of recombination hotspots. Therefore, the challenge of discovering other regulators of recombination hotspots becomes significant. Furthermore, recombination is a complex process. Hence, multiple proteins acting as machinery, rather than individual proteins, are more likely to carry out this process in a precise and stable manner. Therefore, the extension of the prediction of individual trans-regulators to protein complexes is also highly desired. In this paper, we introduce a pipeline to identify genes and protein complexes associated with recombination hotspots. First, we prioritize proteins associated with hotspots based on their preference of binding to hotspots and coldspots. Second, using the above identified genes as seeds, we apply the Random Walk with Restart algorithm (RWR) to propagate their influences to other proteins in protein-protein interaction (PPI) networks. Hence, many proteins without DNA-binding information will also be assigned a score to implicate their roles in recombination hotspots. Third, we construct sub-PPI networks induced by top genes ranked by RWR for various species (e.g., yeast, human and mouse) and detect protein complexes in those sub-PPI networks. The GO term analysis show that our prioritizing methods and the RWR algorithm are capable of identifying novel genes associated with

  16. Identifying Marine Copper-Binding Ligands in Seawater

    Science.gov (United States)

    Whitby, H.; Hollibaugh, J. T.; Maldonado, M. T.; Ouchi, S.; van den Berg, S. M.

    2016-02-01

    Complexation reactions are important because they affect the bioavailability of trace metals such as copper and iron. For example, organic complexation can determine whether copper is a limiting or a toxic micronutrient at natural levels. Copper competes with iron for complexing ligands, and when iron is limiting, copper can also substitute for iron in some metabolic pathways. The speciation of copper can be measured using complexing capacity titrations, which provide the concentration of individual ligand classes (L1, L2 etc.) and the complex stabilities (log K). Using methods recently developed in our laboratory, we show that the ligands within these classes can be measured independently of titrations, thus confirming the titration method and simultaneously identifying the ligands within each class. Thiols were identified as the L1 ligand class and humic compounds as the weaker L2 class in samples from coastal Georgia, USA, collected monthly from April to December. Log K values of the ligand complexes were consistent with values expected for thiols and humic substances. Recent results from culture studies and from samples collected along Line P, a coastal - oceanic transect in the HNLC region of the NE subarctic Pacific, will be presented in comparison to the estuarine results. This comparison will help to broaden our perspective on copper complexation and the ligands responsible, furthering our understanding of ligand sources and life cycles.

  17. Digging Deeper: Development and evaluation of an untargeted metabolomics approach to identify biogeochemical hotspots with depth and by vegetation type in Arctic tundra soils

    Science.gov (United States)

    Ladd, M.; Wullschleger, S.; Hettich, R.

    2017-12-01

    Elucidating the chemical composition of low molecular weight (LMW) dissolved organic matter (DOM), and monitoring how this bioavailable pool varies over space and time, is critical to understanding the controlling mechanisms that underlie carbon release and storage in Arctic systems. Due to analytical challenges however, relatively little is known about how this complex mixture of small molecules varies with soil depth or how it may be influenced by vegetation. In this study, we evaluated an untargeted metabolomics approach for the characterization of LMW DOM in water extracts, and applied this approach in soil cores (10-cm diam., 30-cm depth), obtained near Barrow, Alaska (71° 16' N) from the organic-rich active layer where the aboveground vegetation was primarily either Carex aquatilis or Eriophorum angustifolium, two species commonly found in tundra systems. We hypothesized that by using a discovery-based approach, spatial patterns of chemical diversity could be identified, enabling the detection of biogeochemical hotspots across scales. LMW DOM profiles from triplicate water extracts were characterized using dual-separation, nano-liquid chromatography (LC) coupled to an electrospray Orbitrap mass spectrometer in positive and negative ion modes. Both LC separations—reversed-phase and hydrophilic interaction chromatography—were achieved with gradient elutions in 15 minutes. Using a precursor and fragment mass measurement accuracy of nutrients) impact carbon fluxes in the Arctic at the landscape-scale.

  18. LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

    KAUST Repository

    Chen, Peng

    2014-12-03

    Background Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction for protein-ligand binding sites, the state-of-the-art methods search for similar, known structures of the query and predict the binding sites based on the solved structures. However, such structural information is not commonly available. Results In this paper, we propose a sequence-based approach to identify protein-ligand binding residues. We propose a combination technique to reduce the effects of different sliding residue windows in the process of encoding input feature vectors. Moreover, due to the highly imbalanced samples between the ligand-binding sites and non ligand-binding sites, we construct several balanced data sets, for each of which a random forest (RF)-based classifier is trained. The ensemble of these RF classifiers forms a sequence-based protein-ligand binding site predictor. Conclusions Experimental results on CASP9 and CASP8 data sets demonstrate that our method compares favorably with the state-of-the-art protein-ligand binding site prediction methods.

  19. Protein Determinants of Meiotic DNA Break Hotspots

    Science.gov (United States)

    Fowler, Kyle R.; Gutiérrez-Velasco, Susana

    2013-01-01

    SUMMARY Meiotic recombination, crucial for proper chromosome segregation and genome evolution, is initiated by programmed DNA double-strand breaks (DSBs) in yeasts and likely all sexually reproducing species. In fission yeast, DSBs occur up to hundreds of times more frequently at special sites, called hotspots, than in other regions of the genome. What distinguishes hotspots from cold regions is an unsolved problem, although transcription factors determine some hotspots. We report the discovery that three coiled-coil proteins – Rec25, Rec27, and Mug20 – bind essentially all hotspots with unprecedented specificity even without DSB formation. These small proteins are components of linear elements, are related to synaptonemal complex proteins, and are essential for nearly all DSBs at most hotspots. Our results indicate these hotspot determinants activate or stabilize the DSB-forming protein Rec12 (Spo11 homolog) rather than promote its binding to hotspots. We propose a new paradigm for hotspot determination and crossover control by linear element proteins. PMID:23395004

  20. Potential ligand-binding residues in rat olfactory receptors identified by correlated mutation analysis

    Science.gov (United States)

    Singer, M. S.; Oliveira, L.; Vriend, G.; Shepherd, G. M.

    1995-01-01

    A family of G-protein-coupled receptors is believed to mediate the recognition of odor molecules. In order to identify potential ligand-binding residues, we have applied correlated mutation analysis to receptor sequences from the rat. This method identifies pairs of sequence positions where residues remain conserved or mutate in tandem, thereby suggesting structural or functional importance. The analysis supported molecular modeling studies in suggesting several residues in positions that were consistent with ligand-binding function. Two of these positions, dominated by histidine residues, may play important roles in ligand binding and could confer broad specificity to mammalian odor receptors. The presence of positive (overdominant) selection at some of the identified positions provides additional evidence for roles in ligand binding. Higher-order groups of correlated residues were also observed. Each group may interact with an individual ligand determinant, and combinations of these groups may provide a multi-dimensional mechanism for receptor diversity.

  1. Challenges in Optimizing a Prostate Carcinoma Binding Peptide, Identified through the Phage Display Technology

    Directory of Open Access Journals (Sweden)

    Jürgen Debus

    2011-02-01

    Full Text Available The transfer of peptides identified through the phage display technology to clinical applications is difficult. Major drawbacks are the metabolic degradation and label instability. The aim of our work is the optimization of DUP-1, a peptide which was identified by phage display to specifically target human prostate carcinoma. To investigate the influence of chelate conjugation, DOTA was coupled to DUP-1 and labeling was performed with 111In. To improve serum stability cyclization of DUP-1 and targeted D-amino acid substitution were carried out. Alanine scanning was performed for identification of the binding site and based on the results peptide fragments were chemically synthesized. The properties of modified ligands were investigated in in vitro binding and competition assays. In vivo biodistribution studies were carried out in mice, carrying human prostate tumors subcutaneously. DOTA conjugation resulted in different cellular binding kinetics, rapid in vivo renal clearance and increased tumor-to-organ ratios. Cyclization and D-amino acid substitution increased the metabolic stability but led to binding affinity decrease. Fragment investigation indicated that the sequence NRAQDY might be significant for target-binding. Our results demonstrate challenges in optimizing peptides, identified through phage display libraries, and show that careful investigation of modified derivatives is necessary in order to improve their characteristics.

  2. Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.

    Directory of Open Access Journals (Sweden)

    Jonathan Göke

    2011-12-01

    Full Text Available Transcription factors are proteins that regulate gene expression by binding to cis-regulatory sequences such as promoters and enhancers. In embryonic stem (ES cells, binding of the transcription factors OCT4, SOX2 and NANOG is essential to maintain the capacity of the cells to differentiate into any cell type of the developing embryo. It is known that transcription factors interact to regulate gene expression. In this study we show that combinatorial binding is strongly associated with co-localization of the transcriptional co-activator Mediator, H3K27ac and increased expression of nearby genes in embryonic stem cells. We observe that the same loci bound by Oct4, Nanog and Sox2 in ES cells frequently drive expression in early embryonic development. Comparison of mouse and human ES cells shows that less than 5% of individual binding events for OCT4, SOX2 and NANOG are shared between species. In contrast, about 15% of combinatorial binding events and even between 53% and 63% of combinatorial binding events at enhancers active in early development are conserved. Our analysis suggests that the combination of OCT4, SOX2 and NANOG binding is critical for transcription in ES cells and likely plays an important role for embryogenesis by binding at conserved early developmental enhancers. Our data suggests that the fast evolutionary rewiring of regulatory networks mainly affects individual binding events, whereas "gene regulatory hotspots" which are bound by multiple factors and active in multiple tissues throughout early development are under stronger evolutionary constraints.

  3. Africa's hotspots of biodiversity redefined

    NARCIS (Netherlands)

    Küper, W.; Sommer, J.H.; Lovett, J.C.; Beentje, H.J.; Rompaey, van R.S.A.R.; Chatelain, C.; Sosef, M.S.M.; Barthlott, W.

    2004-01-01

    A key problem for conservation is the coincidence of regions of high biodiversity with regions of high human impact. Twenty-five of the most threatened centers of plant diversity were identified by Myers et al., and these "hotspots" play a crucial role in international conservation strategies. The

  4. A model-based approach to identify binding sites in CLIP-Seq data.

    Directory of Open Access Journals (Sweden)

    Tao Wang

    Full Text Available Cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-Seq has made it possible to identify the targeting sites of RNA-binding proteins in various cell culture systems and tissue types on a genome-wide scale. Here we present a novel model-based approach (MiClip to identify high-confidence protein-RNA binding sites from CLIP-seq datasets. This approach assigns a probability score for each potential binding site to help prioritize subsequent validation experiments. The MiClip algorithm has been tested in both HITS-CLIP and PAR-CLIP datasets. In the HITS-CLIP dataset, the signal/noise ratios of miRNA seed motif enrichment produced by the MiClip approach are between 17% and 301% higher than those by the ad hoc method for the top 10 most enriched miRNAs. In the PAR-CLIP dataset, the MiClip approach can identify ∼50% more validated binding targets than the original ad hoc method and two recently published methods. To facilitate the application of the algorithm, we have released an R package, MiClip (http://cran.r-project.org/web/packages/MiClip/index.html, and a public web-based graphical user interface software (http://galaxy.qbrc.org/tool_runner?tool_id=mi_clip for customized analysis.

  5. A micro-epidemiological analysis of febrile malaria in Coastal Kenya showing hotspots within hotspots.

    Science.gov (United States)

    Bejon, Philip; Williams, Thomas N; Nyundo, Christopher; Hay, Simon I; Benz, David; Gething, Peter W; Otiende, Mark; Peshu, Judy; Bashraheil, Mahfudh; Greenhouse, Bryan; Bousema, Teun; Bauni, Evasius; Marsh, Kevin; Smith, David L; Borrmann, Steffen

    2014-04-24

    Malaria transmission is spatially heterogeneous. This reduces the efficacy of control strategies, but focusing control strategies on clusters or 'hotspots' of transmission may be highly effective. Among 1500 homesteads in coastal Kenya we calculated (a) the fraction of febrile children with positive malaria smears per homestead, and (b) the mean age of children with malaria per homestead. These two measures were inversely correlated, indicating that children in homesteads at higher transmission acquire immunity more rapidly. This inverse correlation increased gradually with increasing spatial scale of analysis, and hotspots of febrile malaria were identified at every scale. We found hotspots within hotspots, down to the level of an individual homestead. Febrile malaria hotspots were temporally unstable, but 4 km radius hotspots could be targeted for 1 month following 1 month periods of surveillance.DOI: http://dx.doi.org/10.7554/eLife.02130.001. Copyright © 2014, Bejon et al.

  6. Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots.

    Science.gov (United States)

    Baker, Christopher L; Petkova, Pavlina; Walker, Michael; Flachs, Petr; Mihola, Ondrej; Trachtulec, Zdenek; Petkov, Petko M; Paigen, Kenneth

    2015-09-01

    Genetic recombination during meiosis functions to increase genetic diversity, promotes elimination of deleterious alleles, and helps assure proper segregation of chromatids. Mammalian recombination events are concentrated at specialized sites, termed hotspots, whose locations are determined by PRDM9, a zinc finger DNA-binding histone methyltransferase. Prdm9 is highly polymorphic with most alleles activating their own set of hotspots. In populations exhibiting high frequencies of heterozygosity, questions remain about the influences different alleles have in heterozygous individuals where the two variant forms of PRDM9 typically do not activate equivalent populations of hotspots. We now find that, in addition to activating its own hotspots, the presence of one Prdm9 allele can modify the activity of hotspots activated by the other allele. PRDM9 function is also dosage sensitive; Prdm9+/- heterozygous null mice have reduced numbers and less active hotspots and increased numbers of aberrant germ cells. In mice carrying two Prdm9 alleles, there is allelic competition; the stronger Prdm9 allele can partially or entirely suppress chromatin modification and recombination at hotspots of the weaker allele. In cell cultures, PRDM9 protein variants form functional heteromeric complexes which can bind hotspots sequences. When a heteromeric complex binds at a hotspot of one PRDM9 variant, the other PRDM9 variant, which would otherwise not bind, can still methylate hotspot nucleosomes. We propose that in heterozygous individuals the underlying molecular mechanism of allelic suppression results from formation of PRDM9 heteromers, where the DNA binding activity of one protein variant dominantly directs recombination initiation towards its own hotspots, effectively titrating down recombination by the other protein variant. In natural populations with many heterozygous individuals, allelic competition will influence the recombination landscape.

  7. Juvenile hormone-binding proteins of Melanoplus bivittatus identified by EFDA photoaffinity labeling

    International Nuclear Information System (INIS)

    Winder, B.S.

    1988-01-01

    Proteins that bind juvenile hormone in the hemolymph and fat body of the grasshopper, Melanoplus bivittatus were identified by photoaffinity labeling with radiolabeled epoxyfarnesyl diazoacetate ( 3 H-EFDA), and were characterized by electrophoretic analysis. A protocol was developed which allowed detection of 3 H-EFDA that was covalently linked to proteins upon exposure to ultraviolet light at 254 nm. Quantification of protein-linked 3 H-EFDA by liquid scintillation spectrometry took advantage of the differential solubility of unlinked 3 H-EFDA in toluene alone, and of the protein-linked 3 H-EFDA in toluene plus the detergent, Triton X-100. Competition between EFDA and juvenile hormone (JH) for binding to JH-specific binding sites was measured by hydroxyapatite protein binding assays in the presence of radiolabeled JH or EFDA and competing non-radiolabeled hormone. The protein-linked EFDA was detected on fluorograms of SDS or nondenaturing polyacrylamide gels (PAGE), and by liquid scintillation spectrometry of membranes to which the proteins had been electrophoretically transferred. Proteins which specifically bound JH were identified by photolabeling proteins in the presence and absence of nonlabeled JH-III

  8. Molecular docking and NMR binding studies to identify novel inhibitors of human phosphomevalonate kinase

    Energy Technology Data Exchange (ETDEWEB)

    Boonsri, Pornthip [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States); Department of Chemistry, NANOTEC Center of Nanotechnology, National Nanotechnology Center, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Neumann, Terrence S.; Olson, Andrew L.; Cai, Sheng [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States); Herdendorf, Timothy J.; Miziorko, Henry M. [Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110 (United States); Hannongbua, Supa [Department of Chemistry, NANOTEC Center of Nanotechnology, National Nanotechnology Center, Faculty of Science, Kasetsart University, Bangkok 10900 (Thailand); Sem, Daniel S., E-mail: daniel.sem@cuw.edu [Chemical Proteomics Facility at Marquette, Department of Chemistry, Marquette University, Milwaukee, WI 53201 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Natural and synthetic inhibitors of human phosphomevalonate kinase identified. Black-Right-Pointing-Pointer Virtual screening yielded a hit rate of 15%, with inhibitor K{sub d}'s of 10-60 {mu}M. Black-Right-Pointing-Pointer NMR studies indicate significant protein conformational changes upon binding. -- Abstract: Phosphomevalonate kinase (PMK) phosphorylates mevalonate-5-phosphate (M5P) in the mevalonate pathway, which is the sole source of isoprenoids and steroids in humans. We have identified new PMK inhibitors with virtual screening, using autodock. Promising hits were verified and their affinity measured using NMR-based {sup 1}H-{sup 15}N heteronuclear single quantum coherence (HSQC) chemical shift perturbation and fluorescence titrations. Chemical shift changes were monitored, plotted, and fitted to obtain dissociation constants (K{sub d}). Tight binding compounds with K{sub d}'s ranging from 6-60 {mu}M were identified. These compounds tended to have significant polarity and negative charge, similar to the natural substrates (M5P and ATP). HSQC cross peak changes suggest that binding induces a global conformational change, such as domain closure. Compounds identified in this study serve as chemical genetic probes of human PMK, to explore pharmacology of the mevalonate pathway, as well as starting points for further drug development.

  9. Evaluating Temporal Consistency in Marine Biodiversity Hotspots.

    Science.gov (United States)

    Piacenza, Susan E; Thurman, Lindsey L; Barner, Allison K; Benkwitt, Cassandra E; Boersma, Kate S; Cerny-Chipman, Elizabeth B; Ingeman, Kurt E; Kindinger, Tye L; Lindsley, Amy J; Nelson, Jake; Reimer, Jessica N; Rowe, Jennifer C; Shen, Chenchen; Thompson, Kevin A; Heppell, Selina S

    2015-01-01

    With the ongoing crisis of biodiversity loss and limited resources for conservation, the concept of biodiversity hotspots has been useful in determining conservation priority areas. However, there has been limited research into how temporal variability in biodiversity may influence conservation area prioritization. To address this information gap, we present an approach to evaluate the temporal consistency of biodiversity hotspots in large marine ecosystems. Using a large scale, public monitoring dataset collected over an eight year period off the US Pacific Coast, we developed a methodological approach for avoiding biases associated with hotspot delineation. We aggregated benthic fish species data from research trawls and calculated mean hotspot thresholds for fish species richness and Shannon's diversity indices over the eight year dataset. We used a spatial frequency distribution method to assign hotspot designations to the grid cells annually. We found no areas containing consistently high biodiversity through the entire study period based on the mean thresholds, and no grid cell was designated as a hotspot for greater than 50% of the time-series. To test if our approach was sensitive to sampling effort and the geographic extent of the survey, we followed a similar routine for the northern region of the survey area. Our finding of low consistency in benthic fish biodiversity hotspots over time was upheld, regardless of biodiversity metric used, whether thresholds were calculated per year or across all years, or the spatial extent for which we calculated thresholds and identified hotspots. Our results suggest that static measures of benthic fish biodiversity off the US West Coast are insufficient for identification of hotspots and that long-term data are required to appropriately identify patterns of high temporal variability in biodiversity for these highly mobile taxa. Given that ecological communities are responding to a changing climate and other

  10. Substrate Binding Drives Active-Site Closing of Human Blood Group B Galactosyltransferase as Revealed by Hot-Spot Labeling and NMR Spectroscopy Experiments.

    Science.gov (United States)

    Weissbach, Sophie; Flügge, Friedemann; Peters, Thomas

    2018-05-04

    Crystallography has shown that human blood group A (GTA) and B (GTB) glycosyltransferases undergo transitions between "open", "semiclosed", and "closed" conformations upon substrate binding. However, the timescales of the corresponding conformational reorientations are unknown. Crystal structures show that the Trp and Met residues are located at "conformational hot spots" of the enzymes. Therefore, we utilized 15 N side-chain labeling of Trp residues and 13 C-methyl labeling of Met residues to study substrate-induced conformational transitions of GTB. Chemical-shift perturbations (CSPs) of Met and Trp residues in direct contact with substrate ligands reflect binding kinetics, whereas the CSPs of Met and Trp residues at remote sites reflect conformational changes of the enzyme upon substrate binding. Acceptor binding is fast on the chemical-shift timescale with rather small CSPs in the range of less than approximately 20 Hz. Donor binding matches the intermediate exchange regime to yield an estimate for exchange rate constants of approximately 200-300 Hz. Donor or acceptor binding to GTB saturated with acceptor or donor substrate, respectively, is slow (<10 Hz), as are coupled protein motions, reflecting mutual allosteric control of donor and acceptor binding. Remote CSPs suggest that substrate binding drives the enzyme into the closed state required for catalysis. These findings should contribute to better understanding of the mechanism of glycosyl transfer of GTA and GTB. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Dynamic malaria hotspots in an open cohort in western Kenya.

    Science.gov (United States)

    Platt, Alyssa; Obala, Andrew A; MacIntyre, Charlie; Otsyula, Barasa; Meara, Wendy Prudhomme O'

    2018-01-12

    Malaria hotspots, defined as areas where transmission intensity exceeds the average level, become more pronounced as transmission declines. Targeting hotspots may accelerate reductions in transmission and could be pivotal for malaria elimination. Determinants of hotspot location, particularly of their movement, are poorly understood. We used spatial statistical methods to identify foci of incidence of self-reported malaria in a large census population of 64,000 people, in 8,290 compounds over a 2.5-year study period. Regression models examine stability of hotspots and identify static and dynamic correlates with their location. Hotspot location changed over short time-periods, rarely recurring in the same area. Hotspots identified in spring versus fall season differed in their stability. Households located in a hotspot in the fall were more likely to be located in a hotspot the following fall (RR = 1.77, 95% CI: 1.66-1.89), but the opposite was true for compounds in spring hotspots (RR = 0.15, 95% CI: 0.08-0.28). Location within a hotspot was related to environmental and static household characteristics such as distance to roads or rivers. Human migration into a household was correlated with risk of hotspot membership, but the direction of the association differed based on the origin of the migration event.

  12. FANCD2 binding identifies conserved fragile sites at large transcribed genes in avian cells

    DEFF Research Database (Denmark)

    Pentzold, Constanze; Shah, Shiraz Ali; Hansen, Niels Richard

    2018-01-01

    Common Chromosomal Fragile Sites (CFSs) are specific genomic regions prone to form breaks on metaphase chromosomes in response to replication stress. Moreover, CFSs are mutational hotspots in cancer genomes, showing that the mutational mechanisms that operate at CFSs are highly active in cancer c...

  13. Taksonomi i et hotspot

    DEFF Research Database (Denmark)

    Balslev, Henrik

    2016-01-01

    Op mod halvdelen af alle jordens plantearter findes koncentreret på kun 1,4 % af jordoverfladen. Langt de fleste af disse hotspots for biodiversitet befinder sig i de tropiske egne, hvor vores viden om antallet af arter er mangelfuld. Thailand er placeret i centrum af jordens største hotspot, som...

  14. LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

    KAUST Repository

    Chen, Peng; Huang, Jianhua Z; Gao, Xin

    2014-01-01

    Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction

  15. The Ebola virus VP35 protein binds viral immunostimulatory and host RNAs identified through deep sequencing.

    Directory of Open Access Journals (Sweden)

    Kari A Dilley

    Full Text Available Ebola virus and Marburg virus are members of the Filovirdae family and causative agents of hemorrhagic fever with high fatality rates in humans. Filovirus virulence is partially attributed to the VP35 protein, a well-characterized inhibitor of the RIG-I-like receptor pathway that triggers the antiviral interferon (IFN response. Prior work demonstrates the ability of VP35 to block potent RIG-I activators, such as Sendai virus (SeV, and this IFN-antagonist activity is directly correlated with its ability to bind RNA. Several structural studies demonstrate that VP35 binds short synthetic dsRNAs; yet, there are no data that identify viral immunostimulatory RNAs (isRNA or host RNAs bound to VP35 in cells. Utilizing a SeV infection model, we demonstrate that both viral isRNA and host RNAs are bound to Ebola and Marburg VP35s in cells. By deep sequencing the purified VP35-bound RNA, we identified the SeV copy-back defective interfering (DI RNA, previously identified as a robust RIG-I activator, as the isRNA bound by multiple filovirus VP35 proteins, including the VP35 protein from the West African outbreak strain (Makona EBOV. Moreover, RNAs isolated from a VP35 RNA-binding mutant were not immunostimulatory and did not include the SeV DI RNA. Strikingly, an analysis of host RNAs bound by wild-type, but not mutant, VP35 revealed that select host RNAs are preferentially bound by VP35 in cell culture. Taken together, these data support a model in which VP35 sequesters isRNA in virus-infected cells to avert RIG-I like receptor (RLR activation.

  16. The Ebola virus VP35 protein binds viral immunostimulatory and host RNAs identified through deep sequencing.

    Science.gov (United States)

    Dilley, Kari A; Voorhies, Alexander A; Luthra, Priya; Puri, Vinita; Stockwell, Timothy B; Lorenzi, Hernan; Basler, Christopher F; Shabman, Reed S

    2017-01-01

    Ebola virus and Marburg virus are members of the Filovirdae family and causative agents of hemorrhagic fever with high fatality rates in humans. Filovirus virulence is partially attributed to the VP35 protein, a well-characterized inhibitor of the RIG-I-like receptor pathway that triggers the antiviral interferon (IFN) response. Prior work demonstrates the ability of VP35 to block potent RIG-I activators, such as Sendai virus (SeV), and this IFN-antagonist activity is directly correlated with its ability to bind RNA. Several structural studies demonstrate that VP35 binds short synthetic dsRNAs; yet, there are no data that identify viral immunostimulatory RNAs (isRNA) or host RNAs bound to VP35 in cells. Utilizing a SeV infection model, we demonstrate that both viral isRNA and host RNAs are bound to Ebola and Marburg VP35s in cells. By deep sequencing the purified VP35-bound RNA, we identified the SeV copy-back defective interfering (DI) RNA, previously identified as a robust RIG-I activator, as the isRNA bound by multiple filovirus VP35 proteins, including the VP35 protein from the West African outbreak strain (Makona EBOV). Moreover, RNAs isolated from a VP35 RNA-binding mutant were not immunostimulatory and did not include the SeV DI RNA. Strikingly, an analysis of host RNAs bound by wild-type, but not mutant, VP35 revealed that select host RNAs are preferentially bound by VP35 in cell culture. Taken together, these data support a model in which VP35 sequesters isRNA in virus-infected cells to avert RIG-I like receptor (RLR) activation.

  17. NIMS: hotspots on Io during G2

    Science.gov (United States)

    1996-01-01

    The Near Infrared Mapping Spectrometer (NIMS) on the Galileo spacecraft imaged Io at high spectral resolution at a range of 439,000 km (275,000 miles) during the G2 encounter on 7 September 1996. This image shows (on the right) Io as seen in the infrared by NIMS. The image on the left shows the same view from Voyager in 1979. This NIMS image can be compared to the NIMS images from the G1 orbit (June 1996) to monitor changes on Io. The NIMS image is at 4.9 microns, showing thermal emissions from the hotspots. The brightness of the pixels is a function of size and temperature.At least 10 hotspots have been identified and can be matched with surface features. An accurate determination of the position of the hotspot in the vicinity of Shamash Patera is pending. Hotspots are seen in the vicinity of Prometheus, Volund and Marduk, all sites of volcanic plume activity during the Galileo encounters, and also of active plumes in 1979. Temperatures and areas have been calculated for the hotspots shown. Temperatures range from 828 K (1031 F) to 210 K (- 81.4 F). The lowest temperature is significantly higher than the Io background (non-hotspot) surface temperature of about 100 K (-279 F). Hotspot areas range from 6.5 square km (2.5 sq miles) to 40,000 sq km (15,400 sq miles). The hottest hotspots have smallest areas, and the cooler hotspots have the largest areas. NIMS is continuing to observe Io to monitor volcanic activity throughout the Galileo mission.The Galileo mission is managed by the Jet Propulsion Laboratory for NASA's Office of Space Science, Washington, D.C.This image and other images and data received from Galileo are posted on the Galileo mission home page on the World Wide Web at http://galileo.jpl.nasa.gov.

  18. LDsplit: screening for cis-regulatory motifs stimulating meiotic recombination hotspots by analysis of DNA sequence polymorphisms.

    Science.gov (United States)

    Yang, Peng; Wu, Min; Guo, Jing; Kwoh, Chee Keong; Przytycka, Teresa M; Zheng, Jie

    2014-02-17

    As a fundamental genomic element, meiotic recombination hotspot plays important roles in life sciences. Thus uncovering its regulatory mechanisms has broad impact on biomedical research. Despite the recent identification of the zinc finger protein PRDM9 and its 13-mer binding motif as major regulators for meiotic recombination hotspots, other regulators remain to be discovered. Existing methods for finding DNA sequence motifs of recombination hotspots often rely on the enrichment of co-localizations between hotspots and short DNA patterns, which ignore the cross-individual variation of recombination rates and sequence polymorphisms in the population. Our objective in this paper is to capture signals encoded in genetic variations for the discovery of recombination-associated DNA motifs. Recently, an algorithm called "LDsplit" has been designed to detect the association between single nucleotide polymorphisms (SNPs) and proximal meiotic recombination hotspots. The association is measured by the difference of population recombination rates at a hotspot between two alleles of a candidate SNP. Here we present an open source software tool of LDsplit, with integrative data visualization for recombination hotspots and their proximal SNPs. Applying LDsplit on SNPs inside an established 7-mer motif bound by PRDM9 we observed that SNP alleles preserving the original motif tend to have higher recombination rates than the opposite alleles that disrupt the motif. Running on SNP windows around hotspots each containing an occurrence of the 7-mer motif, LDsplit is able to guide the established motif finding algorithm of MEME to recover the 7-mer motif. In contrast, without LDsplit the 7-mer motif could not be identified. LDsplit is a software tool for the discovery of cis-regulatory DNA sequence motifs stimulating meiotic recombination hotspots by screening and narrowing down to hotspot associated SNPs. It is the first computational method that utilizes the genetic variation of

  19. A computational tool to predict the evolutionarily conserved protein-protein interaction hot-spot residues from the structure of the unbound protein.

    Science.gov (United States)

    Agrawal, Neeraj J; Helk, Bernhard; Trout, Bernhardt L

    2014-01-21

    Identifying hot-spot residues - residues that are critical to protein-protein binding - can help to elucidate a protein's function and assist in designing therapeutic molecules to target those residues. We present a novel computational tool, termed spatial-interaction-map (SIM), to predict the hot-spot residues of an evolutionarily conserved protein-protein interaction from the structure of an unbound protein alone. SIM can predict the protein hot-spot residues with an accuracy of 36-57%. Thus, the SIM tool can be used to predict the yet unknown hot-spot residues for many proteins for which the structure of the protein-protein complexes are not available, thereby providing a clue to their functions and an opportunity to design therapeutic molecules to target these proteins. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  20. Lsa63, a newly identified surface protein of Leptospira interrogans binds laminin and collagen IV.

    Science.gov (United States)

    Vieira, Monica L; de Morais, Zenaide M; Gonçales, Amane P; Romero, Eliete C; Vasconcellos, Silvio A; Nascimento, Ana L T O

    2010-01-01

    Leptospira interrogans is the etiological agent of leptospirosis, a zoonotic disease that affects populations worldwide. We have identified in proteomic studies a protein that is encoded by the gene LIC10314 and expressed in virulent strain of L. interrogans serovar Pomona. This protein was predicted to be surface exposed by PSORT program and contains a p83/100 domain identified by BLAST analysis that is conserved in protein antigens of several strains of Borrelia and Treponema spp. The proteins containing this domain have been claimed antigen candidates for serodiagnosis of Lyme borreliosis. Thus, we have cloned the LIC10314 and expressed the protein in Escherichia coli BL21-SI strain by using the expression vector pAE. The recombinant protein tagged with N-terminal hexahistidine was purified by metal-charged chromatography and characterized by circular dichroism spectroscopy. This protein is conserved among several species of pathogenic Leptospira and absent in the saprophytic strain L. biflexa. We confirm by liquid-phase immunofluorescence assays with living organisms that this protein is most likely a new surface leptospiral protein. The ability of the protein to mediate attachment to ECM components was evaluated by binding assays. The leptospiral protein encoded by LIC10314, named Lsa63 (Leptospiral surface adhesin of 63kDa), binds strongly to laminin and collagen IV in a dose-dependent and saturable fashion. In addition, Lsa63 is probably expressed during infection since it was recognized by antibodies of serum samples of confirmed-leptospirosis patients in convalescent phase of the disease. Altogether, the data suggests that this novel identified surface protein may be involved in leptospiral pathogenesis. 2009 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

  1. Unraveling a Hotspot for TCR Recognition on HLA-A2: Evidence Against the Existence of Peptide-independent TCR Binding Determinants

    International Nuclear Information System (INIS)

    Gagnon, Susan J.; Borbulevych, Oleg Y.; Davis-Harrison, Rebecca L.; Baxter, Tiffany K.; Clemens, John R.; Armstrong, Kathryn M.; Turner, Richard V.; Damirjian, Marale; Biddison, William E.; Baker, Brian M.

    2005-01-01

    T cell receptor (TCR) recognition of peptide takes place in the context of the major histocompatibility complex (MHC) molecule, which accounts for approximately two-thirds of the peptide/MHC buried surface. Using the class I MHC HLA-A2 and a large panel of mutants, we have previously shown that surface mutations that disrupt TCR recognition vary with the identity of the peptide. The single exception is Lys66 on the HLA-A2 α1 helix, which when mutated to alanine disrupts recognition for 93% of over 250 different T cell clones or lines, independent of which peptide is bound. Thus, Lys66 could serve as a peptide-independent TCR binding determinant. Here, we have examined the role of Lys66 in TCR recognition of HLA-A2 in detail. The structure of a peptide/HLA-A2 molecule with the K66A mutation indicates that although the mutation induces no major structural changes, it results in the exposure of a negatively charged glutamate (Glu63) underneath Lys66. Concurrent replacement of Glu63 with glutamine restores TCR binding and function for T cells specific for five different peptides presented by HLA-A2. Thus, the positive charge on Lys66 does not serve to guide all TCRs onto the HLA-A2 molecule in a manner required for productive signaling. Furthermore, electrostatic calculations indicate that Lys66 does not contribute to the stability of two TCR-peptide/HLA-A2 complexes. Our findings are consistent with the notion that each TCR arrives at a unique solution of how to bind a peptide/MHC, most strongly influenced by the chemical and structural features of the bound peptide. This would not rule out an intrinsic affinity of TCRs for MHC molecules achieved through multiple weak interactions, but for HLA-A2 the collective mutational data place limits on the role of any single MHC amino acid side-chain in driving TCR binding in a peptide-independent fashion.

  2. Allele frequencies of variants in ultra conserved elements identify selective pressure on transcription factor binding.

    Directory of Open Access Journals (Sweden)

    Toomas Silla

    Full Text Available Ultra-conserved genes or elements (UCGs/UCEs in the human genome are extreme examples of conservation. We characterized natural variations in 2884 UCEs and UCGs in two distinct populations; Singaporean Chinese (n = 280 and Italian (n = 501 by using a pooled sample, targeted capture, sequencing approach. We identify, with high confidence, in these regions the abundance of rare SNVs (MAF5% are more often found in relatively less-conserved nucleotides within UCEs, compared to rare variants. Moreover, prevalent variants are less likely to overlap transcription factor binding site. Using SNPfold we found no significant influence of RNA secondary structure on UCE conservation. All together, these results suggest UCEs are not under selective pressure as a stretch of DNA but are under differential evolutionary pressure on the single nucleotide level.

  3. Allele frequencies of variants in ultra conserved elements identify selective pressure on transcription factor binding.

    Science.gov (United States)

    Silla, Toomas; Kepp, Katrin; Tai, E Shyong; Goh, Liang; Davila, Sonia; Catela Ivkovic, Tina; Calin, George A; Voorhoeve, P Mathijs

    2014-01-01

    Ultra-conserved genes or elements (UCGs/UCEs) in the human genome are extreme examples of conservation. We characterized natural variations in 2884 UCEs and UCGs in two distinct populations; Singaporean Chinese (n = 280) and Italian (n = 501) by using a pooled sample, targeted capture, sequencing approach. We identify, with high confidence, in these regions the abundance of rare SNVs (MAFpower for association studies. By combining our data with 1000 Genome Project data, we show in three independent datasets that prevalent UCE variants (MAF>5%) are more often found in relatively less-conserved nucleotides within UCEs, compared to rare variants. Moreover, prevalent variants are less likely to overlap transcription factor binding site. Using SNPfold we found no significant influence of RNA secondary structure on UCE conservation. All together, these results suggest UCEs are not under selective pressure as a stretch of DNA but are under differential evolutionary pressure on the single nucleotide level.

  4. A fluorescence polarization binding assay to identify inhibitors of flavin-dependent monooxygenases.

    Science.gov (United States)

    Qi, Jun; Kizjakina, Karina; Robinson, Reeder; Tolani, Karishma; Sobrado, Pablo

    2012-06-01

    N-Hydroxylating monooxygenases (NMOs) are essential for pathogenesis in fungi and bacteria. NMOs catalyze the hydroxylation of sine and ornithine in the biosynthesis of hydroxamate-containing siderophores. Inhibition of kynurenine monooxygenase (KMO), which catalyzes the conversion of kynurenine to 3-hydroxykynurenine, alleviates neurodegenerative disorders such as Huntington's and Alzheimer's diseases and brain infections caused by the parasite Trypanosoma brucei. These enzymes are examples of flavin-dependent monooxygenases, which are validated drug targets. Here, we describe the development and optimization of a fluorescence polarization assay to identify potential inhibitors of flavin-dependent monooxygenases. Fluorescently labeled ADP molecules were synthesized and tested. An ADP-TAMRA chromophore bound to KMO with a K(d) value of 0.60 ± 0.05 μM and to the NMOs from Aspergillus fumigatus and Mycobacterium smegmatis with K(d) values of 2.1 ± 0.2 and 4.0 ± 0.2 μM, respectively. The assay was tested in competitive binding experiments with substrates and products of KMO and an NMO. Furthermore, we show that this assay can be used to identify inhibitors of NMOs. A Z' factor of 0.77 was calculated, and we show that the assay exhibits good tolerance to temperature, incubation time, and dimethyl sulfoxide concentration. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Warfare in biodiversity hotspots.

    Science.gov (United States)

    Hanson, Thor; Brooks, Thomas M; Da Fonseca, Gustavo A B; Hoffmann, Michael; Lamoreux, John F; Machlis, Gary; Mittermeier, Cristina G; Mittermeier, Russell A; Pilgrim, John D

    2009-06-01

    Conservation efforts are only as sustainable as the social and political context within which they take place. The weakening or collapse of sociopolitical frameworks during wartime can lead to habitat destruction and the erosion of conservation policies, but in some cases, may also confer ecological benefits through altered settlement patterns and reduced resource exploitation. Over 90% of the major armed conflicts between 1950 and 2000 occurred within countries containing biodiversity hotspots, and more than 80% took place directly within hotspot areas. Less than one-third of the 34 recognized hotspots escaped significant conflict during this period, and most suffered repeated episodes of violence. This pattern was remarkably consistent over these 5 decades. Evidence from the war-torn Eastern Afromontane hotspot suggests that biodiversity conservation is improved when international nongovernmental organizations support local protected area staff and remain engaged throughout the conflict. With biodiversity hotspots concentrated in politically volatile regions, the conservation community must maintain continuous involvement during periods of war, and biodiversity conservation should be incorporated into military, reconstruction, and humanitarian programs in the world's conflict zones. ©2009 Society for Conservation Biology.

  6. Modeling Resource Hotspots: Critical Linkages and Processes

    Science.gov (United States)

    Daher, B.; Mohtar, R.; Pistikopoulos, E.; McCarl, B. A.; Yang, Y.

    2017-12-01

    Growing demands for interconnected resources emerge in the form of hotspots of varying characteristics. The business as usual allocation model cannot address the current, let alone anticipated, complex and highly interconnected resource challenges we face. A new paradigm for resource allocation must be adopted: one that identifies cross-sectoral synergies and, that moves away from silos to recognition of the nexus and integration of it. Doing so will result in new opportunities for business growth, economic development, and improved social well-being. Solutions and interventions must be multi-faceted; opportunities should be identified with holistic trade-offs in mind. No single solution fits all: different hotspots will require distinct interventions. Hotspots have varying resource constraints, stakeholders, goals and targets. The San Antonio region represents a complex resource hotspot with promising potential: its rapidly growing population, the Eagle Ford shale play, and the major agricultural activity there makes it a hotspot with many competing demands. Stakeholders need tools to allow them to knowledgeably address impending resource challenges. This study will identify contemporary WEF nexus questions and critical system interlinkages that will inform the modeling of the tightly interconnected resource systems and stresses using the San Antonio Region as a base; it will conceptualize a WEF nexus modeling framework, and develop assessment criteria to inform integrative planning and decision making.

  7. Structures of the Apo and FAD-bound forms of 2-hydroxybiphenyl 3-monooxygenase (HbpA) locate activity hotspots identified by using directed evolution.

    Science.gov (United States)

    Jensen, Chantel N; Mielke, Tamara; Farrugia, Joseph E; Frank, Annika; Man, Henry; Hart, Sam; Turkenburg, Johan P; Grogan, Gideon

    2015-04-13

    The FAD-dependent monooxygenase HbpA from Pseudomonas azelaica HBP1 catalyses the hydroxylation of 2-hydroxybiphenyl (2HBP) to 2,3-dihydroxybiphenyl (23DHBP). HbpA has been used extensively as a model for studying flavoprotein hydroxylases under process conditions, and has also been subjected to directed-evolution experiments that altered its catalytic properties. The structure of HbpA has been determined in its apo and FAD-complex forms to resolutions of 2.76 and 2.03 Å, respectively. Comparisons of the HbpA structure with those of homologues, in conjunction with a model of the reaction product in the active site, reveal His48 as the most likely acid/base residue to be involved in the hydroxylation mechanism. Mutation of His48 to Ala resulted in an inactive enzyme. The structures of HbpA also provide evidence that mutants achieved by directed evolution that altered activity are comparatively remote from the substrate-binding site. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Hotspot swells revisited

    Science.gov (United States)

    King, Scott D.; Adam, Claudia

    2014-10-01

    The first attempts to quantify the width and height of hotspot swells were made more than 30 years ago. Since that time, topography, ocean-floor age, and sediment thickness datasets have improved considerably. Swell heights and widths have been used to estimate the heat flow from the core-mantle boundary, constrain numerical models of plumes, and as an indicator of the origin of hotspots. In this paper, we repeat the analysis of swell geometry and buoyancy flux for 54 hotspots, including the 37 considered by Sleep (1990) and the 49 considered by Courtillot et al. (2003), using the latest and most accurate data. We are able to calculate swell geometry for a number of hotspots that Sleep was only able to estimate by comparison with other swells. We find that in spite of the increased resolution in global bathymetry models there is significant uncertainty in our calculation of buoyancy fluxes due to differences in our measurement of the swells’ width and height, the integration method (volume integration or cross-sectional area), and the variations of the plate velocities between HS2-Nuvel1a (Gripp and Gordon, 1990) and HS3-Nuvel1a (Gripp and Gordon, 2002). We also note that the buoyancy flux for Pacific hotspots is in general larger than for Eurasian, North American, African and Antarctic hotspots. Considering that buoyancy flux is linearly related to plate velocity, we speculate that either the calculation of buoyancy flux using plate velocity over-estimates the actual vertical flow of material from the deep mantle or that convection in the Pacific hemisphere is more vigorous than the Atlantic hemisphere.

  9. Distinct forms of the β subunit of GTP-binding regulatory proteins identified by molecular cloning

    International Nuclear Information System (INIS)

    Fong, H.K.W.; Amatruda, T.T. III; Birren, B.W.; Simon, M.I.

    1987-01-01

    Two distinct β subunits of guanine nucleotide-binding regulatory proteins have been identified by cDNA cloning and are referred to as β 1 and β 1 subunits. The bovine transducin β subunit (β 1 ) has been cloned previously. The author now isolated and analyzed cDNA clones that encode the β 2 subunit from bovine adrenal, bovine brain, and a human myeloid leukemia cell line, HL-60. The 340-residue M/sub r/ 37,329 Β 2 protein is 90% identical with β 1 in predicted amino acid sequence, and it is also organized as a series of repetitive homologous segments. The major mRNA that encodes the bovine β 2 subunit is 1.7 kilobases in length. It is expressed at lower levels than β 1 subunit mRNA in all tissues examined. The β 1 and β 2 messages are expressed in cloned human cell lines. Hybridization of cDNA probes to bovine DNA showed that β 1 and β 2 are encoded by separate genes. The amino acid sequences for the bovine and human β 2 subunit are identical, as are the amino acid sequences for the bovine and human β 1 subunit. This evolutionary conservation suggests that the two β subunits have different roles in the signal transduction process

  10. A newly identified protein of Leptospira interrogans mediates binding to laminin.

    Science.gov (United States)

    Longhi, Mariana T; Oliveira, Tatiane R; Romero, Eliete C; Gonçales, Amane P; de Morais, Zenaide M; Vasconcellos, Silvio A; Nascimento, Ana L T O

    2009-10-01

    Pathogenic Leptospira is the aetiological agent of leptospirosis, a life-threatening disease that affects populations worldwide. The search for novel antigens that could be relevant in host-pathogen interactions is being pursued. These antigens have the potential to elicit several activities, including adhesion. This study focused on a hypothetical predicted lipoprotein of Leptospira, encoded by the gene LIC12895, thought to mediate attachment to extracellular matrix (ECM) components. The gene was cloned and expressed in Escherichia coli BL21 Star (DE3)pLys by using the expression vector pAE. The recombinant protein tagged with N-terminal hexahistidine was purified by metal-charged chromatography and characterized by circular dichroism spectroscopy. The capacity of the protein to mediate attachment to ECM components was evaluated by binding assays. The leptospiral protein encoded by LIC12895, named Lsa27 (leptospiral surface adhesin, 27 kDa), bound strongly to laminin in a dose-dependent and saturable fashion. Moreover, Lsa27 was recognized by antibodies from serum samples of confirmed leptospirosis specimens in both the initial and the convalescent phases of the disease. Lsa27 is most likely a surface protein of Leptospira as revealed in liquid-phase immunofluorescence assays with living organisms. Taken together, these data indicate that this newly identified membrane protein is expressed during natural infection and may play a role in mediating adhesion of L. interrogans to its host.

  11. Characterization and Prediction of Protein Phosphorylation Hotspots in Arabidopsis thaliana.

    Science.gov (United States)

    Christian, Jan-Ole; Braginets, Rostyslav; Schulze, Waltraud X; Walther, Dirk

    2012-01-01

    The regulation of protein function by modulating the surface charge status via sequence-locally enriched phosphorylation sites (P-sites) in so called phosphorylation "hotspots" has gained increased attention in recent years. We set out to identify P-hotspots in the model plant Arabidopsis thaliana. We analyzed the spacing of experimentally detected P-sites within peptide-covered regions along Arabidopsis protein sequences as available from the PhosPhAt database. Confirming earlier reports (Schweiger and Linial, 2010), we found that, indeed, P-sites tend to cluster and that distributions between serine and threonine P-sites to their respected closest next P-site differ significantly from those for tyrosine P-sites. The ability to predict P-hotspots by applying available computational P-site prediction programs that focus on identifying single P-sites was observed to be severely compromised by the inevitable interference of nearby P-sites. We devised a new approach, named HotSPotter, for the prediction of phosphorylation hotspots. HotSPotter is based primarily on local amino acid compositional preferences rather than sequence position-specific motifs and uses support vector machines as the underlying classification engine. HotSPotter correctly identified experimentally determined phosphorylation hotspots in A. thaliana with high accuracy. Applied to the Arabidopsis proteome, HotSPotter-predicted 13,677 candidate P-hotspots in 9,599 proteins corresponding to 7,847 unique genes. Hotspot containing proteins are involved predominantly in signaling processes confirming the surmised modulating role of hotspots in signaling and interaction events. Our study provides new bioinformatics means to identify phosphorylation hotspots and lays the basis for further investigating novel candidate P-hotspots. All phosphorylation hotspot annotations and predictions have been made available as part of the PhosPhAt database at http://phosphat.mpimp-golm.mpg.de.

  12. Evolutionary hotspots in the Mojave Desert

    Science.gov (United States)

    Vandergast, Amy G.; Inman, Richard D.; Barr, Kelly R.; Nussear, Kenneth E.; Esque, Todd C.; Hathaway, Stacie A.; Wood, Dustin A.; Medica, Philip A.; Breinholt, Jesse W.; Stephen, Catherine L.; Gottscho, Andrew D.; Marks, Sharyn B.; Jennings, W. Bryan; Fisher, Robert N.

    2013-01-01

    Genetic diversity within species provides the raw material for adaptation and evolution. Just as regions of high species diversity are conservation targets, identifying regions containing high genetic diversity and divergence within and among populations may be important to protect future evolutionary potential. When multiple co-distributed species show spatial overlap in high genetic diversity and divergence, these regions can be considered evolutionary hotspots. We mapped spatial population genetic structure for 17 animal species across the Mojave Desert, USA. We analyzed these in concurrence and located 10 regions of high genetic diversity, divergence or both among species. These were mainly concentrated along the western and southern boundaries where ecotones between mountain, grassland and desert habitat are prevalent, and along the Colorado River. We evaluated the extent to which these hotspots overlapped protected lands and utility-scale renewable energy development projects of the Bureau of Land Management. While 30–40% of the total hotspot area was categorized as protected, between 3–7% overlapped with proposed renewable energy project footprints, and up to 17% overlapped with project footprints combined with transmission corridors. Overlap of evolutionary hotspots with renewable energy development mainly occurred in 6 of the 10 identified hotspots. Resulting GIS-based maps can be incorporated into ongoing landscape planning efforts and highlight specific regions where further investigation of impacts to population persistence and genetic connectivity may be warranted.

  13. NHS-Esters As Versatile Reactivity-Based Probes for Mapping Proteome-Wide Ligandable Hotspots.

    Science.gov (United States)

    Ward, Carl C; Kleinman, Jordan I; Nomura, Daniel K

    2017-06-16

    Most of the proteome is considered undruggable, oftentimes hindering translational efforts for drug discovery. Identifying previously unknown druggable hotspots in proteins would enable strategies for pharmacologically interrogating these sites with small molecules. Activity-based protein profiling (ABPP) has arisen as a powerful chemoproteomic strategy that uses reactivity-based chemical probes to map reactive, functional, and ligandable hotspots in complex proteomes, which has enabled inhibitor discovery against various therapeutic protein targets. Here, we report an alkyne-functionalized N-hydroxysuccinimide-ester (NHS-ester) as a versatile reactivity-based probe for mapping the reactivity of a wide range of nucleophilic ligandable hotspots, including lysines, serines, threonines, and tyrosines, encompassing active sites, allosteric sites, post-translational modification sites, protein interaction sites, and previously uncharacterized potential binding sites. Surprisingly, we also show that fragment-based NHS-ester ligands can be made to confer selectivity for specific lysine hotspots on specific targets including Dpyd, Aldh2, and Gstt1. We thus put forth NHS-esters as promising reactivity-based probes and chemical scaffolds for covalent ligand discovery.

  14. Characterization of the Raf kinase inhibitory protein (RKIP) binding pocket: NMR-based screening identifies small-molecule ligands.

    Science.gov (United States)

    Shemon, Anne N; Heil, Gary L; Granovsky, Alexey E; Clark, Mathew M; McElheny, Dan; Chimon, Alexander; Rosner, Marsha R; Koide, Shohei

    2010-05-05

    Raf kinase inhibitory protein (RKIP), also known as phoshaptidylethanolamine binding protein (PEBP), has been shown to inhibit Raf and thereby negatively regulate growth factor signaling by the Raf/MAP kinase pathway. RKIP has also been shown to suppress metastasis. We have previously demonstrated that RKIP/Raf interaction is regulated by two mechanisms: phosphorylation of RKIP at Ser-153, and occupation of RKIP's conserved ligand binding domain with a phospholipid (2-dihexanoyl-sn-glycero-3-phosphoethanolamine; DHPE). In addition to phospholipids, other ligands have been reported to bind this domain; however their binding properties remain uncharacterized. In this study, we used high-resolution heteronuclear NMR spectroscopy to screen a chemical library and assay a number of potential RKIP ligands for binding to the protein. Surprisingly, many compounds previously postulated as RKIP ligands showed no detectable binding in near-physiological solution conditions even at millimolar concentrations. In contrast, we found three novel ligands for RKIP that specifically bind to the RKIP pocket. Interestingly, unlike the phospholipid, DHPE, these newly identified ligands did not affect RKIP binding to Raf-1 or RKIP phosphorylation. One out of the three ligands displayed off target biological effects, impairing EGF-induced MAPK and metabolic activity. This work defines the binding properties of RKIP ligands under near physiological conditions, establishing RKIP's affinity for hydrophobic ligands and the importance of bulky aliphatic chains for inhibiting its function. The common structural elements of these compounds defines a minimal requirement for RKIP binding and thus they can be used as lead compounds for future design of RKIP ligands with therapeutic potential.

  15. Characterization of the Raf kinase inhibitory protein (RKIP binding pocket: NMR-based screening identifies small-molecule ligands.

    Directory of Open Access Journals (Sweden)

    Anne N Shemon

    2010-05-01

    Full Text Available Raf kinase inhibitory protein (RKIP, also known as phoshaptidylethanolamine binding protein (PEBP, has been shown to inhibit Raf and thereby negatively regulate growth factor signaling by the Raf/MAP kinase pathway. RKIP has also been shown to suppress metastasis. We have previously demonstrated that RKIP/Raf interaction is regulated by two mechanisms: phosphorylation of RKIP at Ser-153, and occupation of RKIP's conserved ligand binding domain with a phospholipid (2-dihexanoyl-sn-glycero-3-phosphoethanolamine; DHPE. In addition to phospholipids, other ligands have been reported to bind this domain; however their binding properties remain uncharacterized.In this study, we used high-resolution heteronuclear NMR spectroscopy to screen a chemical library and assay a number of potential RKIP ligands for binding to the protein. Surprisingly, many compounds previously postulated as RKIP ligands showed no detectable binding in near-physiological solution conditions even at millimolar concentrations. In contrast, we found three novel ligands for RKIP that specifically bind to the RKIP pocket. Interestingly, unlike the phospholipid, DHPE, these newly identified ligands did not affect RKIP binding to Raf-1 or RKIP phosphorylation. One out of the three ligands displayed off target biological effects, impairing EGF-induced MAPK and metabolic activity.This work defines the binding properties of RKIP ligands under near physiological conditions, establishing RKIP's affinity for hydrophobic ligands and the importance of bulky aliphatic chains for inhibiting its function. The common structural elements of these compounds defines a minimal requirement for RKIP binding and thus they can be used as lead compounds for future design of RKIP ligands with therapeutic potential.

  16. Bayesian inference of shared recombination hotspots between humans and chimpanzees.

    Science.gov (United States)

    Wang, Ying; Rannala, Bruce

    2014-12-01

    Recombination generates variation and facilitates evolution. Recombination (or lack thereof) also contributes to human genetic disease. Methods for mapping genes influencing complex genetic diseases via association rely on linkage disequilibrium (LD) in human populations, which is influenced by rates of recombination across the genome. Comparative population genomic analyses of recombination using related primate species can identify factors influencing rates of recombination in humans. Such studies can indicate how variable hotspots for recombination may be both among individuals (or populations) and over evolutionary timescales. Previous studies have suggested that locations of recombination hotspots are not conserved between humans and chimpanzees. We made use of the data sets from recent resequencing projects and applied a Bayesian method for identifying hotspots and estimating recombination rates. We also reanalyzed SNP data sets for regions with known hotspots in humans using samples from the human and chimpanzee. The Bayes factors (BF) of shared recombination hotspots between human and chimpanzee across regions were obtained. Based on the analysis of the aligned regions of human chromosome 21, locations where the two species show evidence of shared recombination hotspots (with high BFs) were identified. Interestingly, previous comparative studies of human and chimpanzee that focused on the known human recombination hotspots within the β-globin and HLA regions did not find overlapping of hotspots. Our results show high BFs of shared hotspots at locations within both regions, and the estimated locations of shared hotspots overlap with the locations of human recombination hotspots obtained from sperm-typing studies. Copyright © 2014 by the Genetics Society of America.

  17. Penicillin-binding proteins of Escherichia coli identified with a 125I-derivative of ampicillin

    International Nuclear Information System (INIS)

    Schwarz, U.; Seeger, K.; Wengenmayer, F.; Strecker, H.

    1981-01-01

    Evaluation of the binding of β-lactam antibiotics to penicillin-binding proteins (PBPs) in the bacterial cell wall by the established method using 14 C-labelled penicillin G has some disadvantages. Due to the small number of PBP molecules and the relatively low specific activity of [ 14 C]penicillin G available, very long exposure times for autoradiography are required. Furthermore, additional radiolabelled derivatives of penicillin with modified binding patterns might reveal PBPs not known so far. The authors describe the synthesis of a 125 I-labelled derivative of ampicillin and the labelling of PBPs with this compound. (Auth.)

  18. Hotspots in Hindsight

    Science.gov (United States)

    Julian, B. R.; Foulger, G. R.; Hatfield, O.; Jackson, S.; Simpson, E.; Einbeck, J.; Moore, A.

    2014-12-01

    Torsvik et al. [2006] suggest that the original locations of large igneous provinces ("LIPs") and kimberlites, and current locations of melting anomalies (hot-spots) lie preferentially above the margins of two Large Lower-Mantle Shear Velocity Provinces" (LLSVPs), at the base of the mantle, and that the correlation has a high significance level (> 99.9999%). They conclude the LLSVP margins are Plume-Generation Zones, and deep-mantle plumes cause hotspots and LIPs. This conclusion raises questions about what physical processes could be responsible, because, for example the LLSVPs are likely dense and not abnormally hot [Trampert et al., 2004]. The supposed LIP-hotspot-LLSVP correlations probably are examples of the "Hindsight Heresy" [Acton, 1959], of basing a statistical test upon the same data sample that led to the initial formulation of a hypothesis. In doing this, many competing hypotheses will have been considered and rejected, but this fact will not be taken into account in statistical assessments. Furthermore, probabilities will be computed for many subsets and combinations of the data, and the best-correlated cases will be cited, but this fact will not be taken into account either. Tests using independent hot-spot catalogs and mantle models suggest that the actual significance levels of the correlations are two or three orders of magnitude smaller than claimed. These tests also show that hot spots correlate well with presumably shallowly rooted features such as spreading plate boundaries. Consideration of the kimberlite dataset in the context of geological setting suggests that their apparent association with the LLSVP margins results from the fact that the Kaapvaal craton, the site of most of the kimberlites considered, lies in Southern Africa. These observations raise questions about the distinction between correlation and causation and underline the necessity to take geological factors into account. Fig: Left: Cumulative distributions of distances from

  19. Identifying functional transcription factor binding sites in yeast by considering their positional preference in the promoters.

    Directory of Open Access Journals (Sweden)

    Fu-Jou Lai

    Full Text Available Transcription factor binding site (TFBS identification plays an important role in deciphering gene regulatory codes. With comprehensive knowledge of TFBSs, one can understand molecular mechanisms of gene regulation. In the recent decades, various computational approaches have been proposed to predict TFBSs in the genome. The TFBS dataset of a TF generated by each algorithm is a ranked list of predicted TFBSs of that TF, where top ranked TFBSs are statistically significant ones. However, whether these statistically significant TFBSs are functional (i.e. biologically relevant is still unknown. Here we develop a post-processor, called the functional propensity calculator (FPC, to assign a functional propensity to each TFBS in the existing computationally predicted TFBS datasets. It is known that functional TFBSs reveal strong positional preference towards the transcriptional start site (TSS. This motivates us to take TFBS position relative to the TSS as the key idea in building our FPC. Based on our calculated functional propensities, the TFBSs of a TF in the original TFBS dataset could be reordered, where top ranked TFBSs are now the ones with high functional propensities. To validate the biological significance of our results, we perform three published statistical tests to assess the enrichment of Gene Ontology (GO terms, the enrichment of physical protein-protein interactions, and the tendency of being co-expressed. The top ranked TFBSs in our reordered TFBS dataset outperform the top ranked TFBSs in the original TFBS dataset, justifying the effectiveness of our post-processor in extracting functional TFBSs from the original TFBS dataset. More importantly, assigning functional propensities to putative TFBSs enables biologists to easily identify which TFBSs in the promoter of interest are likely to be biologically relevant and are good candidates to do further detailed experimental investigation. The FPC is implemented as a web tool at http://santiago.ee.ncku.edu.tw/FPC/.

  20. Using Remote Sensing and High-Resolution Digital Elevation Models to Identify Potential Erosional Hotspots Along River Channels During High Discharge Storm Events

    Science.gov (United States)

    Orland, E. D.; Amidon, W. H.

    2017-12-01

    As global warming intensifies, large precipitation events and associated floods are becoming increasingly common. Channel adjustments during floods can occur by both erosion and deposition of sediment, often damaging infrastructure in the process. There is thus a need for predictive models that can help managers identify river reaches that are most prone to adjustment during storms. Because rivers in post-glacial landscapes often flow over a mixture of bedrock and alluvial substrates, the identification of bedrock vs. alluvial channel reaches is an important first step in predicting vulnerability to channel adjustment during flood events, especially because bedrock channels are unlikely to adjust significantly, even during floods. This study develops a semi-automated approach to predicting channel substrate using a high-resolution LiDAR-derived digital elevation model (DEM). The study area is the Middlebury River in Middlebury, VT-a well-studied watershed with a wide variety of channel substrates, including reaches with documented channel adjustments during recent flooding events. Multiple metrics were considered for reference—such as channel width and drainage area—but the study utilized channel slope as a key parameter for identifying morphological variations within the Middlebury River. Using data extracted from the DEM, a power law was fit to selected slope and drainage area values for each branch in order to model idealized slope-drainage area relationships, which were then compared with measured slope-drainage area relationships. Differences in measured slope minus predicted slope (called delta-slope) are shown to help predict river channel substrate. Compared with field observations, higher delta-slope values correlate with more stable, boulder rich channels or bedrock gorges; conversely the lowest delta-slope values correlate with flat, sediment rich alluvial channels. The delta-slope metric thus serves as a reliable first-order predictor of channel

  1. Human population in the biodiversity hotspots.

    Science.gov (United States)

    Cincotta, R P; Wisnewski, J; Engelman, R

    2000-04-27

    Biologists have identified 25 areas, called biodiversity hotspots, that are especially rich in endemic species and particularly threatened by human activities. The human population dynamics of these areas, however, are not well quantified. Here we report estimates of key demographic variables for each hotspot, and for three extensive tropical forest areas that are less immediately threatened. We estimate that in 1995 more than 1.1 billion people, nearly 20% of world population, were living within the hotspots, an area covering about 12% of Earth's terrestrial surface. We estimate that the population growth rate in the hotspots (1995-2000) is 1.8% yr(-1), substantially higher than the population growth rate of the world as a whole (1.3% yr(-1)) and above that of the developing countries (1.6% yr(-1)). These results suggest that substantial human-induced environmental changes are likely to continue in the hotspots and that demographic change remains an important factor in global biodiversity conservation. The results also underline the potential conservation significance of the continuing worldwide declines in human fertility and of policies and programs that influence human migration.

  2. Neuropeptide Y binding sites in rat brain identified with purified neuropeptide Y-I125

    International Nuclear Information System (INIS)

    Walker, M.W.; Miller, R.J.

    1986-01-01

    Neuropeptide Y (NPY) is a widely distributed neuronally localized peptide with 36 amino acids, 5 of which are tyrosines. The authors wished to investigate the properties of specific receptors for NPY. They therefore labeled the tyrosines with I125 using chloramine T and then purified the peptide using HPLC. A single mono-iodinated species of NPY which yielded > 85% specific binding in rat forebrain synaptosomes was selected as the ligand for all subsequent experiments. A time course of binding showed that equilibrium conditions were reached in 60 minutes at 21 0 C. Scatchard plots revealed a single class of binding sites with a Kd and a Bmax of 3 x 10-10 M and 28 pmol/mg, respectively. Competition binding with unlabeled NPY showed 50% displacement of bound ligand at 1 x 10-10 M NPY. Competition binding with rat pancreatic polypeptide (RPP), a homologous peptide possessing little NPY-like activity, showed 50% displacement of bound ligand at 2 x 10 -7 M RPP. No binding was observed on F-11 or PC12 neuronal cell lines, or on HSWP fibroblast cells. They conclude that NPY-I125 purified to homogeneity with HPLC is a highly selective ligand for NPY receptor sites. They are currently investigating such sites in brain, gut, and other tissues

  3. Seed plant features, distribution patterns, diversity hotspots, and conservation gaps in Xinjiang, China

    Directory of Open Access Journals (Sweden)

    Jihong Huang

    2018-06-01

    Full Text Available The flora in Xinjiang is unique. Decisions about biodiversity conservation and management based on seed plant diversity hotspots and conservation gaps in Xinjiang are essential to maintain this unique flora. Based on a species distribution dataset of seed plants, we measured seed plant diversity using species richness and phylogenetic diversity indices. Five percent of Xinjiang’s total land area with the highest biodiversity was used to identify hotspots for each index. In total, eight hotspots were identified. Most hotspots were located in mountainous areas, mainly in the Tianshan Mountains and Altai Mountains. Furthermore, we detected conservation gaps for Xinjiang’s seed flora hotspots by overlaying nature reserve maps on to maps of identified hotspots and we designated priority conservation gaps for hotspots by overlaying global biodiversity hotspot maps on to hotspot conservation gaps maps. Most of Xinjiang’s seed plant hotspots are poorly protected; only 10.45% of these hotspots were covered by nature reserves. We suggest that it is essential to promote network function of nature reserves within these hotspots in Xinjiang to conserve this unique flora.

  4. Identifying conservation hotspots using tillage erosion modeling

    Science.gov (United States)

    Tillage operations redistribute soil within agricultural landscapes due to deviations in the quantity of soil moved during tillage. Tillage erosion is the net loss or accumulation of soil at any spot within an agricultural landscape due to soil being directly moved by tillage; it is a dominant erosi...

  5. Characteristics of suicide hotspots on the Belgian railway network.

    Science.gov (United States)

    Debbaut, Kevin; Krysinska, Karolina; Andriessen, Karl

    2014-01-01

    In 2004, railway suicide accounted for 5.3% of all suicides in Belgium. In 2008, Infrabel (Manager of the Belgian Railway Infrastructure) introduced a railway suicide prevention programme, including identification of suicide hotspots, i.e., areas of the railway network with an elevated incidence of suicide. The study presents an analysis of 43 suicide hotspots based on Infrabel data collected during field visits and semi-structured interviews conducted in mental health facilities in the vicinity of the hotspots. Three major characteristics of the hotspots were accessibility, anonymity, and vicinity of a mental health institution. The interviews identified several risk and protective factors for railway suicide, including the training of staff, introduction of a suicide prevention policy, and the role of the media. In conclusion, a comprehensive railway suicide prevention programme should continuously safeguard and monitor hotspots, and should be embedded in a comprehensive suicide prevention programme in the community.

  6. Yeast one-hybrid system used to identify the binding proteins for rat glutathione S-transferase P enhancer I.

    Science.gov (United States)

    Liao, Ming-Xiang; Liu, Dong-Yuan; Zuo, Jin; Fang, Fu-De

    2002-03-01

    To detect the trans-factors specifically binding to the strong enhancer element (GPEI) in the upstream of rat glutathione S-transferase P (GST-P) gene. Yeast one-hybrid system was used to screen rat lung MATCHMAKER cDNA library to identify potential trans-factors that can interact with core sequence of GPEI(cGPEI). Electrophoresis mobility shift assay (EMSA) was used to analyze the binding of transfactors to cGPEI. cDNA fragments coding for the C-terminal part of the transcription factor c-Jun and rat adenine nucleotide translocator (ANT) were isolated. The binding of c-Jun and ANT to GPEI core sequence were confirmed. Rat c-jun transcriptional factor and ANT may interact with cGPEI. They could play an important role in the induced expression of GST-P gene.

  7. A Phenotypic Cell-Binding Screen Identifies a Novel Compound Targeting Triple-Negative Breast Cancer.

    Science.gov (United States)

    Chen, Luxi; Long, Chao; Youn, Jonghae; Lee, Jiyong

    2018-06-11

    We describe a "phenotypic cell-binding screen" by which therapeutic candidate targeting cancer cells of a particular phenotype can be isolated without knowledge of drug targets. Chemical library beads are incubated with cancer cells of the phenotype of interest in the presence of cancer cells lacking the phenotype of interest, and then the beads bound to only cancer cells of the phenotype of interest are selected as hits. We have applied this screening strategy in discovering a novel compound (LC129-8) targeting triple-negative breast cancer (TNBC). LC129-8 displayed highly specific binding to TNBC in cancer cell lines and patient-derived tumor tissues. LC129-8 exerted anti-TNBC activity by inducing apoptosis, inhibiting proliferation, reversing epithelial-mesenchymal transition, downregulating cancer stem cell activity and blocking in vivo tumor growth.

  8. A protein-binding domain, EH, identified in the receptor tyrosine kinase substrate Eps15 and conserved in evolution

    DEFF Research Database (Denmark)

    Wong, W T; Schumacher, C; Salcini, A E

    1995-01-01

    In this report we structurally and functionally define a binding domain that is involved in protein association and that we have designated EH (for Eps15 homology domain). This domain was identified in the tyrosine kinase substrate Eps15 on the basis of regional conservation with several heteroge......In this report we structurally and functionally define a binding domain that is involved in protein association and that we have designated EH (for Eps15 homology domain). This domain was identified in the tyrosine kinase substrate Eps15 on the basis of regional conservation with several...... heterogeneous proteins of yeast and nematode. The EH domain spans about 70 amino acids and shows approximately 60% overall amino acid conservation. We demonstrated the ability of the EH domain to specifically bind cytosolic proteins in normal and malignant cells of mesenchymal, epithelial, and hematopoietic...... (for Eps15-related). Structural comparison of Eps15 and Eps15r defines a family of signal transducers possessing extensive networking abilities including EH-mediated binding and association with Src homology 3-containing proteins....

  9. Geopolitical hotspots : Saudi Arabia

    International Nuclear Information System (INIS)

    Roberts, J.

    2004-01-01

    This presentation reviewed the geopolitics of energy in the Middle East, with particular reference to Saudi Arabia as a potential hotspot. The author examined the question of who actually governs Saudi Arabia and the core relationship between Crown Prince Abdullah and the interior Minister, Prince Nayef. Issues regarding the country's social stability were discussed with reference to the high unemployment rate. The financial security of Saudi Arabia was also discussed with reference to the need for economic and political reform. Expectations for Saudi petroleum output were outlined along with regional spurs for energy competition and OPEC participation

  10. NIMS Observation of Hotspots on Io

    Science.gov (United States)

    1996-01-01

    Io has been imaged by the Near Infrared Mapping Spectrometer (NIMS) on Galileo. The image on the right shows for the first time the distribution of volcanic hotspots on the surface of Io, as seen by NIMS. Three of these hotspots are new discoveries, only detectable with the NIMS instrument. This image was taken during the G1 encounter on June 29 1996. The image on the left shows the same view of Io as seen by the Voyager spacecraft in 1979. At least one dozen hotspots have been identified from this NIMS image. Most of the hotspot locations can be matched with volcanic features on the surface of Io, including the vent area of the active Prometheus plume.The Jet Propulsion Laboratory, Pasadena, CA manages the mission for NASA's Office of Space Science, Washington, DC.This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://galileo.jpl.nasa.gov.

  11. PRDM9 drives evolutionary erosion of hotspots in Mus musculus through haplotype-specific initiation of meiotic recombination.

    Science.gov (United States)

    Baker, Christopher L; Kajita, Shimpei; Walker, Michael; Saxl, Ruth L; Raghupathy, Narayanan; Choi, Kwangbom; Petkov, Petko M; Paigen, Kenneth

    2015-01-01

    Meiotic recombination generates new genetic variation and assures the proper segregation of chromosomes in gametes. PRDM9, a zinc finger protein with histone methyltransferase activity, initiates meiotic recombination by binding DNA at recombination hotspots and directing the position of DNA double-strand breaks (DSB). The DSB repair mechanism suggests that hotspots should eventually self-destruct, yet genome-wide recombination levels remain constant, a conundrum known as the hotspot paradox. To test if PRDM9 drives this evolutionary erosion, we measured activity of the Prdm9Cst allele in two Mus musculus subspecies, M.m. castaneus, in which Prdm9Cst arose, and M.m. domesticus, into which Prdm9Cst was introduced experimentally. Comparing these two strains, we find that haplotype differences at hotspots lead to qualitative and quantitative changes in PRDM9 binding and activity. Using Mus spretus as an outlier, we found most variants affecting PRDM9Cst binding arose and were fixed in M.m. castaneus, suppressing hotspot activity. Furthermore, M.m. castaneus×M.m. domesticus F1 hybrids exhibit novel hotspots, with large haplotype biases in both PRDM9 binding and chromatin modification. These novel hotspots represent sites of historic evolutionary erosion that become activated in hybrids due to crosstalk between one parent's Prdm9 allele and the opposite parent's chromosome. Together these data support a model where haplotype-specific PRDM9 binding directs biased gene conversion at hotspots, ultimately leading to hotspot erosion.

  12. Genome wide association identifies common variants at the SERPINA6/SERPINA1 locus influencing plasma cortisol and corticosteroid binding globulin.

    Directory of Open Access Journals (Sweden)

    Jennifer L Bolton

    2014-07-01

    Full Text Available Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma, and SERPINA1, encoding α1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG. Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136 influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.

  13. Identifying Conformational-Selection and Induced-Fit Aspects in the Binding-Induced Folding of PMI from Markov State Modeling of Atomistic Simulations.

    Science.gov (United States)

    Paul, Fabian; Noé, Frank; Weikl, Thomas R

    2018-03-27

    Unstructured proteins and peptides typically fold during binding to ligand proteins. A challenging problem is to identify the mechanism and kinetics of these binding-induced folding processes in experiments and atomistic simulations. In this Article, we present a detailed picture for the folding of the inhibitor peptide PMI into a helix during binding to the oncoprotein fragment 25-109 Mdm2 obtained from atomistic, explicit-water simulations and Markov state modeling. We find that binding-induced folding of PMI is highly parallel and can occur along a multitude of pathways. Some pathways are induced-fit-like with binding occurring prior to PMI helix formation, while other pathways are conformational-selection-like with binding after helix formation. On the majority of pathways, however, binding is intricately coupled to folding, without clear temporal ordering. A central feature of these pathways is PMI motion on the Mdm2 surface, along the binding groove of Mdm2 or over the rim of this groove. The native binding groove of Mdm2 thus appears as an asymmetric funnel for PMI binding. Overall, binding-induced folding of PMI does not fit into the classical picture of induced fit or conformational selection that implies a clear temporal ordering of binding and folding events. We argue that this holds in general for binding-induced folding processes because binding and folding events in these processes likely occur on similar time scales and do exhibit the time-scale separation required for temporal ordering.

  14. Modelling Hotspots for Invasive Alien Plants in India.

    Science.gov (United States)

    Adhikari, Dibyendu; Tiwary, Raghuvar; Barik, Saroj Kanta

    2015-01-01

    Identification of invasion hotspots that support multiple invasive alien species (IAS) is a pre-requisite for control and management of invasion. However, till recently it remained a methodological challenge to precisely determine such invasive hotspots. We identified the hotspots of alien species invasion in India through Ecological Niche Modelling (ENM) using species occurrence data from the Global Biodiversity Information Facility (GBIF). The predicted area of invasion for selected species were classified into 4 categories based on number of model agreements for a region i.e. high, medium, low and very low. About 49% of the total geographical area of India was predicted to be prone to invasion at moderate to high levels of climatic suitability. The intersection of anthropogenic biomes and ecoregions with the regions of 'high' climatic suitability was classified as hotspot of alien plant invasion. Nineteen of 47 ecoregions of India, harboured such hotspots. Most ecologically sensitive regions of India, including the 'biodiversity hotspots' and coastal regions coincide with invasion hotspots, indicating their vulnerability to alien plant invasion. Besides demonstrating the usefulness of ENM and open source data for IAS management, the present study provides a knowledge base for guiding the formulation of an effective policy and management strategy for controlling the invasive alien species.

  15. Consensus of sample-balanced classifiers for identifying ligand-binding residue by co-evolutionary physicochemical characteristics of amino acids

    KAUST Repository

    Chen, Peng

    2013-01-01

    Protein-ligand binding is an important mechanism for some proteins to perform their functions, and those binding sites are the residues of proteins that physically bind to ligands. So far, the state-of-the-art methods search for similar, known structures of the query and predict the binding sites based on the solved structures. However, such structural information is not commonly available. In this paper, we propose a sequence-based approach to identify protein-ligand binding residues. Due to the highly imbalanced samples between the ligand-binding sites and non ligand-binding sites, we constructed several balanced data sets, for each of which a random forest (RF)-based classifier was trained. The ensemble of these RF classifiers formed a sequence-based protein-ligand binding site predictor. Experimental results on CASP9 targets demonstrated that our method compared favorably with the state-of-the-art. © Springer-Verlag Berlin Heidelberg 2013.

  16. PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans.

    Science.gov (United States)

    Berg, Ingrid L; Neumann, Rita; Lam, Kwan-Wood G; Sarbajna, Shriparna; Odenthal-Hesse, Linda; May, Celia A; Jeffreys, Alec J

    2010-10-01

    PRDM9 has recently been identified as a likely trans regulator of meiotic recombination hot spots in humans and mice. PRDM9 contains a zinc finger array that, in humans, can recognize a short sequence motif associated with hot spots, with binding to this motif possibly triggering hot-spot activity via chromatin remodeling. We now report that human genetic variation at the PRDM9 locus has a strong effect on sperm hot-spot activity, even at hot spots lacking the sequence motif. Subtle changes within the zinc finger array can create hot-spot nonactivating or enhancing variants and can even trigger the appearance of a new hot spot, suggesting that PRDM9 is a major global regulator of hot spots in humans. Variation at the PRDM9 locus also influences aspects of genome instability-specifically, a megabase-scale rearrangement underlying two genomic disorders as well as minisatellite instability-implicating PRDM9 as a risk factor for some pathological genome rearrangements.

  17. High-throughput sequencing enhanced phage display identifies peptides that bind mycobacteria

    CSIR Research Space (South Africa)

    Ngubane, NAC

    2013-11-01

    Full Text Available . The displayed peptides are flanked by two cysteine residues, which are oxidized during phage assembly to a disulfide bond, resulting in a loop constrained peptide. We initially used the traditional clone picking method to identify the enriched clones... of the library, 1.236109 heptapeptides, it represented sufficient depth to measure the quantitative enrich- ment of relevant peptides. To confirm successful enrichment during selection, we characterized the reduction in diversity of the pool in the consecutive...

  18. The Manihiki Plateau—a key to missing hotspot tracks?

    Science.gov (United States)

    Pietsch, R.; Uenzelmann-Neben, G.

    2016-08-01

    A Neogene magmatic reactivation of the Manihiki Plateau, a large igneous province (LIP) in the central Pacific, is studied using seismic reflection data. Igneous diapirs have been identified exclusively within a narrow WNW-ESE striking corridor in the southern High Plateau (HP), which is parallel to the Neogene Pacific Plate motion and overlaps with an extrapolation of the Society Islands Hotspot (SIH) path. The igneous diapirs are characterized by a narrow width (>5 km), penetration of the Neogene sediments, and they become progressively younger towards the East (23-10 Ma). The magmatic source appears to be of small lateral extent, which leads to the conclusion that the diapirs represent Neogene hotspot volcanism within a LIP, and thus may be an older, previously unknown extension of the SIH track (>4.5 Ma). Comparing hotspot volcanism within oceanic and continental lithosphere, we further conclude that hotspot volcanism within LIP crust has similarities to tectonically faulted continental crust.

  19. Fragment library screening identifies hits that bind to the non-catalytic surface of Pseudomonas aeruginosa DsbA1

    Science.gov (United States)

    Headey, Stephen J.; Vazirani, Mansha; Shouldice, Stephen R.; Coinçon, Mathieu; Tay, Stephanie; Morton, Craig J.; Simpson, Jamie S.; Martin, Jennifer L.

    2017-01-01

    At a time when the antibiotic drug discovery pipeline has stalled, antibiotic resistance is accelerating with catastrophic implications for our ability to treat bacterial infections. Globally we face the prospect of a future when common infections can once again kill. Anti-virulence approaches that target the capacity of the bacterium to cause disease rather than the growth or survival of the bacterium itself offer a tantalizing prospect of novel antimicrobials. They may also reduce the propensity to induce resistance by removing the strong selection pressure imparted by bactericidal or bacteriostatic agents. In the human pathogen Pseudomonas aeruginosa, disulfide bond protein A (PaDsbA1) plays a central role in the oxidative folding of virulence factors and is therefore an attractive target for the development of new anti-virulence antimicrobials. Using a fragment-based approach we have identified small molecules that bind to PaDsbA1. The fragment hits show selective binding to PaDsbA1 over the DsbA protein from Escherichia coli, suggesting that developing species-specific narrow-spectrum inhibitors of DsbA enzymes may be feasible. Structures of a co-complex of PaDsbA1 with the highest affinity fragment identified in the screen reveal that the fragment binds on the non-catalytic surface of the protein at a domain interface. This biophysical and structural data represent a starting point in the development of higher affinity compounds, which will be assessed for their potential as selective PaDsbA1 inhibitors. PMID:28346540

  20. Population Demographic History Can Cause the Appearance of Recombination Hotspots

    Science.gov (United States)

    Johnston, Henry R.; Cutler, David J.

    2012-01-01

    Although the prevailing view among geneticists suggests that recombination hotspots exist ubiquitously across the human genome, there is only limited experimental evidence from a few genomic regions to support the generality of this claim. A small number of true recombination hotspots are well supported experimentally, but the vast majority of hotspots have been identified on the basis of population genetic inferences from the patterns of linkage disequilibrium (LD) seen in the human population. These inferences are made assuming a particular model of human history, and one of the assumptions of that model is that the effective population size of humans has remained constant throughout our history. Our results show that relaxation of the constant population size assumption can create LD and variation patterns that are qualitatively and quantitatively similar to human populations without any need to invoke localized hotspots of recombination. In other words, apparent recombination hotspots could be an artifact of variable population size over time. Several lines of evidence suggest that the vast majority of hotspots identified on the basis of LD information are unlikely to have elevated recombination rates. PMID:22560089

  1. VT Biodiversity Project - Biological Hotspots

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) This dataset is the result of an effort to map biological "hotspots" in Vermont based on the "element occurrences" in the Nongame and Natural...

  2. MODIS Hotspot Validation over Thailand

    Directory of Open Access Journals (Sweden)

    Veerachai Tanpipat

    2009-11-01

    Full Text Available To ensure remote sensing MODIS hotspot (also known as active fire products or hotspots quality and precision in forest fire control and management in Thailand, an increased level of confidence is needed. Accuracy assessment of MODIS hotspots utilizing field survey data validation is described. A quantitative evaluation of MODIS hotspot products has been carried out since the 2007 forest fire season. The carefully chosen hotspots were scattered throughout the country and within the protected areas of the National Parks and Wildlife Sanctuaries. Three areas were selected as test sites for validation guidelines. Both ground and aerial field surveys were also conducted in this study by the Forest Fire Control Division, National Park, Wildlife and Plant Conversation Department, Ministry of Natural Resources and Environment, Thailand. High accuracy of 91.84 %, 95.60% and 97.53% for the 2007, 2008 and 2009 fire seasons were observed, resulting in increased confidence in the use of MODIS hotspots for forest fire control and management in Thailand.

  3. Genome-wide screens for in vivo Tinman binding sites identify cardiac enhancers with diverse functional architectures.

    Directory of Open Access Journals (Sweden)

    Hong Jin

    Full Text Available The NK homeodomain factor Tinman is a crucial regulator of early mesoderm patterning and, together with the GATA factor Pannier and the Dorsocross T-box factors, serves as one of the key cardiogenic factors during specification and differentiation of heart cells. Although the basic framework of regulatory interactions driving heart development has been worked out, only about a dozen genes involved in heart development have been designated as direct Tinman target genes to date, and detailed information about the functional architectures of their cardiac enhancers is lacking. We have used immunoprecipitation of chromatin (ChIP from embryos at two different stages of early cardiogenesis to obtain a global overview of the sequences bound by Tinman in vivo and their linked genes. Our data from the analysis of ~50 sequences with high Tinman occupancy show that the majority of such sequences act as enhancers in various mesodermal tissues in which Tinman is active. All of the dorsal mesodermal and cardiac enhancers, but not some of the others, require tinman function. The cardiac enhancers feature diverse arrangements of binding motifs for Tinman, Pannier, and Dorsocross. By employing these cardiac and non-cardiac enhancers in machine learning approaches, we identify a novel motif, termed CEE, as a classifier for cardiac enhancers. In vivo assays for the requirement of the binding motifs of Tinman, Pannier, and Dorsocross, as well as the CEE motifs in a set of cardiac enhancers, show that the Tinman sites are essential in all but one of the tested enhancers; although on occasion they can be functionally redundant with Dorsocross sites. The enhancers differ widely with respect to their requirement for Pannier, Dorsocross, and CEE sites, which we ascribe to their different position in the regulatory circuitry, their distinct temporal and spatial activities during cardiogenesis, and functional redundancies among different factor binding sites.

  4. The history, hotspots, and trends of electrocardiogram.

    Science.gov (United States)

    Yang, Xiang-Lin; Liu, Guo-Zhen; Tong, Yun-Hai; Yan, Hong; Xu, Zhi; Chen, Qi; Liu, Xiang; Zhang, Hong-Hao; Wang, Hong-Bo; Tan, Shao-Hua

    2015-07-01

    The electrocardiogram (ECG) has broad applications in clinical diagnosis and prognosis of cardiovascular disease. Many researchers have contributed to its progressive development. To commemorate those pioneers, and to better study and promote the use of ECG, we reviewed and present here a systematic introduction about the history, hotspots, and trends of ECG. In the historical part, information including the invention, improvement, and extensive applications of ECG, such as in long QT syndrome (LQTS), angina, and myocardial infarction (MI), are chronologically presented. New technologies and applications from the 1990s are also introduced. In the second part, we use the bibliometric analysis method to analyze the hotspots in the field of ECG-related research. By using total citations and year-specific total citations as our main criteria, four key hotspots in ECG-related research were identified from 11 articles, including atrial fibrillation, LQTS, angina and MI, and heart rate variability. Recent studies in those four areas are also reported. In the final part, we discuss the future trends concerning ECG-related research. The authors believe that improvement of the ECG instrumentation, big data mining for ECG, and the accuracy of diagnosis and application will be areas of continuous concern.

  5. Using ecological niche modeling to determine avian richness hotspots

    Directory of Open Access Journals (Sweden)

    R. Mirzaei

    2017-04-01

    Full Text Available Understanding distributions of wildlife species is a key step towards identifying biodiversity hotspots and designing effective conservation strategies. In this paper, the spatial pattern of diversity of birds in Golestan Province, Iran was estimated. Ecological niche modeling was used to determine distributions of 144 bird species across the province using a maximum entropy algorithm. Richness maps across all birds, and separately for rare and threatened species, were prepared as approximations to hotspots. Results showed close similarity between hotspots for all birds and those for rare birds; hotspots were concentrated in the southern and especially the southwestern parts of the province. Hotspots for threatened birds tended more to the central and especially the western parts of the province, which include coastal habitats. Based on three criteria, it is clear that the western part is the most important area of the province in terms of bird Faunas. Despite some shortcomings, hotspot analysis for birds could be applied to guide conservation efforts and provide useful tool towards efficient conservation action.

  6. Pollination decays in biodiversity hotspots.

    Science.gov (United States)

    Vamosi, Jana C; Knight, Tiffany M; Steets, Janette A; Mazer, Susan J; Burd, Martin; Ashman, Tia-Lynn

    2006-01-24

    As pollinators decline globally, competition for their services is expected to intensify, and this antagonism may be most severe where the number of plant species is the greatest. Using meta-analysis and comparative phylogenetic analysis, we provide a global-scale test of whether reproduction becomes more limited by pollen receipt (pollen limitation) as the number of coexisting plant species increases. As predicted, we find a significant positive relationship between pollen limitation and species richness. In addition, this pattern is particularly strong for species that are obligately outcrossing and for trees relative to herbs or shrubs. We suggest that plants occurring in species-rich communities may be more prone to pollen limitation because of interspecific competition for pollinators. As a consequence, plants in biodiversity hotspots may have a higher risk of extinction and/or experience increased selection pressure to specialize on certain pollinators or diversify into different phenological niches. The combination of higher pollen limitation and habitat destruction represents a dual risk to tropical plant species that has not been previously identified.

  7. Use of a Phage-Display Method to Identify Peptides that Bind to a Tin Oxide Nanosheets.

    Science.gov (United States)

    Nakazawa, Hikaru; Seta, Yasuko; Hirose, Tatsuya; Masuda, Yoshitake; Umetsu, Mitsuo

    2018-01-01

    Nanosheets of SnO2 which an n-type semiconductor with a rutile-type crystalline structure are predominantly used as gas sensors. SnO2 nanosheets have a tetragonal crystal structure where growth along the c-axis is suppressed to form a sheet. The major exposed facets of SnO2 nanosheets have {110}, {101} and {211} crystal planes along the a-axis, with the reduced {110} surface having a particularly high surface energy. Identifying peptides that bind to specific crystal planes by using peptide phage-display approach will increase the potential applications of metal oxide nanomaterials by fusing proteins with desirable active sites to peptides that adsorb at high density on the major exposed crystal plane of nanosheets. It may be possible to construct highly sensitive biosensors. The main objective of the present study is to identify peptides that adsorb preferentially to a SnO2 nanosheet by using peptide-phage display approach. Four milligrams of SnO2 nanosheet were mixed with 1011 plaque-forming units of Ph.D.-12 Phage Display Peptide Library. Phage-bound nanosheet particles were washed 10 times with 1 mL of phosphatebuffered saline containing 0.5% Tween 20. Phages bound to the nanosheet were eluted with three different buffers: (1) high-salt buffer containing 2 M NaCl (pH 7.5); (2) acidic buffer containing 200 mM Gly-HCl (pH 2.2); and (3) high-phosphate-ion buffer containing 500 mM NaH2PO4 (pH 7.5). The eluted phages were subjected to four or five rounds of biopanning. At each round, individual plaques were picked from the plates, and the amino acid sequences of the peptides were identified by DNA sequencing. The identified SnO2-binding peptides labeled with fluorescein isothiocyanate were synthesized. Adsorption isotherms were constructed at peptide concentrations ranging from 0.25 to 2.0 µM with 4mg of nanomaterials. We were determined the sequences of 11 clones with the high-salt buffer, 7 with the high-phosphateion buffers, and 6 with the acidic buffer and

  8. Microbial micropatches within microbial hotspots

    Science.gov (United States)

    Smith, Renee J.; Tobe, Shanan S.; Paterson, James S.; Seymour, Justin R.; Oliver, Rod L.; Mitchell, James G.

    2018-01-01

    The spatial distributions of organism abundance and diversity are often heterogeneous. This includes the sub-centimetre distributions of microbes, which have ‘hotspots’ of high abundance, and ‘coldspots’ of low abundance. Previously we showed that 300 μl abundance hotspots, coldspots and background regions were distinct at all taxonomic levels. Here we build on these results by showing taxonomic micropatches within these 300 μl microscale hotspots, coldspots and background regions at the 1 μl scale. This heterogeneity among 1 μl subsamples was driven by heightened abundance of specific genera. The micropatches were most pronounced within hotspots. Micropatches were dominated by Pseudomonas, Bacteroides, Parasporobacterium and Lachnospiraceae incertae sedis, with Pseudomonas and Bacteroides being responsible for a shift in the most dominant genera in individual hotspot subsamples, representing up to 80.6% and 47.3% average abundance, respectively. The presence of these micropatches implies the ability these groups have to create, establish themselves in, or exploit heterogeneous microenvironments. These genera are often particle-associated, from which we infer that these micropatches are evidence for sub-millimetre aggregates and the aquatic polymer matrix. These findings support the emerging paradigm that the microscale distributions of planktonic microbes are numerically and taxonomically heterogeneous at scales of millimetres and less. We show that microscale microbial hotspots have internal structure within which specific local nutrient exchanges and cellular interactions might occur. PMID:29787564

  9. Distribution, congruence, and hotspots of higher plants in China.

    Science.gov (United States)

    Zhao, Lina; Li, Jinya; Liu, Huiyuan; Qin, Haining

    2016-01-11

    Identifying biodiversity hotspots has become a central issue in setting up priority protection areas, especially as financial resources for biological diversity conservation are limited. Taking China's Higher Plants Red List (CHPRL), including Bryophytes, Ferns, Gymnosperms, Angiosperms, as the data source, we analyzed the geographic patterns of species richness, endemism, and endangerment via data processing at a fine grid-scale with an average edge length of 30 km based on three aspects of richness information: species richness, endemic species richness, and threatened species richness. We sought to test the accuracy of hotspots used in identifying conservation priorities with regard to higher plants. Next, we tested the congruence of the three aspects and made a comparison of the similarities and differences between the hotspots described in this paper and those in previous studies. We found that over 90% of threatened species in China are concentrated. While a high spatial congruence is observed among the three measures, there is a low congruence between two different sets of hotspots. Our results suggest that biodiversity information should be considered when identifying biological hotspots. Other factors, such as scales, should be included as well to develop biodiversity conservation plans in accordance with the region's specific conditions.

  10. Sampling effects on the identification of roadkill hotspots: Implications for survey design.

    Science.gov (United States)

    Santos, Sara M; Marques, J Tiago; Lourenço, André; Medinas, Denis; Barbosa, A Márcia; Beja, Pedro; Mira, António

    2015-10-01

    Although locating wildlife roadkill hotspots is essential to mitigate road impacts, the influence of study design on hotspot identification remains uncertain. We evaluated how sampling frequency affects the accuracy of hotspot identification, using a dataset of vertebrate roadkills (n = 4427) recorded over a year of daily surveys along 37 km of roads. "True" hotspots were identified using this baseline dataset, as the 500-m segments where the number of road-killed vertebrates exceeded the upper 95% confidence limit of the mean, assuming a Poisson distribution of road-kills per segment. "Estimated" hotspots were identified likewise, using datasets representing progressively lower sampling frequencies, which were produced by extracting data from the baseline dataset at appropriate time intervals (1-30 days). Overall, 24.3% of segments were "true" hotspots, concentrating 40.4% of roadkills. For different groups, "true" hotspots accounted from 6.8% (bats) to 29.7% (small birds) of road segments, concentrating from 60% (lizards, lagomorphs, carnivores) of roadkills. Spatial congruence between "true" and "estimated" hotspots declined rapidly with increasing time interval between surveys, due primarily to increasing false negatives (i.e., missing "true" hotspots). There were also false positives (i.e., wrong "estimated" hotspots), particularly at low sampling frequencies. Spatial accuracy decay with increasing time interval between surveys was higher for smaller-bodied (amphibians, reptiles, small birds, small mammals) than for larger-bodied species (birds of prey, hedgehogs, lagomorphs, carnivores). Results suggest that widely used surveys at weekly or longer intervals may produce poor estimates of roadkill hotspots, particularly for small-bodied species. Surveying daily or at two-day intervals may be required to achieve high accuracy in hotspot identification for multiple species. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. The spatial regulation of meiotic recombination hotspots: are all DSB hotspots crossover hotspots?

    Science.gov (United States)

    Serrentino, Maria-Elisabetta; Borde, Valérie

    2012-07-15

    A key step for the success of meiosis is programmed homologous recombination, during which crossovers, or exchange of chromosome arms, take place. Crossovers increase genetic diversity but their main function is to ensure accurate chromosome segregation. Defects in crossover number and position produce aneuploidies that represent the main cause of miscarriages and chromosomal abnormalities such as Down's syndrome. Recombination is initiated by the formation of programmed double strand breaks (DSBs), which occur preferentially at places called DSB hotspots. Among all DSBs generated, only a small fraction is repaired by crossover, the other being repaired by other homologous recombination pathways. Crossover maps have been generated in a number of organisms, defining crossover hotspots. With the availability of genome-wide maps of DSBs as well as the ability to measure genetically the repair outcome at several hotspots, it is becoming more and more clear that not all DSB hotspots behave the same for crossover formation, suggesting that chromosomal features distinguish different types of hotspots. Copyright © 2012. Published by Elsevier Inc.

  12. A Sequence in the loop domain of hepatitis C virus E2 protein identified in silico as crucial for the selective binding to human CD81.

    Directory of Open Access Journals (Sweden)

    Chun-Chun Chang

    Full Text Available Hepatitis C virus (HCV is a species-specific pathogenic virus that infects only humans and chimpanzees. Previous studies have indicated that interactions between the HCV E2 protein and CD81 on host cells are required for HCV infection. To determine the crucial factors for species-specific interactions at the molecular level, this study employed in silico molecular docking involving molecular dynamic simulations of the binding of HCV E2 onto human and rat CD81s. In vitro experiments including surface plasmon resonance measurements and cellular binding assays were applied for simple validations of the in silico results. The in silico studies identified two binding regions on the HCV E2 loop domain, namely E2-site1 and E2-site2, as being crucial for the interactions with CD81s, with the E2-site2 as the determinant factor for human-specific binding. Free energy calculations indicated that the E2/CD81 binding process might follow a two-step model involving (i the electrostatic interaction-driven initial binding of human-specific E2-site2, followed by (ii changes in the E2 orientation to facilitate the hydrophobic and van der Waals interaction-driven binding of E2-site1. The sequence of the human-specific, stronger-binding E2-site2 could serve as a candidate template for the future development of HCV-inhibiting peptide drugs.

  13. Proteomic analysis identifies insulin-like growth factor-binding protein-related protein-1 as a podocyte product.

    Science.gov (United States)

    Matsumoto, Takayuki; Hess, Sonja; Kajiyama, Hiroshi; Sakairi, Toru; Saleem, Moin A; Mathieson, Peter W; Nojima, Yoshihisa; Kopp, Jeffrey B

    2010-10-01

    The podocyte secretory proteome may influence the phenotype of adjacent podocytes, endothelial cells, parietal epithelial cells, and tubular epithelial cells but has not been systematically characterized. We have initiated studies to characterize this proteome, with the goal of further understanding the podocyte cell biology. We cultured differentiated conditionally immortalized human podocytes and subjected the proteins in conditioned medium to mass spectrometry. At a false discovery rate of factor-binding protein-related protein-1 (IGFBP-rP1), was expressed in mRNA and protein of cultured podocytes. In addition, transforming growth factor-β1 stimulation increased IGFBP-rP1 in conditioned medium. We analyzed IGFBP-rP1 glomerular expression in a mouse model of human immunodeficiency virus-associated nephropathy. IGFBP-rP1 was absent from podocytes of normal mice and was expressed in podocytes and pseudocrescents of transgenic mice, where it was coexpressed with desmin, a podocyte injury marker. We conclude that IGFBP-rP1 may be a product of injured podocytes. Further analysis of the podocyte secretory proteome may identify biomarkers of podocyte injury.

  14. Hopping hotspots: global shifts in marine biodiversity.

    Science.gov (United States)

    Renema, W; Bellwood, D R; Braga, J C; Bromfield, K; Hall, R; Johnson, K G; Lunt, P; Meyer, C P; McMonagle, L B; Morley, R J; O'Dea, A; Todd, J A; Wesselingh, F P; Wilson, M E J; Pandolfi, J M

    2008-08-01

    Hotspots of high species diversity are a prominent feature of modern global biodiversity patterns. Fossil and molecular evidence is starting to reveal the history of these hotspots. There have been at least three marine biodiversity hotspots during the past 50 million years. They have moved across almost half the globe, with their timing and locations coinciding with major tectonic events. The birth and death of successive hotspots highlights the link between environmental change and biodiversity patterns. The antiquity of the taxa in the modern Indo-Australian Archipelago hotspot emphasizes the role of pre-Pleistocene events in shaping modern diversity patterns.

  15. Geographic Hotspots of Critical National Infrastructure.

    Science.gov (United States)

    Thacker, Scott; Barr, Stuart; Pant, Raghav; Hall, Jim W; Alderson, David

    2017-12-01

    Failure of critical national infrastructures can result in major disruptions to society and the economy. Understanding the criticality of individual assets and the geographic areas in which they are located is essential for targeting investments to reduce risks and enhance system resilience. Within this study we provide new insights into the criticality of real-life critical infrastructure networks by integrating high-resolution data on infrastructure location, connectivity, interdependence, and usage. We propose a metric of infrastructure criticality in terms of the number of users who may be directly or indirectly disrupted by the failure of physically interdependent infrastructures. Kernel density estimation is used to integrate spatially discrete criticality values associated with individual infrastructure assets, producing a continuous surface from which statistically significant infrastructure criticality hotspots are identified. We develop a comprehensive and unique national-scale demonstration for England and Wales that utilizes previously unavailable data from the energy, transport, water, waste, and digital communications sectors. The testing of 200,000 failure scenarios identifies that hotspots are typically located around the periphery of urban areas where there are large facilities upon which many users depend or where several critical infrastructures are concentrated in one location. © 2017 Society for Risk Analysis.

  16. Applying Hotspot Detection Methods in Forestry: A Case Study of Chestnut Oak Regeneration

    International Nuclear Information System (INIS)

    Fei, S.

    2010-01-01

    Hotspot detection has been widely adopted in health sciences for disease surveillance, but rarely in natural resource disciplines. In this paper, two spatial scan statistics (SaT Scan and Cluster Seer) and a non spatial classification and regression trees method were evaluated as techniques for identifying chestnut oak (Quercus Montana) regeneration hotspots among 50 mixed-oak stands in the central Appalachian region of the eastern United States. Hotspots defined by the three methods had a moderate level of conformity and revealed similar chestnut oak regeneration site affinity. Chestnut oak regeneration hotspots were positively associated with the abundance of chestnut oak trees in the over story and a moderate cover of heather species (Vaccinium and Gaylussacia spp.) but were negatively associated with the abundance of hay scented fern (Dennstaedtia punctilobula) and mountain laurel (Kalmia latiforia). In general, hotspot detection is a viable tool for assisting natural resource managers with identifying areas possessing significantly high or low tree regeneration.

  17. Applying Hotspot Detection Methods in Forestry: A Case Study of Chestnut Oak Regeneration

    Directory of Open Access Journals (Sweden)

    Songlin Fei

    2010-01-01

    Full Text Available Hotspot detection has been widely adopted in health sciences for disease surveillance, but rarely in natural resource disciplines. In this paper, two spatial scan statistics (SaTScan and ClusterSeer and a nonspatial classification and regression trees method were evaluated as techniques for identifying chestnut oak (Quercus Montana regeneration hotspots among 50 mixed-oak stands in the central Appalachian region of the eastern United States. Hotspots defined by the three methods had a moderate level of conformity and revealed similar chestnut oak regeneration site affinity. Chestnut oak regeneration hotspots were positively associated with the abundance of chestnut oak trees in the overstory and a moderate cover of heather species (Vaccinium and Gaylussacia spp. but were negatively associated with the abundance of hayscented fern (Dennstaedtia punctilobula and mountain laurel (Kalmia latiforia. In general, hotspot detection is a viable tool for assisting natural resource managers with identifying areas possessing significantly high or low tree regeneration.

  18. Efficient Assessment of Social Hotspots in the Supply Chains of 100 Product Categories Using the Social Hotspots Database

    Directory of Open Access Journals (Sweden)

    Catherine Benoît Norris

    2014-10-01

    Full Text Available Data collection, or the inventory step, is often the most labor-intensive phase of any Life Cycle Assessment (LCA study. The S-LCA Guidelines and numerous authors have recommended generic assessment in this first phase of an S-LCA. In an effort to identify the social hotspots in the supply chains of 100 product categories during just a few months’ time, adopting a streamlined approach was essential. The Social Hotspots Database system was developed by New Earth over 5 years. It includes a Global Input Output (IO model derived from the Global Trade Analysis Project, a Worker Hours Model constructed using annual wage payments and wage rates by country and sector, and Social Theme Tables covering 22 themes within five Social Impact Categories—Labor Rights and Decent Work, Health and Safety, Human Rights, Governance and Community Impacts. The data tables identify social risks for over 100 indicators. Both the ranking of worker hour intensity and the risk levels across multiple social themes for the Country Specific Sectors (CSS within a product category supply chain are used to calculate Social Hotspots Indexes (SHI using an additive weighting method. The CSS with the highest SHI are highlighted as social hotspots within the supply chain of the product in question. This system was tested in seven case studies in 2011. In order to further limit the number of hotspots, a set of prioritization rules was applied. This paper will review the method implemented to study the social hotspots of the 100 product categories and provide one detailed example. Limitations of the approach and recommended research avenues will be outlined.

  19. A Glance at Recombination Hotspots in the Domestic Cat.

    Directory of Open Access Journals (Sweden)

    Hasan Alhaddad

    Full Text Available Recombination has essential roles in increasing genetic variability within a population and in ensuring successful meiotic events. The objective of this study is to (i infer the population-scaled recombination rate (ρ, and (ii identify and characterize regions of increased recombination rate for the domestic cat, Felis silvestris catus. SNPs (n = 701 were genotyped in twenty-two East Asian feral cats (random bred. The SNPs covered ten different chromosomal regions (A1, A2, B3, C2, D1, D2, D4, E2, F2, X with an average region size of 850 Kb and an average SNP density of 70 SNPs/region. The Bayesian method in the program inferRho was used to infer regional population recombination rates and hotspots localities. The regions exhibited variable population recombination rates and four decisive recombination hotspots were identified on cat chromosome A2, D1, and E2 regions. As a description of the identified hotspots, no correlation was detected between the GC content and the locality of recombination spots, and the hotspots enclosed L2 LINE elements and MIR and tRNA-Lys SINE elements.

  20. Crystal structure of the gamma-2 herpesvirus LANA DNA binding domain identifies charged surface residues which impact viral latency.

    Directory of Open Access Journals (Sweden)

    Bruno Correia

    Full Text Available Latency-associated nuclear antigen (LANA mediates γ2-herpesvirus genome persistence and regulates transcription. We describe the crystal structure of the murine gammaherpesvirus-68 LANA C-terminal domain at 2.2 Å resolution. The structure reveals an alpha-beta fold that assembles as a dimer, reminiscent of Epstein-Barr virus EBNA1. A predicted DNA binding surface is present and opposite this interface is a positive electrostatic patch. Targeted DNA recognition substitutions eliminated DNA binding, while certain charged patch mutations reduced bromodomain protein, BRD4, binding. Virus containing LANA abolished for DNA binding was incapable of viable latent infection in mice. Virus with mutations at the charged patch periphery exhibited substantial deficiency in expansion of latent infection, while central region substitutions had little effect. This deficiency was independent of BRD4. These results elucidate the LANA DNA binding domain structure and reveal a unique charged region that exerts a critical role in viral latent infection, likely acting through a host cell protein(s.

  1. A Novel Approach for Identification and Ranking of Road Traffic Accident Hotspots

    Directory of Open Access Journals (Sweden)

    Zahran El-Said M.M.

    2017-01-01

    Full Text Available Road Traffic Accidents (RTA are known to be one of the main causes of fatalities worldwide. One usef ul approach to improve road safety is through the identification of RT A hotspots along a road, so they can be prioritised and treated. This paper introduces an approach based on Geographical Information System (GI S to identify and prioritise RTA hotspots along a road network using historical RTA data. One particular urban road in Brunei with a historically high rate of RT As, Jalan Gadong, was selected as a case study. Five years of historical RTA data were acquired from the relevant authorities and input into a GIS database. GI S analysis was then used to identify the spatial extension of the RT A hotspots. The RT A hotspots were ranked according to three different schemes: frequency, severity and socio-economic impact of RTAs. A composite ranking scheme was also developed to combine these schemes; this enabled the prioritisation and development of intervention and maintenance programmes of the identified RTA hotspots. A visualisation method of the RTA spatial distribution within each identified RTA hotspot was also developed to determine the most risky road stretches within each hotspot, which is important for treatment prioritisation when limited resources are available.

  2. Effects of six APOA5 variants, identified in patients with severe hypertriglyceridemia, on in vitro lipoprotein lipase activity and receptor binding

    NARCIS (Netherlands)

    Dorfmeister, B.; Zeng, W. W.; Dichlberger, A.; Nilsson, S. K.; Schaap, F. G.; Hubacek, J. A.; Merkel, M.; Cooper, J. A.; Lookene, A.; Putt, W.; Whittall, R.; Lee, P. J.; Lins, L.; Delsaux, N.; Nierman, M.; Kuivenhoven, J. A.; Kastelein, J. J. P.; Vrablik, M.; Olivecrona, G.; Schneider, W. J.; Heeren, J.; Humphries, S. E.; Talmud, P. J.

    2008-01-01

    OBJECTIVE: The purpose of this study was to identify rare APOA5 variants in 130 severe hypertriglyceridemic patients by sequencing, and to test their functionality, since no patient recall was possible. METHODS AND RESULTS: We studied the impact in vitro on LPL activity and receptor binding of 3

  3. Combining modelling and mutagenesis studies of synaptic vesicle protein 2A to identify a series of residues involved in racetam binding.

    Science.gov (United States)

    Shi, Jiye; Anderson, Dina; Lynch, Berkley A; Castaigne, Jean-Gabriel; Foerch, Patrik; Lebon, Florence

    2011-10-01

    LEV (levetiracetam), an antiepileptic drug which possesses a unique profile in animal models of seizure and epilepsy, has as its unique binding site in brain, SV2A (synaptic vesicle protein 2A). Previous studies have used a chimaeric and site-specific mutagenesis approach to identify three residues in the putative tenth transmembrane helix of SV2A that, when mutated, alter binding of LEV and related racetam derivatives to SV2A. In the present paper, we report a combined modelling and mutagenesis study that successfully identifies another 11 residues in SV2A that appear to be involved in ligand binding. Sequence analysis and modelling of SV2A suggested residues equivalent to critical functional residues of other MFS (major facilitator superfamily) transporters. Alanine scanning of these and other SV2A residues resulted in the identification of residues affecting racetam binding, including Ile273 which differentiated between racetam analogues, when mutated to alanine. Integrating mutagenesis results with docking analysis led to the construction of a mutant in which six SV2A residues were replaced with corresponding SV2B residues. This mutant showed racetam ligand-binding affinity intermediate to the affinities observed for SV2A and SV2B.

  4. New Tests of the Fixed Hotspot Approximation

    Science.gov (United States)

    Gordon, R. G.; Andrews, D. L.; Horner-Johnson, B. C.; Kumar, R. R.

    2005-05-01

    We present new methods for estimating uncertainties in plate reconstructions relative to the hotspots and new tests of the fixed hotspot approximation. We find no significant motion between Pacific hotspots, on the one hand, and Indo-Atlantic hotspots, on the other, for the past ~ 50 Myr, but large and significant apparent motion before 50 Ma. Whether this motion is truly due to motion between hotspots or alternatively due to flaws in the global plate motion circuit can be tested with paleomagnetic data. These tests give results consistent with the fixed hotspot approximation and indicate significant misfits when a relative plate motion circuit through Antarctica is employed for times before 50 Ma. If all of the misfit to the global plate motion circuit is due to motion between East and West Antarctica, then that motion is 800 ± 500 km near the Ross Sea Embayment and progressively less along the Trans-Antarctic Mountains toward the Weddell Sea. Further paleomagnetic tests of the fixed hotspot approximation can be made. Cenozoic and Cretaceous paleomagnetic data from the Pacific plate, along with reconstructions of the Pacific plate relative to the hotspots, can be used to estimate an apparent polar wander (APW) path of Pacific hotspots. An APW path of Indo-Atlantic hotspots can be similarly estimated (e.g. Besse & Courtillot 2002). If both paths diverge in similar ways from the north pole of the hotspot reference frame, it would indicate that the hotspots have moved in unison relative to the spin axis, which may be attributed to true polar wander. If the two paths diverge from one another, motion between Pacific hotspots and Indo-Atlantic hotspots would be indicated. The general agreement of the two paths shows that the former is more important than the latter. The data require little or no motion between groups of hotspots, but up to ~10 mm/yr of motion is allowed within uncertainties. The results disagree, in particular, with the recent extreme interpretation of

  5. Predicting and analyzing DNA-binding domains using a systematic approach to identifying a set of informative physicochemical and biochemical properties

    Science.gov (United States)

    2011-01-01

    Background Existing methods of predicting DNA-binding proteins used valuable features of physicochemical properties to design support vector machine (SVM) based classifiers. Generally, selection of physicochemical properties and determination of their corresponding feature vectors rely mainly on known properties of binding mechanism and experience of designers. However, there exists a troublesome problem for designers that some different physicochemical properties have similar vectors of representing 20 amino acids and some closely related physicochemical properties have dissimilar vectors. Results This study proposes a systematic approach (named Auto-IDPCPs) to automatically identify a set of physicochemical and biochemical properties in the AAindex database to design SVM-based classifiers for predicting and analyzing DNA-binding domains/proteins. Auto-IDPCPs consists of 1) clustering 531 amino acid indices in AAindex into 20 clusters using a fuzzy c-means algorithm, 2) utilizing an efficient genetic algorithm based optimization method IBCGA to select an informative feature set of size m to represent sequences, and 3) analyzing the selected features to identify related physicochemical properties which may affect the binding mechanism of DNA-binding domains/proteins. The proposed Auto-IDPCPs identified m=22 features of properties belonging to five clusters for predicting DNA-binding domains with a five-fold cross-validation accuracy of 87.12%, which is promising compared with the accuracy of 86.62% of the existing method PSSM-400. For predicting DNA-binding sequences, the accuracy of 75.50% was obtained using m=28 features, where PSSM-400 has an accuracy of 74.22%. Auto-IDPCPs and PSSM-400 have accuracies of 80.73% and 82.81%, respectively, applied to an independent test data set of DNA-binding domains. Some typical physicochemical properties discovered are hydrophobicity, secondary structure, charge, solvent accessibility, polarity, flexibility, normalized Van Der

  6. High-throughput screening identifies small molecules that bind to the RAS:SOS:RAS complex and perturb RAS signaling.

    Science.gov (United States)

    Burns, Michael C; Howes, Jennifer E; Sun, Qi; Little, Andrew J; Camper, DeMarco V; Abbott, Jason R; Phan, Jason; Lee, Taekyu; Waterson, Alex G; Rossanese, Olivia W; Fesik, Stephen W

    2018-05-01

    K-RAS is mutated in approximately 30% of human cancers, resulting in increased RAS signaling and tumor growth. Thus, RAS is a highly validated therapeutic target, especially in tumors of the pancreas, lung and colon. Although directly targeting RAS has proven to be challenging, it may be possible to target other proteins involved in RAS signaling, such as the guanine nucleotide exchange factor Son of Sevenless (SOS). We have previously reported on the discovery of small molecules that bind to SOS1, activate SOS-mediated nucleotide exchange on RAS, and paradoxically inhibit ERK phosphorylation (Burns et al., PNAS, 2014). Here, we describe the discovery of additional, structurally diverse small molecules that also bind to SOS1 in the same pocket and elicit similar biological effects. We tested >160,000 compounds in a fluorescence-based assay to assess their effects on SOS-mediated nucleotide exchange. X-Ray structures revealed that these small molecules bind to the CDC25 domain of SOS1. Compounds that elicited high levels of nucleotide exchange activity in vitro increased RAS-GTP levels in cells, and inhibited phospho ERK levels at higher treatment concentrations. The identification of structurally diverse SOS1 binding ligands may assist in the discovery of new molecules designed to target RAS-driven tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. A strategy for interaction site prediction between phospho-binding modules and their partners identified from proteomic data.

    Science.gov (United States)

    Aucher, Willy; Becker, Emmanuelle; Ma, Emilie; Miron, Simona; Martel, Arnaud; Ochsenbein, Françoise; Marsolier-Kergoat, Marie-Claude; Guerois, Raphaël

    2010-12-01

    Small and large scale proteomic technologies are providing a wealth of potential interactions between proteins bearing phospho-recognition modules and their substrates. Resulting interaction maps reveal such a dense network of interactions that the functional dissection and understanding of these networks often require to break specific interactions while keeping the rest intact. Here, we developed a computational strategy, called STRIP, to predict the precise interaction site involved in an interaction with a phospho-recognition module. The method was validated by a two-hybrid screen carried out using the ForkHead Associated (FHA)1 domain of Rad53, a key protein of Saccharomyces cerevisiae DNA checkpoint, as a bait. In this screen we detected 11 partners, including Cdc7 and Cdc45, essential components of the DNA replication machinery. FHA domains are phospho-threonine binding modules and the threonines involved in both interactions could be predicted using the STRIP strategy. The threonines T484 and T189 in Cdc7 and Cdc45, respectively, were mutated and loss of binding could be monitored experimentally with the full-length proteins. The method was further tested for the analysis of 63 known Rad53 binding partners and provided several key insights regarding the threonines likely involved in these interactions. The STRIP method relies on a combination of conservation, phosphorylation likelihood, and binding specificity criteria and can be accessed via a web interface at http://biodev.extra.cea.fr/strip/.

  8. A Strategy for Interaction Site Prediction between Phospho-binding Modules and their Partners Identified from Proteomic Data*

    Science.gov (United States)

    Aucher, Willy; Becker, Emmanuelle; Ma, Emilie; Miron, Simona; Martel, Arnaud; Ochsenbein, Françoise; Marsolier-Kergoat, Marie-Claude; Guerois, Raphaël

    2010-01-01

    Small and large scale proteomic technologies are providing a wealth of potential interactions between proteins bearing phospho-recognition modules and their substrates. Resulting interaction maps reveal such a dense network of interactions that the functional dissection and understanding of these networks often require to break specific interactions while keeping the rest intact. Here, we developed a computational strategy, called STRIP, to predict the precise interaction site involved in an interaction with a phospho-recognition module. The method was validated by a two-hybrid screen carried out using the ForkHead Associated (FHA)1 domain of Rad53, a key protein of Saccharomyces cerevisiae DNA checkpoint, as a bait. In this screen we detected 11 partners, including Cdc7 and Cdc45, essential components of the DNA replication machinery. FHA domains are phospho-threonine binding modules and the threonines involved in both interactions could be predicted using the STRIP strategy. The threonines T484 and T189 in Cdc7 and Cdc45, respectively, were mutated and loss of binding could be monitored experimentally with the full-length proteins. The method was further tested for the analysis of 63 known Rad53 binding partners and provided several key insights regarding the threonines likely involved in these interactions. The STRIP method relies on a combination of conservation, phosphorylation likelihood, and binding specificity criteria and can be accessed via a web interface at http://biodev.extra.cea.fr/strip/. PMID:20733106

  9. Shared peptide binding of HLA Class I and II alleles associate with cutaneous nevirapine hypersensitivity and identify novel risk alleles

    DEFF Research Database (Denmark)

    Pavlos, Rebecca; McKinnon, Elizabeth J.; Ostrov, David A.

    2017-01-01

    Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation of immune responses, and the way drugs interact with the HLA peptide binding groove is important in the immunopathogenesis of T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP), is...

  10. Purification and subunit structure of a putative K sup + -channel protein identified by its binding properties for dendrotoxin I

    Energy Technology Data Exchange (ETDEWEB)

    Rehm, H.; Lazdunski, M. (Centre National de la Recherche Scientifique, Nice (France))

    1988-07-01

    The binding protein for the K{sup +}-channel toxin dendrotoxin I was purified from a detergent extract of rat brain membranes. The purification procedure utilized chromatography on DEAE-Trisacryl, affinity chromatography on a dendrotoxin-I-Aca 22 column, and wheat germ agglutinin-Affigel 10 with a final 3,800- to 4,600-fold enrichment and a recovery of 8-16%. The high affinity (K{sub d}, 40-100 pM) and specificity of the binding site are retained throughout the purification procedure. Analysis of the purified material on silver-stained NaDodSO{sub 4}/polyacrylamide gel revealed three bands of M{sub r} 76,000-80,000, 38,000 and 35,000. Interestingly, the binding site for {sup 125}I-labeled mast cell degranulating peptide, another putative K{sup +}-channel ligand from bee venom, which induces long-term potentiation in hippocampus, seems to reside on the same protein complex, as both binding sites copurify through the entire purification protocol.

  11. Purification and subunit structure of a putative K+-channel protein identified by its binding properties for dendrotoxin I

    International Nuclear Information System (INIS)

    Rehm, H.; Lazdunski, M.

    1988-01-01

    The binding protein for the K + -channel toxin dendrotoxin I was purified from a detergent extract of rat brain membranes. The purification procedure utilized chromatography on DEAE-Trisacryl, affinity chromatography on a dendrotoxin-I-Aca 22 column, and wheat germ agglutinin-Affigel 10 with a final 3,800- to 4,600-fold enrichment and a recovery of 8-16%. The high affinity (K d , 40-100 pM) and specificity of the binding site are retained throughout the purification procedure. Analysis of the purified material on silver-stained NaDodSO 4 /polyacrylamide gel revealed three bands of M r 76,000-80,000, 38,000 and 35,000. Interestingly, the binding site for 125 I-labeled mast cell degranulating peptide, another putative K + -channel ligand from bee venom, which induces long-term potentiation in hippocampus, seems to reside on the same protein complex, as both binding sites copurify through the entire purification protocol

  12. Alternative binding modes identified for growth and differentiation factor-associated serum protein (GASP) family antagonism of myostatin.

    Science.gov (United States)

    Walker, Ryan G; Angerman, Elizabeth B; Kattamuri, Chandramohan; Lee, Yun-Sil; Lee, Se-Jin; Thompson, Thomas B

    2015-03-20

    Myostatin, a member of the TGF-β family of ligands, is a strong negative regulator of muscle growth. As such, it is a prime therapeutic target for muscle wasting disorders. Similar to other TGF-β family ligands, myostatin is neutralized by binding one of a number of structurally diverse antagonists. Included are the antagonists GASP-1 and GASP-2, which are unique in that they specifically antagonize myostatin. However, little is known from a structural standpoint describing the interactions of GASP antagonists with myostatin. Here, we present the First low resolution solution structure of myostatin-free and myostatin-bound states of GASP-1 and GASP-2. Our studies have revealed GASP-1, which is 100 times more potent than GASP-2, preferentially binds myostatin in an asymmetrical 1:1 complex, whereas GASP-2 binds in a symmetrical 2:1 complex. Additionally, C-terminal truncations of GASP-1 result in less potent myostatin inhibitors that form a 2:1 complex, suggesting that the C-terminal domains of GASP-1 are the primary mediators for asymmetric complex formation. Overall, this study provides a new perspective on TGF-β antagonism, where closely related antagonists can utilize different ligand-binding strategies. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Alternative Binding Modes Identified for Growth and Differentiation Factor-associated Serum Protein (GASP) Family Antagonism of Myostatin*

    Science.gov (United States)

    Walker, Ryan G.; Angerman, Elizabeth B.; Kattamuri, Chandramohan; Lee, Yun-Sil; Lee, Se-Jin; Thompson, Thomas B.

    2015-01-01

    Myostatin, a member of the TGF-β family of ligands, is a strong negative regulator of muscle growth. As such, it is a prime therapeutic target for muscle wasting disorders. Similar to other TGF-β family ligands, myostatin is neutralized by binding one of a number of structurally diverse antagonists. Included are the antagonists GASP-1 and GASP-2, which are unique in that they specifically antagonize myostatin. However, little is known from a structural standpoint describing the interactions of GASP antagonists with myostatin. Here, we present the First low resolution solution structure of myostatin-free and myostatin-bound states of GASP-1 and GASP-2. Our studies have revealed GASP-1, which is 100 times more potent than GASP-2, preferentially binds myostatin in an asymmetrical 1:1 complex, whereas GASP-2 binds in a symmetrical 2:1 complex. Additionally, C-terminal truncations of GASP-1 result in less potent myostatin inhibitors that form a 2:1 complex, suggesting that the C-terminal domains of GASP-1 are the primary mediators for asymmetric complex formation. Overall, this study provides a new perspective on TGF-β antagonism, where closely related antagonists can utilize different ligand-binding strategies. PMID:25657005

  14. Are hotspots of evolutionary potential adequately protected in southern California?

    Science.gov (United States)

    Vandergast, A.G.; Bohonak, A.J.; Hathaway, S.A.; Boys, J.; Fisher, R.N.

    2008-01-01

    Reserves are often designed to protect rare habitats, or "typical" exemplars of ecoregions and geomorphic provinces. This approach focuses on current patterns of organismal and ecosystem-level biodiversity, but typically ignores the evolutionary processes that control the gain and loss of biodiversity at these and other levels (e.g., genetic, ecological). In order to include evolutionary processes in conservation planning efforts, their spatial components must first be identified and mapped. We describe a GIS-based approach for explicitly mapping patterns of genetic divergence and diversity for multiple species (a "multi-species genetic landscape"). Using this approach, we analyzed mitochondrial DNA datasets from 21 vertebrate and invertebrate species in southern California to identify areas with common phylogeographic breaks and high intrapopulation diversity. The result is an evolutionary framework for southern California within which patterns of genetic diversity can be analyzed in the context of historical processes, future evolutionary potential and current reserve design. Our multi-species genetic landscapes pinpoint six hotspots where interpopulation genetic divergence is consistently high, five evolutionary hotspots within which genetic connectivity is high, and three hotspots where intrapopulation genetic diversity is high. These 14 hotspots can be grouped into eight geographic areas, of which five largely are unprotected at this time. The multi-species genetic landscape approach may provide an avenue to readily incorporate measures of evolutionary process into GIS-based systematic conservation assessment and land-use planning.

  15. Detecting Recombination Hotspots from Patterns of Linkage Disequilibrium.

    Science.gov (United States)

    Wall, Jeffrey D; Stevison, Laurie S

    2016-08-09

    With recent advances in DNA sequencing technologies, it has become increasingly easy to use whole-genome sequencing of unrelated individuals to assay patterns of linkage disequilibrium (LD) across the genome. One type of analysis that is commonly performed is to estimate local recombination rates and identify recombination hotspots from patterns of LD. One method for detecting recombination hotspots, LDhot, has been used in a handful of species to further our understanding of the basic biology of recombination. For the most part, the effectiveness of this method (e.g., power and false positive rate) is unknown. In this study, we run extensive simulations to compare the effectiveness of three different implementations of LDhot. We find large differences in the power and false positive rates of these different approaches, as well as a strong sensitivity to the window size used (with smaller window sizes leading to more accurate estimation of hotspot locations). We also compared our LDhot simulation results with comparable simulation results obtained from a Bayesian maximum-likelihood approach for identifying hotspots. Surprisingly, we found that the latter computationally intensive approach had substantially lower power over the parameter values considered in our simulations. Copyright © 2016 Wall and Stevison.

  16. A starch-binding domain identified in α-amylase (AmyP) represents a new family of carbohydrate-binding modules that contribute to enzymatic hydrolysis of soluble starch.

    Science.gov (United States)

    Peng, Hui; Zheng, Yunyun; Chen, Maojiao; Wang, Ying; Xiao, Yazhong; Gao, Yi

    2014-04-02

    A novel starch-binding domain (SBD) that represents a new carbohydrate-binding module family (CBM69) was identified in the α-amylase (AmyP) of the recently established alpha-amylase subfamily GH13_37. The SBD and its homologues come mostly from marine bacteria, and phylogenetic analysis indicates that they are closely related to the CBM20 and CBM48 families. The SBD exhibited a binding preference toward raw rice starch, but the truncated mutant (AmyPΔSBD) still retained similar substrate preference. Kinetic analyses revealed that the SBD plays an important role in soluble starch hydrolysis because different catalytic efficiencies have been observed in AmyP and the AmyPΔSBD. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  17. Hotspot uranium metallogenesis in south China

    International Nuclear Information System (INIS)

    Li Ziying

    2006-01-01

    The basic concepts of mantle plume and hotspots are expounded and the hotspots are classified into continental and oceanic types. The relationship between hotspots and metallogenesis are briefly discussed, and a new theory of uranium metallogenesis related to hotspots has been put forward. The geotectonism, magmatism, sedimentation, metamorphism and metallogenesis must be closely associated with deep geodynamics of mantle plume tectonics in Meso-Cenozoic period from 220 Ma to 50 Ma in South China. The eastern part of Guidong granite massif has been proved to be a Mesozoic hotspot from aspects of geological, geophysical and geochemical evidences and its correspondent relationship to uranium metallogenesis is discussed. Finally, the uranium metallogenetic prospect has been pointed out for hydrothermal uranium mineralization in South China from the view point of hotspot uranium metallogenesis. (authors)

  18. Application of PCARES in locating the soil erosion Hotspots in the Manupali River Watershed

    OpenAIRE

    Paningbatan, E.

    2004-01-01

    In this presentation the author covers: GIS mapping of land attributes, dynamic modeling of soil erosion at watershed scale using PCARES (Predicting Catchment Runoff and Soil Erosion for Sustainability), identifying soil erosion "hotspots" in the Manupali River watershed

  19. Specific modifications of histone tails, but not DNA methylation, mirror the temporal variation of mammalian recombination hotspots.

    Science.gov (United States)

    Zeng, Jia; Yi, Soojin V

    2014-10-16

    Recombination clusters nonuniformly across mammalian genomes at discrete genomic loci referred to as recombination hotspots. Despite their ubiquitous presence, individual hotspots rapidly lose their activities, and the molecular and evolutionary mechanisms underlying such frequent hotspot turnovers (the so-called "recombination hotspot paradox") remain unresolved. Even though some sequence motifs are significantly associated with hotspots, multiple lines of evidence indicate that factors other than underlying sequences, such as epigenetic modifications, may affect the evolution of recombination hotspots. Thus, identifying epigenetic factors that covary with recombination at fine-scale is a promising step for this important research area. It was previously reported that recombination rates correlate with indirect measures of DNA methylation in the human genome. Here, we analyze experimentally determined DNA methylation and histone modification of human sperms, and show that the correlation between DNA methylation and recombination in long-range windows does not hold with respect to the spatial and temporal variation of recombination at hotspots. On the other hand, two histone modifications (H3K4me3 and H3K27me3) overlap extensively with recombination hotspots. Similar trends were observed in mice. These results indicate that specific histone modifications rather than DNA methylation are associated with the rapid evolution of recombination hotspots. Furthermore, many human recombination hotspots occupy "bivalent" chromatin regions that harbor both active (H3K4me3) and repressive (H3K27me3) marks. This may explain why human recombination hotspots tend to occur in nongenic regions, in contrast to yeast and Arabidopsis hotspots that are characterized by generally active chromatins. Our results highlight the dynamic epigenetic underpinnings of recombination hotspot evolution. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for

  20. Global mammal distributions, biodiversity hotspots, and conservation.

    Science.gov (United States)

    Ceballos, Gerardo; Ehrlich, Paul R

    2006-12-19

    Hotspots, which have played a central role in the selection of sites for reserves, require careful rethinking. We carried out a global examination of distributions of all nonmarine mammals to determine patterns of species richness, endemism, and endangerment, and to evaluate the degree of congruence among hotspots of these three measures of diversity in mammals. We then compare congruence of hotspots in two animal groups (mammals and birds) to assess the generality of these patterns. We defined hotspots as the richest 2.5% of cells in a global equal-area grid comparable to 1 degrees latitude x 1 degrees longitude. Hotspots of species richness, "endemism," and extinction threat were noncongruent. Only 1% of cells and 16% of species were common to the three types of mammalian hotspots. Congruence increased with increases in both the geographic scope of the analysis and the percentage of cells defined as being hotspots. The within-mammal hotspot noncongruence was similar to the pattern recently found for birds. Thus, assigning global conservation priorities based on hotspots is at best a limited strategy.

  1. Differential Lectin Binding Patterns Identify Distinct Heart Regions in Giant Danio (Devario aequipinnatus) and Zebrafish (Danio rerio) Hearts

    Science.gov (United States)

    Manalo, Trina; May, Adam; Quinn, Joshua; Lafontant, Dominique S.; Shifatu, Olubusola; He, Wei; Gonzalez-Rosa, Juan M.; Burns, Geoffrey C.; Burns, Caroline E.; Burns, Alan R.; Lafontant, Pascal J.

    2016-01-01

    Lectins are carbohydrate-binding proteins commonly used as biochemical and histochemical tools to study glycoconjugate (glycoproteins, glycolipids) expression patterns in cells, tissues, including mammalian hearts. However, lectins have received little attention in zebrafish (Danio rerio) and giant danio (Devario aequipinnatus) heart studies. Here, we sought to determine the binding patterns of six commonly used lectins—wheat germ agglutinin (WGA), Ulex europaeus agglutinin, Bandeiraea simplicifolia lectin (BS lectin), concanavalin A (Con A), Ricinus communis agglutinin I (RCA I), and Lycopersicon esculentum agglutinin (tomato lectin)—in these hearts. Con A showed broad staining in the myocardium. WGA stained cardiac myocyte borders, with binding markedly stronger in the compact heart and bulbus. BS lectin, which stained giant danio coronaries, was used to measure vascular reconstruction during regeneration. However, BS lectin reacted poorly in zebrafish. RCA I stained the compact heart of both fish. Tomato lectin stained the giant danio, and while low reactivity was seen in the zebrafish ventricle, staining was observed in their transitional cardiac myocytes. In addition, we observed unique staining patterns in the developing zebrafish heart. Lectins’ ability to reveal differential glycoconjugate expression in giant danio and zebrafish hearts suggests they can serve as simple but important tools in studies of developing, adult, and regenerating fish hearts. PMID:27680670

  2. Future hotspots of terrestrial mammal loss

    Science.gov (United States)

    Visconti, Piero; Pressey, Robert L.; Giorgini, Daniele; Maiorano, Luigi; Bakkenes, Michel; Boitani, Luigi; Alkemade, Rob; Falcucci, Alessandra; Chiozza, Federica; Rondinini, Carlo

    2011-01-01

    Current levels of endangerment and historical trends of species and habitats are the main criteria used to direct conservation efforts globally. Estimates of future declines, which might indicate different priorities than past declines, have been limited by the lack of appropriate data and models. Given that much of conservation is about anticipating and responding to future threats, our inability to look forward at a global scale has been a major constraint on effective action. Here, we assess the geography and extent of projected future changes in suitable habitat for terrestrial mammals within their present ranges. We used a global earth-system model, IMAGE, coupled with fine-scale habitat suitability models and parametrized according to four global scenarios of human development. We identified the most affected countries by 2050 for each scenario, assuming that no additional conservation actions other than those described in the scenarios take place. We found that, with some exceptions, most of the countries with the largest predicted losses of suitable habitat for mammals are in Africa and the Americas. African and North American countries were also predicted to host the most species with large proportional global declines. Most of the countries we identified as future hotspots of terrestrial mammal loss have little or no overlap with the present global conservation priorities, thus confirming the need for forward-looking analyses in conservation priority setting. The expected growth in human populations and consumption in hotspots of future mammal loss mean that local conservation actions such as protected areas might not be sufficient to mitigate losses. Other policies, directed towards the root causes of biodiversity loss, are required, both in Africa and other parts of the world. PMID:21844048

  3. Threats from climate change to terrestrial vertebrate hotspots in Europe.

    Science.gov (United States)

    Maiorano, Luigi; Amori, Giovanni; Capula, Massimo; Falcucci, Alessandra; Masi, Monica; Montemaggiori, Alessandro; Pottier, Julien; Psomas, Achilleas; Rondinini, Carlo; Russo, Danilo; Zimmermann, Niklaus E; Boitani, Luigi; Guisan, Antoine

    2013-01-01

    We identified hotspots of terrestrial vertebrate species diversity in Europe and adjacent islands. Moreover, we assessed the extent to which by the end of the 21(st) century such hotspots will be exposed to average monthly temperature and precipitation patterns which can be regarded as extreme if compared to the climate experienced during 1950-2000. In particular, we considered the entire European sub-continent plus Turkey and a total of 1149 species of terrestrial vertebrates. For each species, we developed species-specific expert-based distribution models (validated against field data) which we used to calculate species richness maps for mammals, breeding birds, amphibians, and reptiles. Considering four global circulation model outputs and three emission scenarios, we generated an index of risk of exposure to extreme climates, and we used a bivariate local Moran's I to identify the areas with a significant association between hotspots of diversity and high risk of exposure to extreme climates. Our results outline that the Mediterranean basin represents both an important hotspot for biodiversity and especially for threatened species for all taxa. In particular, the Iberian and Italian peninsulas host particularly high species richness as measured over all groups, while the eastern Mediterranean basin is particularly rich in amphibians and reptiles; the islands (both Macaronesian and Mediterranean) host the highest richness of threatened species for all taxa occurs. Our results suggest that the main hotspots of biodiversity for terrestrial vertebrates may be extensively influenced by the climate change projected to occur over the coming decades, especially in the Mediterranean bioregion, posing serious concerns for biodiversity conservation.

  4. The prevalence of toxic hotspots in former Soviet countries.

    Science.gov (United States)

    Sharov, Petr; Dowling, Russell; Gogishvili, Megi; Jones, Barbara; Caravanos, Jack; McCartor, Andrew; Kashdan, Zachary; Fuller, Richard

    2016-04-01

    Using a global database of contaminated sites, toxic hotspots in eight former Soviet countries were analyzed to identify the prevalence, types and sources of toxic pollution, as well as their associated potential public health impacts. For this analysis, polluted sites in Armenia, Azerbaijan, Kazakhstan, Kyrgyzstan, Russia, Tajikistan, Ukraine, and Uzbekistan were compiled and analyzed. The levels of contamination of seven key pollutants were assessed in each country. 424 contaminated sites were identified using data from Blacksmith Institute. Pesticides, lead (Pb), radioactive metals, arsenic (As), mercury (Hg), chromium (Cr), and cadmium (Cd) were the most commonly identified key pollutants. Collectively, these sites pose health risks to an estimated 6.2 million residents. The existing data on toxic hotspots in former Soviet countries likely captures only a small percentage of actual contaminated sites, but suggests potentially severe public health consequences. Additional assessments are needed to understand the risks posed by toxic pollution in the region. Copyright © 2016. Published by Elsevier Ltd.

  5. CONSERVATION. Genetic assignment of large seizures of elephant ivory reveals Africa's major poaching hotspots.

    Science.gov (United States)

    Wasser, S K; Brown, L; Mailand, C; Mondol, S; Clark, W; Laurie, C; Weir, B S

    2015-07-03

    Poaching of elephants is now occurring at rates that threaten African populations with extinction. Identifying the number and location of Africa's major poaching hotspots may assist efforts to end poaching and facilitate recovery of elephant populations. We genetically assign origin to 28 large ivory seizures (≥0.5 metric tons) made between 1996 and 2014, also testing assignment accuracy. Results suggest that the major poaching hotspots in Africa may be currently concentrated in as few as two areas. Increasing law enforcement in these two hotspots could help curtail future elephant losses across Africa and disrupt this organized transnational crime. Copyright © 2015, American Association for the Advancement of Science.

  6. High throughput testing of the SV40 Large T antigen binding to cellular p53 identifies putative drugs for the treatment of SV40-related cancers

    International Nuclear Information System (INIS)

    Carbone, Michele; Rudzinski, Jennifer; Bocchetta, Maurizio

    2003-01-01

    SV40 has been linked to some human malignancies, and the evidence that this virus plays a causative role in mesothelioma and brain tumors is mounting. The major SV40 oncoprotein is the Large tumor antigen (Tag). A key Tag transforming activity is connected to its capability to bind and inactivate cellular p53. In this study we developed an effective, high throughput, ELISA-based method to study Tag-p53 interaction in vitro. This assay allowed us to screen a chemical library and to identify a chemical inhibitor of the Tag binding to p53. We propose that our in vitro assay is a useful method to identify molecules that may be used as therapeutic agents for the treatment of SV40-related human cancers

  7. All Hazard Hotspots/Population Density

    Indian Academy of Sciences (India)

    This map shows hotspots of humanitarian risk for floods, cyclones, and drought overlaying a population density gradient. Blue areas with striped overlay represent areas of high population density that are also risk hotspots. These are at higher risk of future population displacement as a result of climate hazards.

  8. SequenceLDhot: detecting recombination hotspots.

    Science.gov (United States)

    Fearnhead, Paul

    2006-12-15

    There is much local variation in recombination rates across the human genome--with the majority of recombination occurring in recombination hotspots--short regions of around approximately 2 kb in length that have much higher recombination rates than neighbouring regions. Knowledge of this local variation is important, e.g. in the design and analysis of association studies for disease genes. Population genetic data, such as that generated by the HapMap project, can be used to infer the location of these hotspots. We present a new, efficient and powerful method for detecting recombination hotspots from population data. We compare our method with four current methods for detecting hotspots. It is orders of magnitude quicker, and has greater power, than two related approaches. It appears to be more powerful than HotspotFisher, though less accurate at inferring the precise positions of the hotspot. It was also more powerful than LDhot in some situations: particularly for weaker hotspots (10-40 times the background rate) when SNP density is lower (maths.lancs.ac.uk/~fearnhea/Hotspot.

  9. A FRET-based high throughput screening assay to identify inhibitors of anthrax protective antigen binding to capillary morphogenesis gene 2 protein.

    Directory of Open Access Journals (Sweden)

    Michael S Rogers

    Full Text Available Anti-angiogenic therapies are effective for the treatment of cancer, a variety of ocular diseases, and have potential benefits in cardiovascular disease, arthritis, and psoriasis. We have previously shown that anthrax protective antigen (PA, a non-pathogenic component of anthrax toxin, is an inhibitor of angiogenesis, apparently as a result of interaction with the cell surface receptors capillary morphogenesis gene 2 (CMG2 protein and tumor endothelial marker 8 (TEM8. Hence, molecules that bind the anthrax toxin receptors may be effective to slow or halt pathological vascular growth. Here we describe development and testing of an effective homogeneous steady-state fluorescence resonance energy transfer (FRET high throughput screening assay designed to identify molecules that inhibit binding of PA to CMG2. Molecules identified in the screen can serve as potential lead compounds for the development of anti-angiogenic and anti-anthrax therapies. The assay to screen for inhibitors of this protein-protein interaction is sensitive and robust, with observed Z' values as high as 0.92. Preliminary screens conducted with a library of known bioactive compounds identified tannic acid and cisplatin as inhibitors of the PA-CMG2 interaction. We have confirmed that tannic acid both binds CMG2 and has anti-endothelial properties. In contrast, cisplatin appears to inhibit PA-CMG2 interaction by binding both PA and CMG2, and observed cisplatin anti-angiogenic effects are not mediated by interaction with CMG2. This work represents the first reported high throughput screening assay targeting CMG2 to identify possible inhibitors of both angiogenesis and anthrax intoxication.

  10. Ligand-bound Structures and Site-directed Mutagenesis Identify the Acceptor and Secondary Binding Sites of Streptomyces coelicolor Maltosyltransferase GlgE*

    Science.gov (United States)

    Syson, Karl; Stevenson, Clare E. M.; Miah, Farzana; Barclay, J. Elaine; Tang, Minhong; Gorelik, Andrii; Rashid, Abdul M.; Lawson, David M.; Bornemann, Stephen

    2016-01-01

    GlgE is a maltosyltransferase involved in α-glucan biosynthesis in bacteria that has been genetically validated as a target for tuberculosis therapies. Crystals of the Mycobacterium tuberculosis enzyme diffract at low resolution so most structural studies have been with the very similar Streptomyces coelicolor GlgE isoform 1. Although the donor binding site for α-maltose 1-phosphate had been previously structurally defined, the acceptor site had not. Using mutagenesis, kinetics, and protein crystallography of the S. coelicolor enzyme, we have now identified the +1 to +6 subsites of the acceptor/product, which overlap with the known cyclodextrin binding site. The sugar residues in the acceptor subsites +1 to +5 are oriented such that they disfavor the binding of malto-oligosaccharides that bear branches at their 6-positions, consistent with the known acceptor chain specificity of GlgE. A secondary binding site remote from the catalytic center was identified that is distinct from one reported for the M. tuberculosis enzyme. This new site is capable of binding a branched α-glucan and is most likely involved in guiding acceptors toward the donor site because its disruption kinetically compromises the ability of GlgE to extend polymeric substrates. However, disruption of this site, which is conserved in the Streptomyces venezuelae GlgE enzyme, did not affect the growth of S. venezuelae or the structure of the polymeric product. The acceptor subsites +1 to +4 in the S. coelicolor enzyme are well conserved in the M. tuberculosis enzyme so their identification could help inform the design of inhibitors with therapeutic potential. PMID:27531751

  11. Microbial hotspots and hot moments in soil

    Science.gov (United States)

    Kuzyakov, Yakov; Blagodatskaya, Evgenia

    2015-04-01

    Soils are the most heterogeneous parts of the biosphere, with an extremely high differentiation of properties and processes within nano- to macroscales. The spatial and temporal heterogeneity of input of labile organics by plants creates microbial hotspots over short periods of time - the hot moments. We define microbial hotspots as small soil volumes with much faster process rates and much more intensive interactions compared to the average soil conditions. Such hotspots are found in the rhizosphere, detritusphere, biopores (including drilosphere) and on aggregate surfaces, but hotspots are frequently of mixed origin. Hot moments are short-term events or sequences of events inducing accelerated process rates as compared to the averaged rates. Thus, hotspots and hot moments are defined by dynamic characteristics, i.e. by process rates. For this hotspot concept we extensively reviewed and examined the localization and size of hotspots, spatial distribution and visualization approaches, transport of labile C to and from hotspots, lifetime and process intensities, with a special focus on process rates and microbial activities. The fraction of active microorganisms in hotspots is 2-20 times higher than in the bulk soil, and their specific activities (i.e. respiration, microbial growth, mineralization potential, enzyme activities, RNA/DNA ratio) may also be much higher. The duration of hot moments in the rhizosphere is limited and is controlled by the length of the input of labile organics. It can last a few hours up to a few days. In the detritusphere, however, the duration of hot moments is regulated by the output - by decomposition rates of litter - and lasts for weeks and months. Hot moments induce succession in microbial communities and intense intra- and interspecific competition affecting C use efficiency, microbial growth and turnover. The faster turnover and lower C use efficiency in hotspots counterbalances the high C inputs, leading to the absence of strong

  12. Simulations of hydrogen sorption in rht-MOF-1: identifying the binding sites through explicit polarization and quantum rotation calculations

    KAUST Repository

    Pham, Tony

    2014-01-01

    Grand canonical Monte Carlo (GCMC) simulations of hydrogen sorption were performed in rht-MOF-1, a metal-organic framework (MOF) that consists of isophthalate groups joined by copper paddlewheel clusters and Cu3O trimers through tetrazolate moeities. This is a charged rht-MOF that contains extra-framework nitrate counterions within the material. For the simulations performed herein, excellent agreement with experiment was achieved for the simulated hydrogen sorption isotherms and calculated isosteric heat of adsorption, Qst, values only when using a polarizable potential. Thermodynamic agreement is demonstrated via comparing to experimental isotherms and binding sites are revealed by combining simulation and inelastic neutron scattering (INS) data. Simulations involving explicit many-body polarization interactions assisted in the determination of the binding sites in rht-MOF-1 through the distribution of the induced dipoles that led to strong adsorbate interactions. Four distinct hydrogen sorption sites were determined from the polarization distribution: the nitrate ions located in the corners of the truncated tetrahedral cages, the Cu2+ ions of the paddlewheels that project into the truncated tetrahedral and truncated octahedral cages (Cu1 ions), the Cu2+ ions of the Cu3O trimers (Cu3 ions), and the sides of the paddlewheels in the cuboctahedral cage. The simulations revealed that the initial sorption sites for hydrogen in rht-MOF-1 are the nitrate ions; this site corresponds to the high initial Qst value for hydrogen (9.5 kJ mol-1) in the MOF. The radial distribution functions, g(r), about the Cu2+ ions at various loadings revealed that the Cu1 ions are the preferred open-metal sorption sites for hydrogen at low loading, while the Cu3 ions become occupied at higher loadings. The validation of the aforementioned sorption sites in rht-MOF-1 was confirmed by calculating the two-dimensional quantum rotational levels about each site and comparing the levels to the

  13. Advanced in-production hotspot prediction and monitoring with micro-topography

    Science.gov (United States)

    Fanton, P.; Hasan, T.; Lakcher, A.; Le-Gratiet, B.; Prentice, C.; Simiz, J.-G.; La Greca, R.; Depre, L.; Hunsche, S.

    2017-03-01

    At 28nm technology node and below, hot spot prediction and process window control across production wafers have become increasingly critical to prevent hotspots from becoming yield-limiting defects. We previously established proof of concept for a systematic approach to identify the most critical pattern locations, i.e. hotspots, in a reticle layout by computational lithography and combining process window characteristics of these patterns with across-wafer process variation data to predict where hotspots may become yield impacting defects [1,2]. The current paper establishes the impact of micro-topography on a 28nm metal layer, and its correlation with hotspot best focus variations across a production chip layout. Detailed topography measurements are obtained from an offline tool, and pattern-dependent best focus (BF) shifts are determined from litho simulations that include mask-3D effects. We also establish hotspot metrology and defect verification by SEM image contour extraction and contour analysis. This enables detection of catastrophic defects as well as quantitative characterization of pattern variability, i.e. local and global CD uniformity, across a wafer to establish hotspot defect and variability maps. Finally, we combine defect prediction and verification capabilities for process monitoring by on-product, guided hotspot metrology, i.e. with sampling locations being determined from the defect prediction model and achieved prediction accuracy (capture rate) around 75%

  14. Hotspots for Nitrogen and Phosphorus Losses from Food Production in China: A County-Scale Analysis.

    Science.gov (United States)

    Wang, Mengru; Ma, Lin; Strokal, Maryna; Ma, Wenqi; Liu, Xuejun; Kroeze, Carolien

    2018-04-27

    Food production in China results in large losses of nitrogen (N) and phosphorus (P) to the environment. Our objective is to identify hotspots for N and P losses to the environment from food production in China at the county scale. To do this, we used the NUFER (Nutrient flows in Food chains, Environment and Resources use) model. Between 1990 and 2012, the hotspot area expanded by a factor of 3 for N, and 24 for P. In 2012 most hotspots were found in the North China Plain. Hotspots covered less than 10% of the Chinese land area, but contributed by more than half to N and P losses to the environment. Direct discharge of animal manure to rivers was an important cause of N and P losses. Food production was found to be more intensive in hotspots than in other counties. Synthetic fertilizer use and animal numbers in hotspots were a factor of 4-5 higher than in other counties in 2012. Also the number of people working in food production and the incomes of farmers are higher in hotspots than in other counties. This study concludes with suggestions for region-specific pollution control technologies for food production in China.

  15. Recombinational hotspot specific to female meiosis in the mouse major histocompatibility complex.

    Science.gov (United States)

    Shiroishi, T; Hanzawa, N; Sagai, T; Ishiura, M; Gojobori, T; Steinmetz, M; Moriwaki, K

    1990-01-01

    The wm7 haplotype of the major histocompatibility complex (MHC), derived from the Japanese wild mouse Mus musculus molossinus, enhances recombination specific to female meiosis in the K/A beta interval of the MHC. We have mapped crossover points of fifteen independent recombinants from genetic crosses of the wm7 and laboratory haplotypes. Most of them were confined to a short segment of approximately 1 kilobase (kb) of DNA between the A beta 3 and A beta 2 genes, indicating the presence of a female-specific recombinational hotspot. Its location overlaps with a sex-independent hotspot previously identified in the Mus musculus castaneus CAS3 haplotype. We have cloned and sequenced DNA fragments surrounding the hotspot from the wm7 haplotype and the corresponding regions from the hotspot-negative B10.A and C57BL/10 strains. There is no significant difference between the sequences of these three strains, or between these and the published sequences of the CAS3 and C57BL/6 strains. However, a comparison of this A beta 3/A beta 2 hotspot with a previously characterized hotspot in the E beta gene revealed that they have a very similar molecular organization. Each hotspot consists of two elements, the consensus sequence of the mouse middle repetitive MT family and the tetrameric repeated sequences, which are separated by 1 kb of DNA.

  16. Prediction of Protein Hotspots from Whole Protein Sequences by a Random Projection Ensemble System

    Directory of Open Access Journals (Sweden)

    Jinjian Jiang

    2017-07-01

    Full Text Available Hotspot residues are important in the determination of protein-protein interactions, and they always perform specific functions in biological processes. The determination of hotspot residues is by the commonly-used method of alanine scanning mutagenesis experiments, which is always costly and time consuming. To address this issue, computational methods have been developed. Most of them are structure based, i.e., using the information of solved protein structures. However, the number of solved protein structures is extremely less than that of sequences. Moreover, almost all of the predictors identified hotspots from the interfaces of protein complexes, seldom from the whole protein sequences. Therefore, determining hotspots from whole protein sequences by sequence information alone is urgent. To address the issue of hotspot predictions from the whole sequences of proteins, we proposed an ensemble system with random projections using statistical physicochemical properties of amino acids. First, an encoding scheme involving sequence profiles of residues and physicochemical properties from the AAindex1 dataset is developed. Then, the random projection technique was adopted to project the encoding instances into a reduced space. Then, several better random projections were obtained by training an IBk classifier based on the training dataset, which were thus applied to the test dataset. The ensemble of random projection classifiers is therefore obtained. Experimental results showed that although the performance of our method is not good enough for real applications of hotspots, it is very promising in the determination of hotspot residues from whole sequences.

  17. Hotspots for Nitrogen and Phosphorus Losses from Food Production in China: A County-Scale Analysis

    Science.gov (United States)

    2018-01-01

    Food production in China results in large losses of nitrogen (N) and phosphorus (P) to the environment. Our objective is to identify hotspots for N and P losses to the environment from food production in China at the county scale. To do this, we used the NUFER (Nutrient flows in Food chains, Environment and Resources use) model. Between 1990 and 2012, the hotspot area expanded by a factor of 3 for N, and 24 for P. In 2012 most hotspots were found in the North China Plain. Hotspots covered less than 10% of the Chinese land area, but contributed by more than half to N and P losses to the environment. Direct discharge of animal manure to rivers was an important cause of N and P losses. Food production was found to be more intensive in hotspots than in other counties. Synthetic fertilizer use and animal numbers in hotspots were a factor of 4–5 higher than in other counties in 2012. Also the number of people working in food production and the incomes of farmers are higher in hotspots than in other counties. This study concludes with suggestions for region-specific pollution control technologies for food production in China. PMID:29671326

  18. Monitoring the trajectory of urban nighttime light hotspots using a Gaussian volume model

    Science.gov (United States)

    Zheng, Qiming; Jiang, Ruowei; Wang, Ke; Huang, Lingyan; Ye, Ziran; Gan, Muye; Ji, Biyong

    2018-03-01

    Urban nighttime light hotspot is an ideal representation of the spatial heterogeneity of human activities within a city, which is sensitive to regional urban expansion pattern. However, most of previous studies related to nighttime light imageries focused on extracting urban extent, leaving the spatial variation of radiance intensity insufficiently explored. With the help of global radiance calibrated DMSP-OLS datasets (NTLgrc), we proposed an innovative framework to explore the spatio-temporal trajectory of polycentric urban nighttime light hotspots. Firstly, NTLgrc was inter-annually calibrated to improve the consistency. Secondly, multi-resolution segmentation and region-growing SVM classification were employed to remove blooming effect and to extract potential clusters. At last, the urban hotspots were identified by a Gaussian volume model, and the resulting parameters were used to quantitatively depict hotspot features (i.e., intensity, morphology and centroid dynamics). The result shows that our framework successfully captures hotspots in polycentric urban area, whose Ra2 are over 0.9. Meanwhile, the spatio-temporal dynamics of the hotspot features intuitively reveal the impact of the regional urban growth pattern and planning strategies on human activities. Compared to previous studies, our framework is more robust and offers an effective way to describe hotspot pattern. Also, it provides a more comprehensive and spatial-explicit understanding regarding the interaction between urbanization pattern and human activities. Our findings are expected to be beneficial to governors in term of sustainable urban planning and decision making.

  19. A triad of lys12, lys41, arg78 spatial domain, a novel identified heparin binding site on tat protein, facilitates tat-driven cell adhesion.

    Directory of Open Access Journals (Sweden)

    Jing Ai

    Full Text Available Tat protein, released by HIV-infected cells, has a battery of important biological effects leading to distinct AIDS-associated pathologies. Cell surface heparan sulfate protoglycans (HSPGs have been accepted as endogenous Tat receptors, and the Tat basic domain has been identified as the heparin binding site. However, findings that deletion or substitution of the basic domain inhibits but does not completely eliminate Tat-heparin interactions suggest that the basic domain is not the sole Tat heparin binding site. In the current study, an approach integrating computational modeling, mutagenesis, biophysical and cell-based assays was used to elucidate a novel, high affinity heparin-binding site: a Lys12, Lys41, Arg78 (KKR spatial domain. This domain was also found to facilitate Tat-driven β1 integrin activation, producing subsequent SLK cell adhesion in an HSPG-dependent manner, but was not involved in Tat internalization. The identification of this new heparin binding site may foster further insight into the nature of Tat-heparin interactions and subsequent biological functions, facilitating the rational design of new therapeutics against Tat-mediated pathological events.

  20. Application of GIS to predict malaria hotspots based on Anopheles arabiensis habitat suitability in Southern Africa

    Science.gov (United States)

    Gwitira, Isaiah; Murwira, Amon; Zengeya, Fadzai M.; Shekede, Munyaradzi Davis

    2018-02-01

    Malaria remains a major public health problem and a principal cause of morbidity and mortality in most developing countries. Although malaria still presents health problems, significant successes have been recorded in reducing deaths resulting from the disease. As malaria transmission continues to decline, control interventions will increasingly depend on the ability to define high-risk areas known as malaria hotspots. Therefore, there is urgent need to use geospatial tools such as geographic information system to detect spatial patterns of malaria and delineate disease hot spots for better planning and management. Thus, accurate mapping and prediction of seasonality of malaria hotspots is an important step towards developing strategies for effective malaria control. In this study, we modelled seasonal malaria hotspots as a function of habitat suitability of Anopheles arabiensis (A. Arabiensis) as a first step towards predicting likely seasonal malaria hotspots that could provide guidance in targeted malaria control. We used Geographical information system (GIS) and spatial statistic methods to identify seasonal hotspots of malaria cases at the country level. In order to achieve this, we first determined the spatial distribution of seasonal malaria hotspots using the Getis Ord Gi* statistic based on confirmed positive malaria cases recorded at health facilities in Zimbabwe over four years (1996-1999). We then used MAXENT technique to model habitat suitability of A. arabiensis from presence data collected from 1990 to 2002 based on bioclimatic variables and altitude. Finally, we used autologistic regression to test the extent to which malaria hotspots can be predicted using A. arabiensis habitat suitability. Our results show that A. arabiensis habitat suitability consistently and significantly (p < 0.05) predicts malaria hotspots from 1996 to 1999. Overall, our results show that malaria hotspots can be predicted using A. arabiensis habitat suitability, suggesting

  1. Monoclonal antibody OKB7, which identifies the 14OKd complement receptor type 2 (CR/sub 2/), also identifies a 72Kd secreted fragment of CR/sub 2/ that contains the C3d-binding site

    Energy Technology Data Exchange (ETDEWEB)

    Myones, B.L.; Ross, G.D.

    1986-03-05

    CR/sub 2/ is a 140-145Kd glycoprotein expressed on B lymphocytes which binds both C3d and Epstein-Barr virus (EBV). OKB7, an IgG/sub 2a/ monoclonal antibody to CR/sub 2/, blocks C3d and EBV binding, while HB-5, another monoclonal IgG/sub 2a/ anti-CR/sub 2/, does not. A 72Kd C3d-binding glycoprotein (gp72), isolated from Raji cell media, was previously thought to be CR/sub 2/ because a polyclonal rabbit anti-gp72 inhibited EC3d rosettes. ELISA assay demonstrated that OKB7, but not HB-5, bound to purified gp72 fixed to microtiter wells. Insoluble and soluble gp72 blocked Raji cell uptake of /sup 125/I-labeled OKB7, but not labeled anti-B2 or HB-5. Rabbit anti-gp72 immunoprecipitated bands at 140Kd and 72Kd from /sup 125/I-labelled and solubilized B cell membranes. Culture media from Raji cells grown in the presence /sup 3/H-labeled amino acids was sequentially immunoprecipitated by irrelevant antibody, OKB7, and HB-5. A single 72Kd radiolabeled band was demonstrated only with OKB7, and this was identical to that produced by the immunoprecipitation of /sup 125/I-labeled gp72 with rabbit anti-gp72. Thus, OKB7, which identifies the 140Kd CR/sub 2/ molecule, also identifies a 72Kd shed fragment of CR/sub 2/ isolated from Raji cell media, which contains the C3d-binding site.

  2. Monoclonal antibody OKB7, which identifies the 14OKd complement receptor type 2 (CR2), also identifies a 72Kd secreted fragment of CR2 that contains the C3d-binding site

    International Nuclear Information System (INIS)

    Myones, B.L.; Ross, G.D.

    1986-01-01

    CR 2 is a 140-145Kd glycoprotein expressed on B lymphocytes which binds both C3d and Epstein-Barr virus (EBV). OKB7, an IgG/sub 2a/ monoclonal antibody to CR 2 , blocks C3d and EBV binding, while HB-5, another monoclonal IgG/sub 2a/ anti-CR 2 , does not. A 72Kd C3d-binding glycoprotein (gp72), isolated from Raji cell media, was previously thought to be CR 2 because a polyclonal rabbit anti-gp72 inhibited EC3d rosettes. ELISA assay demonstrated that OKB7, but not HB-5, bound to purified gp72 fixed to microtiter wells. Insoluble and soluble gp72 blocked Raji cell uptake of 125 I-labeled OKB7, but not labeled anti-B2 or HB-5. Rabbit anti-gp72 immunoprecipitated bands at 140Kd and 72Kd from 125 I-labelled and solubilized B cell membranes. Culture media from Raji cells grown in the presence 3 H-labeled amino acids was sequentially immunoprecipitated by irrelevant antibody, OKB7, and HB-5. A single 72Kd radiolabeled band was demonstrated only with OKB7, and this was identical to that produced by the immunoprecipitation of 125 I-labeled gp72 with rabbit anti-gp72. Thus, OKB7, which identifies the 140Kd CR 2 molecule, also identifies a 72Kd shed fragment of CR 2 isolated from Raji cell media, which contains the C3d-binding site

  3. Capturing Hotspots For Constrained Indoor Movement

    DEFF Research Database (Denmark)

    Ahmed, Tanvir; Pedersen, Torben Bach; Lu, Hua

    2013-01-01

    Finding the hotspots in large indoor spaces is very important for getting overloaded locations, security, crowd management, indoor navigation and guidance. The tracking data coming from indoor tracking are huge in volume and not readily available for finding hotspots. This paper presents a graph......-based model for constrained indoor movement that can map the tracking records into mapping records which represent the entry and exit times of an object in a particular location. Then it discusses the hotspots extraction technique from the mapping records....

  4. Putting 'Local' Back into Public Wifi Hotspots

    DEFF Research Database (Denmark)

    Korn, Matthias; Klokmose, Clemens Nylandsted

    2012-01-01

    Public Wifi hotspots in cafes and public places are based on wireless local area network technology (WLAN). In contrast to the common understanding of connecting directly to the internet when connecting to a Wifi hotspot, we are proposing to bring the original notion of connecting to a local...... hotspot in cafes, bars, community centers, and other (semi-)public places in order to facilitate co-located activities for such varied purposes as fostering local community, civic participation, sociality in general, and entertainment. We propose a network locality that builds on local infrastructure...

  5. Rational identification of aggregation hotspots based on secondary structure and amino acid hydrophobicity.

    Science.gov (United States)

    Matsui, Daisuke; Nakano, Shogo; Dadashipour, Mohammad; Asano, Yasuhisa

    2017-08-25

    Insolubility of proteins expressed in the Escherichia coli expression system hinders the progress of both basic and applied research. Insoluble proteins contain residues that decrease their solubility (aggregation hotspots). Mutating these hotspots to optimal amino acids is expected to improve protein solubility. To date, however, the identification of these hotspots has proven difficult. In this study, using a combination of approaches involving directed evolution and primary sequence analysis, we found two rules to help inductively identify hotspots: the α-helix rule, which focuses on the hydrophobicity of amino acids in the α-helix structure, and the hydropathy contradiction rule, which focuses on the difference in hydrophobicity relative to the corresponding amino acid in the consensus protein. By properly applying these two rules, we succeeded in improving the probability that expressed proteins would be soluble. Our methods should facilitate research on various insoluble proteins that were previously difficult to study due to their low solubility.

  6. Role of endothelial permeability hotspots and endothelial mitosis in determining age-related patterns of macromolecule uptake by the rabbit aortic wall near branch points.

    Science.gov (United States)

    Chooi, K Yean; Comerford, Andrew; Cremers, Stephanie J; Weinberg, Peter D

    2016-07-01

    Transport of macromolecules between plasma and the arterial wall plays a key role in atherogenesis. Scattered hotspots of elevated endothelial permeability to macromolecules occur in the aorta; a fraction of them are associated with dividing cells. Hotspots occur particularly frequently downstream of branch points, where lesions develop in young rabbits and children. However, the pattern of lesions varies with age, and can be explained by similar variation in the pattern of macromolecule uptake. We investigated whether patterns of hotspots and mitosis also change with age. Evans' Blue dye-labeled albumin was injected intravenously into immature or mature rabbits and its subsequent distribution in the aortic wall around intercostal branch ostia examined by confocal microscopy and automated image analysis. Mitosis was detected by immunofluorescence after adding 5-bromo-2-deoxiuridine to drinking water. Hotspots were most frequent downstream of branches in immature rabbits, but a novel distribution was observed in mature rabbits. Neither pattern was explained by mitosis. Hotspot uptake correlated spatially with the much greater non-hotspot uptake (p hotspots were considered. The pattern of hotspots changes with age. The data are consistent with there being a continuum of local permeabilities rather than two distinct mechanisms. The distribution of the dye, which binds to elastin and collagen, was similar to that of non-binding tracers and to lesions apart from a paucity at the lateral margins of branches that can be explained by lower levels of fibrous proteins in those regions. Copyright © 2016. Published by Elsevier Ireland Ltd.

  7. In Silico Analysis of Gene Expression Network Components Underlying Pigmentation Phenotypes in the Python Identified Evolutionarily Conserved Clusters of Transcription Factor Binding Sites

    Directory of Open Access Journals (Sweden)

    Kristopher J. L. Irizarry

    2016-01-01

    Full Text Available Color variation provides the opportunity to investigate the genetic basis of evolution and selection. Reptiles are less studied than mammals. Comparative genomics approaches allow for knowledge gained in one species to be leveraged for use in another species. We describe a comparative vertebrate analysis of conserved regulatory modules in pythons aimed at assessing bioinformatics evidence that transcription factors important in mammalian pigmentation phenotypes may also be important in python pigmentation phenotypes. We identified 23 python orthologs of mammalian genes associated with variation in coat color phenotypes for which we assessed the extent of pairwise protein sequence identity between pythons and mouse, dog, horse, cow, chicken, anole lizard, and garter snake. We next identified a set of melanocyte/pigment associated transcription factors (CREB, FOXD3, LEF-1, MITF, POU3F2, and USF-1 that exhibit relatively conserved sequence similarity within their DNA binding regions across species based on orthologous alignments across multiple species. Finally, we identified 27 evolutionarily conserved clusters of transcription factor binding sites within ~200-nucleotide intervals of the 1500-nucleotide upstream regions of AIM1, DCT, MC1R, MITF, MLANA, OA1, PMEL, RAB27A, and TYR from Python bivittatus. Our results provide insight into pigment phenotypes in pythons.

  8. Understanding the Functionality of Human Activity Hotspots from Their Scaling Pattern Using Trajectory Data

    Directory of Open Access Journals (Sweden)

    Tao Jia

    2017-11-01

    Full Text Available Human activity hotspots are the clusters of activity locations in space and time, and a better understanding of their functionality would be useful for urban land use planning and transportation. In this article, using trajectory data, we aim to infer the functionality of human activity hotspots from their scaling pattern in a reliable way. Specifically, a large number of stopping locations are extracted from trajectory data, which are then aggregated into activity hotspots. Activity hotspots are found to display scaling patterns in terms of the sublinear scaling relationships between the number of stopping locations and the number of points of interest (POIs, which indicates economies of scale of human interactions with urban land use. Importantly, this scaling pattern remains stable over time. This finding inspires us to devise an allometric ruler to identify the activity hotspots, whose functionality could be reliably estimated using the stopping locations. Thereafter, a novel Bayesian inference model is proposed to infer their urban functionality, which examines the spatial and temporal information of stopping locations covering 75 days. Experimental results suggest that the functionality of identified activity hotspots are reliably inferred by stopping locations, such as the railway station.

  9. DNA barcoding the floras of biodiversity hotspots.

    Science.gov (United States)

    Lahaye, Renaud; van der Bank, Michelle; Bogarin, Diego; Warner, Jorge; Pupulin, Franco; Gigot, Guillaume; Maurin, Olivier; Duthoit, Sylvie; Barraclough, Timothy G; Savolainen, Vincent

    2008-02-26

    DNA barcoding is a technique in which species identification is performed by using DNA sequences from a small fragment of the genome, with the aim of contributing to a wide range of ecological and conservation studies in which traditional taxonomic identification is not practical. DNA barcoding is well established in animals, but there is not yet any universally accepted barcode for plants. Here, we undertook intensive field collections in two biodiversity hotspots (Mesoamerica and southern Africa). Using >1,600 samples, we compared eight potential barcodes. Going beyond previous plant studies, we assessed to what extent a "DNA barcoding gap" is present between intra- and interspecific variations, using multiple accessions per species. Given its adequate rate of variation, easy amplification, and alignment, we identified a portion of the plastid matK gene as a universal DNA barcode for flowering plants. Critically, we further demonstrate the applicability of DNA barcoding for biodiversity inventories. In addition, analyzing >1,000 species of Mesoamerican orchids, DNA barcoding with matK alone reveals cryptic species and proves useful in identifying species listed in Convention on International Trade of Endangered Species (CITES) appendixes.

  10. Environmental and Microbial Features Affecting Denitrification and Anammox Hotspots in an Estuarine Ecosystem

    Science.gov (United States)

    Lisa, J.; Song, B.; Lefcheck, J. S.; Tobias, C. R.

    2016-02-01

    Biogeochemical hotspots are characterized as a few sites that exhibit extremely high reaction rates relative to surrounding area, and often account for a high percentage of the overall reaction rates in an ecosystem. Criteria for quantitatively identifying these sites have not been well established. Further, the underlying mechanisms of hotspots have been described in terms of environmental conditions, with little attention paid to the microbial community. The objectives of this study were to establish quantitative criteria to identify denitrification and anammox hotspots, and determine the underlying microbial and environmental factors responsible for elevated N2 production. We used 15N isotope pairing incubation experiments to measure denitrification and anammox rates in the New River Estuary, NC. Quantitative PCR assays of nitrous oxide reductase (nosZ Clades I and II) and hydrazine oxidoreductase (hzo) genes were conducted to estimate denitrifier and anammox abundance. Structural Equation Modeling (SEM) was used to elucidate complex causal relationships between environmental and biological variables. Denitrification hotspots, quantitatively defined as statistical outliers, accounted for 35.6% total denitrification while comprising only 7.3% of the sites. Anammox hotspots,10.6% of the sites, accounted for 60.9% of total anammox. SEM revealed increased sediment organics at lower salinities supported higher functional gene abundance, which in turn resulted in higher N2 production. Surprisingly, denitrification rates were significantly and positively correlated with nosZ Clade II gene abundance, after accounting for the non-significant contributions of the naturally more abundant nosZ Clade I, and other environmental covariates. This is the first time that a quantitative definition of biogeochemical hotspots was put forth and used to determine the importance of anammox and denitrification hotspots in estuarine nitrogen removal capacity. Despite the low area

  11. Ultraconfined Plasmonic Hotspots Inside Graphene Nanobubbles.

    Science.gov (United States)

    Fei, Z; Foley, J J; Gannett, W; Liu, M K; Dai, S; Ni, G X; Zettl, A; Fogler, M M; Wiederrecht, G P; Gray, S K; Basov, D N

    2016-12-14

    We report on a nanoinfrared (IR) imaging study of ultraconfined plasmonic hotspots inside graphene nanobubbles formed in graphene/hexagonal boron nitride (hBN) heterostructures. The volume of these plasmonic hotspots is more than one-million-times smaller than what could be achieved by free-space IR photons, and their real-space distributions are controlled by the sizes and shapes of the nanobubbles. Theoretical analysis indicates that the observed plasmonic hotspots are formed due to a significant increase of the local plasmon wavelength in the nanobubble regions. Such an increase is attributed to the high sensitivity of graphene plasmons to its dielectric environment. Our work presents a novel scheme for plasmonic hotspot formation and sheds light on future applications of graphene nanobubbles for plasmon-enhanced IR spectroscopy.

  12. Coral Reef Watch, Hotspots, 50 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA Coral Reef Watch provides Coral Bleaching hotspot maps derived from NOAA's Polar Operational Environmental Satellites (POES). This data provides global area...

  13. Was sind Biodiversity Hotspots - global, regional, lokal?

    OpenAIRE

    Hobohm, Carsten

    2005-01-01

    Das Konzept der Biodiversity Hotspots, das Ende der 1980er Jahre von Norman Myers entworfen wurde, gehört derzeit zu den wichtigen forschungsleitenden Ansätzen globaler Naturschutzstrategien. In der vorliegenden Arbeit geht es in erster Linie um die Frage, ob und inwiefern dieses Konzept auf die regionale und lokale Dimension Europas übertragen werden kann. Es wird ein Vorschlag unterbreitet, wie europäische Biodiversity Hotspots definiert und identifiziert werden können. Bei der Erforschung ...

  14. Evaluating Temporal Consistency in Marine Biodiversity Hotspots

    OpenAIRE

    Piacenza, Susan E.; Thurman, Lindsey L.; Barner, Allison K.; Benkwitt, Cassandra E.; Boersma, Kate S.; Cerny-Chipman, Elizabeth B.; Ingeman, Kurt E.; Kindinger, Tye L.; Lindsley, Amy J.; Nelson, Jake; Reimer, Jessica N.; Rowe, Jennifer C.; Shen, Chenchen; Thompson, Kevin A.; Heppell, Selina S.

    2015-01-01

    With the ongoing crisis of biodiversity loss and limited resources for conservation, the concept of biodiversity hotspots has been useful in determining conservation priority areas. However, there has been limited research into how temporal variability in biodiversity may influence conservation area prioritization. To address this information gap, we present an approach to evaluate the temporal consistency of biodiversity hotspots in large marine ecosystems. Using a large scale, public monito...

  15. Role of hydrodynamic instability growth in hot-spot mass gain and fusion performance of inertial confinement fusion implosions

    International Nuclear Information System (INIS)

    Srinivasan, Bhuvana; Tang, Xian-Zhu

    2014-01-01

    In an inertial confinement fusion target, energy loss due to thermal conduction from the hot-spot will inevitably ablate fuel ice into the hot-spot, resulting in a more massive but cooler hot-spot, which negatively impacts fusion yield. Hydrodynamic mix due to Rayleigh-Taylor instability at the gas-ice interface can aggravate the problem via an increased gas-ice interfacial area across which energy transfer from the hot-spot and ice can be enhanced. Here, this mix-enhanced transport effect on hot-spot fusion-performance degradation is quantified using contrasting 1D and 2D hydrodynamic simulations, and its dependence on effective acceleration, Atwood number, and ablation speed is identified

  16. The red queen model of recombination hotspots evolution in the light of archaic and modern human genomes.

    Directory of Open Access Journals (Sweden)

    Yann Lesecque

    2014-11-01

    Full Text Available Recombination is an essential process in eukaryotes, which increases diversity by disrupting genetic linkage between loci and ensures the proper segregation of chromosomes during meiosis. In the human genome, recombination events are clustered in hotspots, whose location is determined by the PRDM9 protein. There is evidence that the location of hotspots evolves rapidly, as a consequence of changes in PRDM9 DNA-binding domain. However, the reasons for these changes and the rate at which they occur are not known. In this study, we investigated the evolution of human hotspot loci and of PRDM9 target motifs, both in modern and archaic human lineages (Denisovan to quantify the dynamic of hotspot turnover during the recent period of human evolution. We show that present-day human hotspots are young: they have been active only during the last 10% of the time since the divergence from chimpanzee, starting to be operating shortly before the split between Denisovans and modern humans. Surprisingly, however, our analyses indicate that Denisovan recombination hotspots did not overlap with modern human ones, despite sharing similar PRDM9 target motifs. We further show that high-affinity PRDM9 target motifs are subject to a strong self-destructive drive, known as biased gene conversion (BGC, which should lead to the loss of the majority of them in the next 3 MYR. This depletion of PRDM9 genomic targets is expected to decrease fitness, and thereby to favor new PRDM9 alleles binding different motifs. Our refined estimates of the age and life expectancy of human hotspots provide empirical evidence in support of the Red Queen hypothesis of recombination hotspots evolution.

  17. The red queen model of recombination hotspots evolution in the light of archaic and modern human genomes.

    Science.gov (United States)

    Lesecque, Yann; Glémin, Sylvain; Lartillot, Nicolas; Mouchiroud, Dominique; Duret, Laurent

    2014-11-01

    Recombination is an essential process in eukaryotes, which increases diversity by disrupting genetic linkage between loci and ensures the proper segregation of chromosomes during meiosis. In the human genome, recombination events are clustered in hotspots, whose location is determined by the PRDM9 protein. There is evidence that the location of hotspots evolves rapidly, as a consequence of changes in PRDM9 DNA-binding domain. However, the reasons for these changes and the rate at which they occur are not known. In this study, we investigated the evolution of human hotspot loci and of PRDM9 target motifs, both in modern and archaic human lineages (Denisovan) to quantify the dynamic of hotspot turnover during the recent period of human evolution. We show that present-day human hotspots are young: they have been active only during the last 10% of the time since the divergence from chimpanzee, starting to be operating shortly before the split between Denisovans and modern humans. Surprisingly, however, our analyses indicate that Denisovan recombination hotspots did not overlap with modern human ones, despite sharing similar PRDM9 target motifs. We further show that high-affinity PRDM9 target motifs are subject to a strong self-destructive drive, known as biased gene conversion (BGC), which should lead to the loss of the majority of them in the next 3 MYR. This depletion of PRDM9 genomic targets is expected to decrease fitness, and thereby to favor new PRDM9 alleles binding different motifs. Our refined estimates of the age and life expectancy of human hotspots provide empirical evidence in support of the Red Queen hypothesis of recombination hotspots evolution.

  18. Analysis of microstructure-dependent shock dissipation and hot-spot formation in granular metalized explosive

    Science.gov (United States)

    Chakravarthy, Sunada; Gonthier, Keith A.

    2016-07-01

    Variations in the microstructure of granular explosives (i.e., particle packing density, size, shape, and composition) can affect their shock sensitivity by altering thermomechanical fields at the particle-scale during pore collapse within shocks. If the deformation rate is fast, hot-spots can form, ignite, and interact, resulting in burn at the macro-scale. In this study, a two-dimensional finite and discrete element technique is used to simulate and examine shock-induced dissipation and hot-spot formation within low density explosives (68%-84% theoretical maximum density (TMD)) consisting of large ensembles of HMX (C4H8N8O8) and aluminum (Al) particles (size ˜ 60 -360 μm). Emphasis is placed on identifying how the inclusion of Al influences effective shock dissipation and hot-spot fields relative to equivalent ensembles of neat/pure HMX for shocks that are sufficiently strong to eliminate porosity. Spatially distributed hot-spot fields are characterized by their number density and area fraction enabling their dynamics to be described in terms of nucleation, growth, and agglomeration-dominated phases with increasing shock strength. For fixed shock particle speed, predictions indicate that decreasing packing density enhances shock dissipation and hot-spot formation, and that the inclusion of Al increases dissipation relative to neat HMX by pressure enhanced compaction resulting in fewer but larger HMX hot-spots. Ensembles having bimodal particle sizes are shown to significantly affect hot-spot dynamics by altering the spatial distribution of hot-spots behind shocks.

  19. CKD hotspots around the world: where, why and what the lessons are. A CKJ review series.

    Science.gov (United States)

    Martín-Cleary, Catalina; Ortiz, Alberto

    2014-12-01

    Chronic kidney disease (CKD) is one of the three causes of death that has had the highest increase in the last 20 years. The increasing CKD burden occurs in the context of lack of access of most of the world population to adequate healthcare and an incomplete understanding of the pathogenesis of CKD. However, CKD is not homogeneously distributed. CKD hotspots are defined as countries, region, communities or ethnicities with higher than average incidence of CKD. Analysis of CKD hotspots has the potential to provide valuable insights into the pathogenesis of kidney disease and to improve the life expectancy of the affected communities. Examples include ethnicities such as African Americans in the USA or Aboriginals in Australia, regions such as certain Balkan valleys or Central America and even groups of people sharing common activities or interests such as young women trying to lose weight in Belgium. The study of these CKD hotspots has identified underlying genetic factors, such as ApoL1 gene variants, environmental toxins, such as aristolochic acid and socioeconomic factors leading to nutritional deprivation and inflammation/infection. The CKD hotspots series of CKJ reviews will explore the epidemiology and causes in CKD hotspots, beginning with Australian Aboriginals in this issue. An online map of CKD hotspots around the world will feature the reviewed hotspots, highlighting known or suspected causes as well as ongoing projects to unravel the cause and providing a directory of public health officials, physicians and basic scientists involved in these efforts. Since the high prevalence of CKD in a particular region or population may only be known to local physicians, we encourage readers to propose further CKD hotspots to be reviewed.

  20. ARG-walker: inference of individual specific strengths of meiotic recombination hotspots by population genomics analysis.

    Science.gov (United States)

    Chen, Hao; Yang, Peng; Guo, Jing; Kwoh, Chee Keong; Przytycka, Teresa M; Zheng, Jie

    2015-01-01

    Meiotic recombination hotspots play important roles in various aspects of genomics, but the underlying mechanisms for regulating the locations and strengths of recombination hotspots are not yet fully revealed. Most existing algorithms for estimating recombination rates from sequence polymorphism data can only output average recombination rates of a population, although there is evidence for the heterogeneity in recombination rates among individuals. For genome-wide association studies (GWAS) of recombination hotspots, an efficient algorithm that estimates the individualized strengths of recombination hotspots is highly desirable. In this work, we propose a novel graph mining algorithm named ARG-walker, based on random walks on ancestral recombination graphs (ARG), to estimate individual-specific recombination hotspot strengths. Extensive simulations demonstrate that ARG-walker is able to distinguish the hot allele of a recombination hotspot from the cold allele. Integrated with output of ARG-walker, we performed GWAS on the phased haplotype data of the 22 autosome chromosomes of the HapMap Asian population samples of Chinese and Japanese (JPT+CHB). Significant cis-regulatory signals have been detected, which is corroborated by the enrichment of the well-known 13-mer motif CCNCCNTNNCCNC of PRDM9 protein. Moreover, two new DNA motifs have been identified in the flanking regions of the significantly associated SNPs (single nucleotide polymorphisms), which are likely to be new cis-regulatory elements of meiotic recombination hotspots of the human genome. Our results on both simulated and real data suggest that ARG-walker is a promising new method for estimating the individual recombination variations. In the future, it could be used to uncover the mechanisms of recombination regulation and human diseases related with recombination hotspots.

  1. Re-evaluating the NO 2 hotspot over the South African Highveld

    Directory of Open Access Journals (Sweden)

    Alexandra S.M. Lourens

    2012-10-01

    Full Text Available Globally, numerous pollution hotspots have been identified using satellite-based instruments. One of these hotspots is the prominent NO2hotspot over the South African Highveld. The tropospheric NO2column density of this area is comparable to that observed for central and northern Europe, eastern North America and south-east Asia. The most well-known pollution source in this area is a large array of coal-fired power stations. Upon closer inspection, long-term means of satellite observations also show a smaller area, approximately 100 km west of the Highveld hotspot, with a seemingly less substantial NO2column density. This area correlates with the geographical location of the Johannesburg–Pretoria conurbation or megacity, one of the 40 largest metropolitan areas in the world. Ground-based measurements indicate that NO2concentrations in the megacity have diurnal peaks in the early morning and late afternoon, which coincide with peak traffic hours and domestic combustion. During these times, NO2concentrations in the megacity are higher than those in the Highveld hotspot. These diurnal NO2 peaks in the megacity have generally been overlooked by satellite observations because the satellites have fixed local overpass times that do not coincide with these peak periods. Consequently, the importance of NO2 over the megacity has been underestimated. We examined the diurnal cycles of NO2 ground-based measurements for the two areas – the megacity and the Highveld hotspot – and compared them with the satellite-based NO2 observations. Results show that the Highveld hotspot is accompanied by a second hotspot over the megacity, which is of significance for the more than 10 million people living in this megacity.

  2. Blowing dust and highway safety in the southwestern United States: Characteristics of dust emission "hotspots" and management implications.

    Science.gov (United States)

    Li, Junran; Kandakji, Tarek; Lee, Jeffrey A; Tatarko, John; Blackwell, John; Gill, Thomas E; Collins, Joe D

    2018-04-15

    Despite the widespread media attention of chain-reaction traffic incidents and property damage caused by windblown dust in the U.S. and elsewhere in the world, very few studies have provided in-depth analysis on this issue. Remote sensing and field observations reveal that wind erosion in the southwestern U.S. typically occurs in localized source areas, characterized as "hotspots", while most of the landscape is not eroding. In this study, we identified the spatial and temporal distribution patterns of hotspots that may contribute dust blowing onto highways in the southwestern U.S. We further classified the hotspots for the potential of blowing dust production based upon field observations and wind erosion modeling. Results of land use and land cover show that shrubland, grassland, and cropland accounted for 42%, 31%, and 21% of the overall study area, respectively. However, of the 620 total hotspots identified, 164 (26%), 141 (22%), and 234 (38%) are located on shrubland, grassland, and cropland, respectively. Barren land represented 0.9% of the land area but 8% of the dust hotspots. While a majority of these hotspots are located close to highways, we focused on 55 of them, which are located hotspot sites are dominated by sand and silt particles with threshold shear velocities ranging from 0.17-0.78m s -1 , largely depending on the land use of the hotspot sites. Dust emission modeling showed that 13 hotspot sites could produce annual emissions >3.79kg m -2 , yielding highly hazardous dust emissions to ground transportation with visibility hotspots are critical information for highway authorities to make informed and timely management decisions when wind events strike. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. The consequences of sequence erosion in the evolution of recombination hotspots.

    Science.gov (United States)

    Tiemann-Boege, Irene; Schwarz, Theresa; Striedner, Yasmin; Heissl, Angelika

    2017-12-19

    Meiosis is initiated by a double-strand break (DSB) introduced in the DNA by a highly controlled process that is repaired by recombination. In many organisms, recombination occurs at specific and narrow regions of the genome, known as recombination hotspots, which overlap with regions enriched for DSBs. In recent years, it has been demonstrated that conversions and mutations resulting from the repair of DSBs lead to a rapid sequence evolution at recombination hotspots eroding target sites for DSBs. We still do not fully understand the effect of this erosion in the recombination activity, but evidence has shown that the binding of trans -acting factors like PRDM9 is affected. PRDM9 is a meiosis-specific, multi-domain protein that recognizes DNA target motifs by its zinc finger domain and directs DSBs to these target sites. Here we discuss the changes in affinity of PRDM9 to eroded recognition sequences, and explain how these changes in affinity of PRDM9 can affect recombination, leading sometimes to sterility in the context of hybrid crosses. We also present experimental data showing that DNA methylation reduces PRDM9 binding in vitro Finally, we discuss PRDM9-independent hotspots, posing the question how these hotspots evolve and change with sequence erosion.This article is part of the themed issue 'Evolutionary causes and consequences of recombination rate variation in sexual organisms'. © 2017 The Authors.

  4. Identification of biodiversity hotspot in national level – Importance of unpublished data

    Directory of Open Access Journals (Sweden)

    Naruemon Tantipisanuh

    2018-01-01

    Full Text Available High priority areas for conservation are typically identified based on ad hoc methods without supporting data due to a lack of scientific resources and staff. The objective of this study was to show how unpublished data in combination with citizen science can be useful for identifying biodiversity hotspot areas using Thailand as an example. Species records were aggregated from various sources both published (records permanently archived or temporarily available on the internet and unpublished data (derived from interviews. Data from 2001 to 2016 were used to identify hotspot areas. In total, 15% of the data were obtained from personal interviews. Most Thai hotspot areas were already inside government protected areas. Amphibians and reptiles were the taxa that unpublished data had the greatest influence on hotspot identification, while this influence was least for birds. Spatial coverage of species records showed a bias toward particular regions and areas probably due to a number of factors including their international reputation and previous species records. Results from this project reveal the importance of unpublished records as a source for identifying hotspot locations especially for less studied species groups and indicates the continued need for encouraging scientists as well as amateur naturalists to report their observations to archived websites and/or publish in peer-reviewed journals. Keywords: Citizen science, Amphibians, Reptiles, Birds, Mammals

  5. [3H]Azidodantrolene photoaffinity labeling, synthetic domain peptides and monoclonal antibody reactivity identify the dantrolene binding sequence on RyR1

    Energy Technology Data Exchange (ETDEWEB)

    Paul-Pletzer, Kalanethee; Yamamoto, Takeshi; Bhat, Manju B.; Ma, Jianjie; Ikemoto, Noriaki; Jimenez, Leslie S.; Morimoto, Hiromi; Williams, Philip G.; Parness, Jerome

    2002-06-14

    Dantrolene is a drug that suppresses intracellular Ca2+ release from sarcoplasmic reticulum in normal skeletal muscle and is used as a therapeutic agent in individuals susceptible to malignant hyperthermia. Though its precise mechanism of action has not been elucidated, we have identified the N-terminal region (amino acids 1-1400) of the skeletal muscle isoform of the ryanodine receptor (RyR1), the primary Ca2+ release channel in sarcoplasmic reticulum, as a molecular target for dantrolene using the photoaffinity analog [3H]azidodantrolene(1). Here, we demonstrate that heterologously expressed RyR1 retains its capacity to be specifically labeled with [3H]azidodantrolene,indicating that muscle specific factors are not required for this ligand-receptor interaction. Synthetic domain peptides of RyR1, previously shown to affect RyR1 function in vitro and in vivo, were exploited as potential drug binding site mimics and used in photoaffinity labeling experiments. Only DP1 and DP1-2, peptide s containing the amino acid sequence corresponding to RyR1 residues 590-609, were specifically labeled by [3H]azidodantrolene. A monoclonal anti-RyR1 antibody which recognizes RyR1 and its 1400 amino acid N-terminal fragment, recognizes DP1 and DP1-2 in both Western blots and immunoprecipitation assays, and specifically inhibits [3H]azidodantrolene photolabeling of RyR1 and its N-terminal fragment in sarcoplasmic reticulum. Our results indicate that synthetic domain peptides can mimic a native, ligand binding conformation in vitro, and that the dantrolene binding site and the epitope for the monoclonal antibody on RyR1 are equivalent and composed of amino-acids 590-609.

  6. Where the wild things are: Predicting hotspots of seabird aggregations in the California Current System

    Science.gov (United States)

    Nur, N.; Jahncke, J.; Herzog, M.P.; Howar, J.; Hyrenbach, K.D.; Zamon, J.E.; Ainley, D.G.; Wiens, J.A.; Morgan, K.; Balance, L.T.; Stralberg, D.

    2011-01-01

    Marine Protected Areas (MPAs) provide an important tool for conservation of marine ecosystems. To be most effective, these areas should be strategically located in a manner that supports ecosystem function. To inform marine spatial planning and support strategic establishment of MPAs within the California Current System, we identified areas predicted to support multispecies aggregations of seabirds ("hotspot????). We developed habitat-association models for 16 species using information from at-sea observations collected over an 11-year period (1997-2008), bathymetric data, and remotely sensed oceanographic data for an area from north of Vancouver Island, Canada, to the USA/Mexico border and seaward 600 km from the coast. This approach enabled us to predict distribution and abundance of seabirds even in areas of few or no surveys. We developed single-species predictive models using a machine-learning algorithm: bagged decision trees. Single-species predictions were then combined to identify potential hotspots of seabird aggregation, using three criteria: (1) overall abundance among species, (2) importance of specific areas ("core area????) to individual species, and (3) predicted persistence of hotspots across years. Model predictions were applied to the entire California Current for four seasons (represented by February, May, July, and October) in each of 11 years. Overall, bathymetric variables were often important predictive variables, whereas oceanographic variables derived from remotely sensed data were generally less important. Predicted hotspots often aligned with currently protected areas (e.g., National Marine Sanctuaries), but we also identified potential hotspots in Northern California/Southern Oregon (from Cape Mendocino to Heceta Bank), Southern California (adjacent to the Channel Islands), and adjacent to Vancouver Island, British Columbia, that are not currently included in protected areas. Prioritization and identification of multispecies hotspots

  7. Computational Characterization of Small Molecules Binding to the Human XPF Active Site and Virtual Screening to Identify Potential New DNA Repair Inhibitors Targeting the ERCC1-XPF Endonuclease

    Directory of Open Access Journals (Sweden)

    Francesco Gentile

    2018-04-01

    Full Text Available The DNA excision repair protein ERCC-1-DNA repair endonuclease XPF (ERCC1-XPF is a heterodimeric endonuclease essential for the nucleotide excision repair (NER DNA repair pathway. Although its activity is required to maintain genome integrity in healthy cells, ERCC1-XPF can counteract the effect of DNA-damaging therapies such as platinum-based chemotherapy in cancer cells. Therefore, a promising approach to enhance the effect of these therapies is to combine their use with small molecules, which can inhibit the repair mechanisms in cancer cells. Currently, there are no structures available for the catalytic site of the human ERCC1-XPF, which performs the metal-mediated cleavage of a DNA damaged strand at 5′. We adopted a homology modeling strategy to build a structural model of the human XPF nuclease domain which contained the active site and to extract dominant conformations of the domain using molecular dynamics simulations followed by clustering of the trajectory. We investigated the binding modes of known small molecule inhibitors targeting the active site to build a pharmacophore model. We then performed a virtual screening of the ZINC Is Not Commercial 15 (ZINC15 database to identify new ERCC1-XPF endonuclease inhibitors. Our work provides structural insights regarding the binding mode of small molecules targeting the ERCC1-XPF active site that can be used to rationally optimize such compounds. We also propose a set of new potential DNA repair inhibitors to be considered for combination cancer therapy strategies.

  8. Meiotic recombination hotspots - a comparative view.

    Science.gov (United States)

    Choi, Kyuha; Henderson, Ian R

    2015-07-01

    During meiosis homologous chromosomes pair and undergo reciprocal genetic exchange, termed crossover. Meiotic recombination has a profound effect on patterns of genetic variation and is an important tool during crop breeding. Crossovers initiate from programmed DNA double-stranded breaks that are processed to form single-stranded DNA, which can invade a homologous chromosome. Strand invasion events mature into double Holliday junctions that can be resolved as crossovers. Extensive variation in the frequency of meiotic recombination occurs along chromosomes and is typically focused in narrow hotspots, observed both at the level of DNA breaks and final crossovers. We review methodologies to profile hotspots at different steps of the meiotic recombination pathway that have been used in different eukaryote species. We then discuss what these studies have revealed concerning specification of hotspot locations and activity and the contributions of both genetic and epigenetic factors. Understanding hotspots is important for interpreting patterns of genetic variation in populations and how eukaryotic genomes evolve. In addition, manipulation of hotspots will allow us to accelerate crop breeding, where meiotic recombination distributions can be limiting. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  9. Structure-guided approach identifies a novel class of HIV-1 ribonuclease H inhibitors: binding mode insights through magnesium complexation and site-directed mutagenesis studies

    DEFF Research Database (Denmark)

    Poongavanam, Vasanthanathan; Corona, Angela; Steinmann, Casper

    2018-01-01

    is a long and expensive process that can be speeded up by in silico methods. In the present study, a structure-guided screening is coupled with a similarity-based search on the Specs database to identify a new class of HIV-1 RNase H inhibitors. Out of the 45 compounds selected for experimental testing, 15...... inhibited the RNase H function below 100 μM with three hits exhibiting IC50 values active compound, AA, inhibits HIV-1 RNase H with an IC50 of 5.1 μM and exhibits a Mg-independent mode of inhibition. Site-directed mutagenesis studies provide valuable insight into the binding mode of newly...

  10. Multi-species comparative analysis of the equine ACE gene identifies a highly conserved potential transcription factor binding site in intron 16.

    Science.gov (United States)

    Hamilton, Natasha A; Tammen, Imke; Raadsma, Herman W

    2013-01-01

    Angiotensin converting enzyme (ACE) is essential for control of blood pressure. The human ACE gene contains an intronic Alu indel (I/D) polymorphism that has been associated with variation in serum enzyme levels, although the functional mechanism has not been identified. The polymorphism has also been associated with cardiovascular disease, type II diabetes, renal disease and elite athleticism. We have characterized the ACE gene in horses of breeds selected for differing physical abilities. The equine gene has a similar structure to that of all known mammalian ACE genes. Nine common single nucleotide polymorphisms (SNPs) discovered in pooled DNA were found to be inherited in nine haplotypes. Three of these SNPs were located in intron 16, homologous to that containing the Alu polymorphism in the human. A highly conserved 18 bp sequence, also within that intron, was identified as being a potential binding site for the transcription factors Oct-1, HFH-1 and HNF-3β, and lies within a larger area of higher than normal homology. This putative regulatory element may contribute to regulation of the documented inter-individual variation in human circulating enzyme levels, for which a functional mechanism is yet to be defined. Two equine SNPs occurred within the conserved area in intron 16, although neither of them disrupted the putative binding site. We propose a possible regulatory mechanism of the ACE gene in mammalian species which was previously unknown. This advance will allow further analysis leading to a better understanding of the mechanisms underpinning the associations seen between the human Alu polymorphism and enzyme levels, cardiovascular disease states and elite athleticism.

  11. Multi-species comparative analysis of the equine ACE gene identifies a highly conserved potential transcription factor binding site in intron 16.

    Directory of Open Access Journals (Sweden)

    Natasha A Hamilton

    Full Text Available Angiotensin converting enzyme (ACE is essential for control of blood pressure. The human ACE gene contains an intronic Alu indel (I/D polymorphism that has been associated with variation in serum enzyme levels, although the functional mechanism has not been identified. The polymorphism has also been associated with cardiovascular disease, type II diabetes, renal disease and elite athleticism. We have characterized the ACE gene in horses of breeds selected for differing physical abilities. The equine gene has a similar structure to that of all known mammalian ACE genes. Nine common single nucleotide polymorphisms (SNPs discovered in pooled DNA were found to be inherited in nine haplotypes. Three of these SNPs were located in intron 16, homologous to that containing the Alu polymorphism in the human. A highly conserved 18 bp sequence, also within that intron, was identified as being a potential binding site for the transcription factors Oct-1, HFH-1 and HNF-3β, and lies within a larger area of higher than normal homology. This putative regulatory element may contribute to regulation of the documented inter-individual variation in human circulating enzyme levels, for which a functional mechanism is yet to be defined. Two equine SNPs occurred within the conserved area in intron 16, although neither of them disrupted the putative binding site. We propose a possible regulatory mechanism of the ACE gene in mammalian species which was previously unknown. This advance will allow further analysis leading to a better understanding of the mechanisms underpinning the associations seen between the human Alu polymorphism and enzyme levels, cardiovascular disease states and elite athleticism.

  12. Collimation of extragalactic jets: evidence from hotspots

    International Nuclear Information System (INIS)

    Banhatti, D.G.

    1984-01-01

    A linear relation with slope near unity is found between the logarithms of the hotspot size perpendicular to the source major axis and the distance from the core for 14 compact and/ or intense hotspots selected from a sample of 31 quasars having the largest angular sizes at various redshifts, as observed at 4.87 GHz with sub-arcsec resolution. A slope significantly less than 1 implies that the jet feeding the hotspot is laterally confined by the intergalactic medium, whereas a slope of 1 does not distinguish between a laterally confined jet and a free jet. The relation is found to have a slope near 1 implying a 0deg.1 jet confined within a cone of half-angle 15deg to 20deg or a 1deg-wide free jet. (author)

  13. Consensus of sample-balanced classifiers for identifying ligand-binding residue by co-evolutionary physicochemical characteristics of amino acids

    KAUST Repository

    Chen, Peng

    2013-01-01

    Protein-ligand binding is an important mechanism for some proteins to perform their functions, and those binding sites are the residues of proteins that physically bind to ligands. So far, the state-of-the-art methods search for similar, known

  14. Carnivore hotspots in Peninsular Malaysia and their landscape attributes

    Science.gov (United States)

    van Manen, Frank T.

    2018-01-01

    Mammalian carnivores play a vital role in ecosystem functioning. However, they are prone to extinction because of low population densities and growth rates, and high levels of persecution or exploitation. In tropical biodiversity hotspots such as Peninsular Malaysia, rapid conversion of natural habitats threatens the persistence of this vulnerable group of animals. Here, we carried out the first comprehensive literature review on 31 carnivore species reported to occur in Peninsular Malaysia and updated their probable distribution. We georeferenced 375 observations of 28 species of carnivore from 89 unique geographic locations using records spanning 1948 to 2014. Using the Getis-Ord Gi*statistic and weighted survey records by IUCN Red List status, we identified hotspots of species that were of conservation concern and built regression models to identify environmental and anthropogenic landscape factors associated with Getis-Ord Gi* z scores. Our analyses identified two carnivore hotspots that were spatially concordant with two of the peninsula’s largest and most contiguous forest complexes, associated with Taman Negara National Park and Royal Belum State Park. A cold spot overlapped with the southwestern region of the Peninsula, reflecting the disappearance of carnivores with higher conservation rankings from increasingly fragmented natural habitats. Getis-Ord Gi* z scores were negatively associated with elevation, and positively associated with the proportion of natural land cover and distance from the capital city. Malaysia contains some of the world’s most diverse carnivore assemblages, but recent rates of forest loss are some of the highest in the world. Reducing poaching and maintaining large, contiguous tracts of lowland forests will be crucial, not only for the persistence of threatened carnivores, but for many mammalian species in general. PMID:29617402

  15. Carnivore hotspots in Peninsular Malaysia and their landscape attributes.

    Science.gov (United States)

    Ratnayeke, Shyamala; van Manen, Frank T; Clements, Gopalasamy Reuben; Kulaimi, Noor Azleen Mohd; Sharp, Stuart P

    2018-01-01

    Mammalian carnivores play a vital role in ecosystem functioning. However, they are prone to extinction because of low population densities and growth rates, and high levels of persecution or exploitation. In tropical biodiversity hotspots such as Peninsular Malaysia, rapid conversion of natural habitats threatens the persistence of this vulnerable group of animals. Here, we carried out the first comprehensive literature review on 31 carnivore species reported to occur in Peninsular Malaysia and updated their probable distribution. We georeferenced 375 observations of 28 species of carnivore from 89 unique geographic locations using records spanning 1948 to 2014. Using the Getis-Ord Gi*statistic and weighted survey records by IUCN Red List status, we identified hotspots of species that were of conservation concern and built regression models to identify environmental and anthropogenic landscape factors associated with Getis-Ord Gi* z scores. Our analyses identified two carnivore hotspots that were spatially concordant with two of the peninsula's largest and most contiguous forest complexes, associated with Taman Negara National Park and Royal Belum State Park. A cold spot overlapped with the southwestern region of the Peninsula, reflecting the disappearance of carnivores with higher conservation rankings from increasingly fragmented natural habitats. Getis-Ord Gi* z scores were negatively associated with elevation, and positively associated with the proportion of natural land cover and distance from the capital city. Malaysia contains some of the world's most diverse carnivore assemblages, but recent rates of forest loss are some of the highest in the world. Reducing poaching and maintaining large, contiguous tracts of lowland forests will be crucial, not only for the persistence of threatened carnivores, but for many mammalian species in general.

  16. Carnivore hotspots in Peninsular Malaysia and their landscape attributes

    Science.gov (United States)

    Ratnayeke, Shyamala; van Manen, Frank T.; Clements, Gopalasamy Reuben; Mohd Kulaimi, Noor Azleen; Sharp, Stuart P.

    2018-01-01

    Mammalian carnivores play a vital role in ecosystem functioning. However, they are prone to extinction because of low population densities and growth rates, and high levels of persecution or exploitation. In tropical biodiversity hotspots such as Peninsular Malaysia, rapid conversion of natural habitats threatens the persistence of this vulnerable group of animals. Here, we carried out the first comprehensive literature review on 31 carnivore species reported to occur in Peninsular Malaysia and updated their probable distribution. We georeferenced 375 observations of 28 species of carnivore from 89 unique geographic locations using records spanning 1948 to 2014. Using the Getis-Ord Gi*statistic and weighted survey records by IUCN Red List status, we identified hotspots of species that were of conservation concern and built regression models to identify environmental and anthropogenic landscape factors associated with Getis-Ord Gi* z scores. Our analyses identified two carnivore hotspots that were spatially concordant with two of the peninsula’s largest and most contiguous forest complexes, associated with Taman Negara National Park and Royal Belum State Park. A cold spot overlapped with the southwestern region of the Peninsula, reflecting the disappearance of carnivores with higher conservation rankings from increasingly fragmented natural habitats. Getis-Ord Gi* z scores were negatively associated with elevation, and positively associated with the proportion of natural land cover and distance from the capital city. Malaysia contains some of the world’s most diverse carnivore assemblages, but recent rates of forest loss are some of the highest in the world. Reducing poaching and maintaining large, contiguous tracts of lowland forests will be crucial, not only for the persistence of threatened carnivores, but for many mammalian species in general.

  17. Unique properties of multiple tandem copies of the M26 recombination hotspot in mitosis and meiosis in Schizosaccharomyces pombe.

    Science.gov (United States)

    Steiner, Walter W; Recor, Chelsea L; Zakrzewski, Bethany M

    2016-11-15

    The M26 hotspot of the fission yeast Schizosaccharomyces pombe is one of the best-characterized eukaryotic hotspots of recombination. The hotspot requires a seven bp sequence, ATGACGT, that serves as a binding site for the Atf1-Pcr1 transcription factor, which is also required for activity. The M26 hotspot is active in meiosis but not mitosis and is active in some but not all chromosomal contexts and not on a plasmid. A longer palindromic version of M26, ATGACGTCAT, shows significantly greater activity than the seven bp sequence. Here, we tested whether the properties of the seven bp sequence were also true of the longer sequence by placing one, two, or three copies of the sequence into the ade6 gene, where M26 was originally discovered. These constructs were tested for activity when located on a plasmid or on a chromosome in mitosis and meiosis. We found that two copies of the 10bp M26 motif on a chromosome were significantly more active for meiotic recombination than one, but no further increase was observed with three copies. However, three copies of M26 on a chromosome created an Atf1-dependent mitotic recombination hotspot. When located on a plasmid, M26 also appears to behave as a mitotic recombination hotspot; however, this behavior most likely results from Atf1-dependent inter-allelic complementation between the plasmid and chromosomal ade6 alleles. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. The prevalence of toxic hotspots in former Soviet countries

    International Nuclear Information System (INIS)

    Sharov, Petr; Dowling, Russell; Gogishvili, Megi; Jones, Barbara; Caravanos, Jack; McCartor, Andrew; Kashdan, Zachary; Fuller, Richard

    2016-01-01

    Using a global database of contaminated sites, toxic hotspots in eight former Soviet countries were analyzed to identify the prevalence, types and sources of toxic pollution, as well as their associated potential public health impacts. For this analysis, polluted sites in Armenia, Azerbaijan, Kazakhstan, Kyrgyzstan, Russia, Tajikistan, Ukraine, and Uzbekistan were compiled and analyzed. The levels of contamination of seven key pollutants were assessed in each country. 424 contaminated sites were identified using data from Blacksmith Institute. Pesticides, lead (Pb), radioactive metals, arsenic (As), mercury (Hg), chromium (Cr), and cadmium (Cd) were the most commonly identified key pollutants. Collectively, these sites pose health risks to an estimated 6.2 million residents. The existing data on toxic hotspots in former Soviet countries likely captures only a small percentage of actual contaminated sites, but suggests potentially severe public health consequences. Additional assessments are needed to understand the risks posed by toxic pollution in the region. - Highlights: • Pollution in 8 former Soviet countries poses a health risk to 6.2 million residents. • The most commonly found key pollutants are pesticides, lead, arsenic, and cadmium. • The majority of sites can be traced to Soviet legacy pollution. - 424 sites were identified in the analysis. Pesticides, Pb, radioactive metals, As, Hg, Cr, and Cd were the most common key pollutants, collectively affecting 6.2 million people.

  19. New Horizons-LEISA Observations Of Io's Hotspots During The 2007 Encounter

    Science.gov (United States)

    Tsang, Constantine; Rathbun, J. A.; Spencer, J. R.

    2012-10-01

    The New Horizons spacecraft flew past Jupiter and its satellites in February 2007. The flyby provided one of the most exquisite sets of observations of Io’s active plumes and hotspots yet taken, including many observations of a large 350 km high eruption plume at Tvashtar. Among the suite of instruments active during the flyby was the Linear Etalon Infrared Spectral Array (LEISA), a near-infrared imaging spectrometer. It covers the wavelength region between 1.25 and 2.5 µm, at a resolving power of 240, with a higher resolving power segment (R=540), covering 2.1 to 2.25 µm. Both segments share the same detector array to give on a 256 x 256 pixel spectral image at 62 µrad per pixel field-of-view. LEISA identified more than 30 individual hotspots on Io, over the seven spectral cubes taken during the flyby. We can measure the thermal emission from these volcanoes, and arrive at eruption temperatures by fitting blackbody curves to hotspot spectra. The temperatures of Tvashtar, Pele and East Girru were all derived in the Spencer et al., (2007) study. These volcanoes were consistent with basaltic volcanism with temperatures between 1287 and 1335 K. Here, we present blackbody fits of the other volcanic hotspots identified in the spectral images to complete the study of hotspot locations, eruption temperatures, emitting area and temporal variability where possible.

  20. Quantile-Based Permutation Thresholds for Quantitative Trait Loci Hotspots

    NARCIS (Netherlands)

    Neto, Elias Chaibub; Keller, Mark P.; Broman, Andrew F.; Attie, Alan D.; Jansen, Ritsert C.; Broman, Karl W.; Yandell, Brian S.; Borevitz, J.

    Quantitative trait loci (QTL) hotspots (genomic locations affecting many traits) are a common feature in genetical genomics studies and are biologically interesting since they may harbor critical regulators. Therefore, statistical procedures to assess the significance of hotspots are of key

  1. A novel type of peptidoglycan-binding domain highly specific for amidated D-Asp cross-bridge, identified in Lactobacillus casei bacteriophage endolysins.

    Science.gov (United States)

    Regulski, Krzysztof; Courtin, Pascal; Kulakauskas, Saulius; Chapot-Chartier, Marie-Pierre

    2013-07-12

    Peptidoglycan hydrolases (PGHs) are responsible for bacterial cell lysis. Most PGHs have a modular structure comprising a catalytic domain and a cell wall-binding domain (CWBD). PGHs of bacteriophage origin, called endolysins, are involved in bacterial lysis at the end of the infection cycle. We have characterized two endolysins, Lc-Lys and Lc-Lys-2, identified in prophages present in the genome of Lactobacillus casei BL23. These two enzymes have different catalytic domains but similar putative C-terminal CWBDs. By analyzing purified peptidoglycan (PG) degradation products, we showed that Lc-Lys is an N-acetylmuramoyl-L-alanine amidase, whereas Lc-Lys-2 is a γ-D-glutamyl-L-lysyl endopeptidase. Remarkably, both lysins were able to lyse only Gram-positive bacterial strains that possess PG with D-Ala(4)→D-Asx-L-Lys(3) in their cross-bridge, such as Lactococcus casei, Lactococcus lactis, and Enterococcus faecium. By testing a panel of L. lactis cell wall mutants, we observed that Lc-Lys and Lc-Lys-2 were not able to lyse mutants with a modified PG cross-bridge, constituting D-Ala(4)→L-Ala-(L-Ala/L-Ser)-L-Lys(3); moreover, they do not lyse the L. lactis mutant containing only the nonamidated D-Asp cross-bridge, i.e. D-Ala(4)→D-Asp-L-Lys(3). In contrast, Lc-Lys could lyse the ampicillin-resistant E. faecium mutant with 3→3 L-Lys(3)-D-Asn-L-Lys(3) bridges replacing the wild-type 4→3 D-Ala(4)-D-Asn-L-Lys(3) bridges. We showed that the C-terminal CWBD of Lc-Lys binds PG containing mainly D-Asn but not PG with only the nonamidated D-Asp-containing cross-bridge, indicating that the CWBD confers to Lc-Lys its narrow specificity. In conclusion, the CWBD characterized in this study is a novel type of PG-binding domain targeting specifically the D-Asn interpeptide bridge of PG.

  2. Hotspots of species richness, threat and endemism for terrestrial vertebrates in SW Europe

    Science.gov (United States)

    Pascual, López-López; Luigi, Maiorano; Alessandra, Falcucci; Emilio, Barba; Luigi, Boitani

    2011-09-01

    The Mediterranean basin, and the Iberian Peninsula in particular, represent an outstanding "hotspot" of biological diversity with a long history of integration between natural ecosystems and human activities. Using deductive distribution models, and considering both Spain and Portugal, we downscaled traditional range maps for terrestrial vertebrates (amphibians, breeding birds, mammals and reptiles) to the finest possible resolution with the data at hand, and we identified hotspots based on three criteria: i) species richness; ii) vulnerability, and iii) endemism. We also provided a first evaluation of the conservation status of biodiversity hotspots based on these three criteria considering both existing and proposed protected areas (i.e., Natura 2000). For the identification of hotspots, we used a method based on the cumulative distribution functions of species richness values. We found no clear surrogacy among the different types of hotspots in the Iberian Peninsula. The most important hotspots (considering all criteria) are located in the western and southwestern portions of the study area, in the Mediterranean biogeographical region. Existing protected areas are not specifically concentrated in areas of high species richness, with only 5.2% of the hotspots of total richness being currently protected. The Natura 2000 network can potentially constitute an important baseline for protecting vertebrate diversity in the Iberian Peninsula although further improvements are needed. We suggest taking a step forward in conservation planning in the Mediterranean basin, explicitly considering the history of the region as well as its present environmental context. This would allow moving from traditional reserve networks (conservation focused on "patterns") to considerations about the "processes" that generated present biodiversity.

  3. Automated hotspot analysis with aerial image CD metrology for advanced logic devices

    Science.gov (United States)

    Buttgereit, Ute; Trautzsch, Thomas; Kim, Min-ho; Seo, Jung-Uk; Yoon, Young-Keun; Han, Hak-Seung; Chung, Dong Hoon; Jeon, Chan-Uk; Meyers, Gary

    2014-09-01

    Continuously shrinking designs by further extension of 193nm technology lead to a much higher probability of hotspots especially for the manufacturing of advanced logic devices. The CD of these potential hotspots needs to be precisely controlled and measured on the mask. On top of that, the feature complexity increases due to high OPC load in the logic mask design which is an additional challenge for CD metrology. Therefore the hotspot measurements have been performed on WLCD from ZEISS, which provides the benefit of reduced complexity by measuring the CD in the aerial image and qualifying the printing relevant CD. This is especially of advantage for complex 2D feature measurements. Additionally, the data preparation for CD measurement becomes more critical due to the larger amount of CD measurements and the increasing feature diversity. For the data preparation this means to identify these hotspots and mark them automatically with the correct marker required to make the feature specific CD measurement successful. Currently available methods can address generic pattern but cannot deal with the pattern diversity of the hotspots. The paper will explore a method how to overcome those limitations and to enhance the time-to-result in the marking process dramatically. For the marking process the Synopsys WLCD Output Module was utilized, which is an interface between the CATS mask data prep software and the WLCD metrology tool. It translates the CATS marking directly into an executable WLCD measurement job including CD analysis. The paper will describe the utilized method and flow for the hotspot measurement. Additionally, the achieved results on hotspot measurements utilizing this method will be presented.

  4. Live hot, die young: transmission distortion in recombination hotspots.

    Directory of Open Access Journals (Sweden)

    Graham Coop

    2007-03-01

    Full Text Available There is strong evidence that hotspots of meiotic recombination in humans are transient features of the genome. For example, hotspot locations are not shared between human and chimpanzee. Biased gene conversion in favor of alleles that locally disrupt hotspots is a possible explanation of the short lifespan of hotspots. We investigate the implications of such a bias on human hotspots and their evolution. Our results demonstrate that gene conversion bias is a sufficiently strong force to produce the observed lack of sharing of intense hotspots between species, although sharing may be much more common for weaker hotspots. We investigate models of how hotspots arise, and find that only models in which hotspot alleles do not initially experience drive are consistent with observations of rather hot hotspots in the human genome. Mutations acting against drive cannot successfully introduce such hotspots into the population, even if there is direct selection for higher recombination rates, such as to ensure correct segregation during meiosis. We explore the impact of hotspot alleles on patterns of haplotype variation, and show that such alleles mask their presence in population genetic data, making them difficult to detect.

  5. Eliminating "Hotspots" in Digital Image Processing

    Science.gov (United States)

    Salomon, P. M.

    1984-01-01

    Signals from defective picture elements rejected. Image processing program for use with charge-coupled device (CCD) or other mosaic imager augmented with algorithm that compensates for common type of electronic defect. Algorithm prevents false interpretation of "hotspots". Used for robotics, image enhancement, image analysis and digital television.

  6. Forecasting Hotspots-A Predictive Analytics Approach.

    Science.gov (United States)

    Maciejewski, R; Hafen, R; Rudolph, S; Larew, S G; Mitchell, M A; Cleveland, W S; Ebert, D S

    2011-04-01

    Current visual analytics systems provide users with the means to explore trends in their data. Linked views and interactive displays provide insight into correlations among people, events, and places in space and time. Analysts search for events of interest through statistical tools linked to visual displays, drill down into the data, and form hypotheses based upon the available information. However, current systems stop short of predicting events. In spatiotemporal data, analysts are searching for regions of space and time with unusually high incidences of events (hotspots). In the cases where hotspots are found, analysts would like to predict how these regions may grow in order to plan resource allocation and preventative measures. Furthermore, analysts would also like to predict where future hotspots may occur. To facilitate such forecasting, we have created a predictive visual analytics toolkit that provides analysts with linked spatiotemporal and statistical analytic views. Our system models spatiotemporal events through the combination of kernel density estimation for event distribution and seasonal trend decomposition by loess smoothing for temporal predictions. We provide analysts with estimates of error in our modeling, along with spatial and temporal alerts to indicate the occurrence of statistically significant hotspots. Spatial data are distributed based on a modeling of previous event locations, thereby maintaining a temporal coherence with past events. Such tools allow analysts to perform real-time hypothesis testing, plan intervention strategies, and allocate resources to correspond to perceived threats.

  7. Hotspot Mainport Schiphol : midterm review report

    NARCIS (Netherlands)

    Döpp, S.; Brink, van den P.; Hartogensis, O.K.; Jacobs, A.; Homan, C.; Sondij, J.

    2012-01-01

    The focus of Knowledge for Climate (KfC) research in Hotspot Schiphol Mainport is to optimize the contribution of meteorological services to a sustainable operation and reliable operation of Schiphol airport. Three research projects have been carried out in the first tranche of the Knowledge for

  8. Artificial intelligence in neurodegenerative disease research: use of IBM Watson to identify additional RNA-binding proteins altered in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Bakkar, Nadine; Kovalik, Tina; Lorenzini, Ileana; Spangler, Scott; Lacoste, Alix; Sponaugle, Kyle; Ferrante, Philip; Argentinis, Elenee; Sattler, Rita; Bowser, Robert

    2018-02-01

    Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with no effective treatments. Numerous RNA-binding proteins (RBPs) have been shown to be altered in ALS, with mutations in 11 RBPs causing familial forms of the disease, and 6 more RBPs showing abnormal expression/distribution in ALS albeit without any known mutations. RBP dysregulation is widely accepted as a contributing factor in ALS pathobiology. There are at least 1542 RBPs in the human genome; therefore, other unidentified RBPs may also be linked to the pathogenesis of ALS. We used IBM Watson ® to sieve through all RBPs in the genome and identify new RBPs linked to ALS (ALS-RBPs). IBM Watson extracted features from published literature to create semantic similarities and identify new connections between entities of interest. IBM Watson analyzed all published abstracts of previously known ALS-RBPs, and applied that text-based knowledge to all RBPs in the genome, ranking them by semantic similarity to the known set. We then validated the Watson top-ten-ranked RBPs at the protein and RNA levels in tissues from ALS and non-neurological disease controls, as well as in patient-derived induced pluripotent stem cells. 5 RBPs previously unlinked to ALS, hnRNPU, Syncrip, RBMS3, Caprin-1 and NUPL2, showed significant alterations in ALS compared to controls. Overall, we successfully used IBM Watson to help identify additional RBPs altered in ALS, highlighting the use of artificial intelligence tools to accelerate scientific discovery in ALS and possibly other complex neurological disorders.

  9. Sequence- and interactome-based prediction of viral protein hotspots targeting host proteins: a case study for HIV Nef.

    Directory of Open Access Journals (Sweden)

    Mahdi Sarmady

    Full Text Available Virus proteins alter protein pathways of the host toward the synthesis of viral particles by breaking and making edges via binding to host proteins. In this study, we developed a computational approach to predict viral sequence hotspots for binding to host proteins based on sequences of viral and host proteins and literature-curated virus-host protein interactome data. We use a motif discovery algorithm repeatedly on collections of sequences of viral proteins and immediate binding partners of their host targets and choose only those motifs that are conserved on viral sequences and highly statistically enriched among binding partners of virus protein targeted host proteins. Our results match experimental data on binding sites of Nef to host proteins such as MAPK1, VAV1, LCK, HCK, HLA-A, CD4, FYN, and GNB2L1 with high statistical significance but is a poor predictor of Nef binding sites on highly flexible, hoop-like regions. Predicted hotspots recapture CD8 cell epitopes of HIV Nef highlighting their importance in modulating virus-host interactions. Host proteins potentially targeted or outcompeted by Nef appear crowding the T cell receptor, natural killer cell mediated cytotoxicity, and neurotrophin signaling pathways. Scanning of HIV Nef motifs on multiple alignments of hepatitis C protein NS5A produces results consistent with literature, indicating the potential value of the hotspot discovery in advancing our understanding of virus-host crosstalk.

  10. HOTSPOT Health Physics codes for the PC

    Energy Technology Data Exchange (ETDEWEB)

    Homann, S.G.

    1994-03-01

    The HOTSPOT Health Physics codes were created to provide Health Physics personnel with a fast, field-portable calculation tool for evaluating accidents involving radioactive materials. HOTSPOT codes are a first-order approximation of the radiation effects associated with the atmospheric release of radioactive materials. HOTSPOT programs are reasonably accurate for a timely initial assessment. More importantly, HOTSPOT codes produce a consistent output for the same input assumptions and minimize the probability of errors associated with reading a graph incorrectly or scaling a universal nomogram during an emergency. The HOTSPOT codes are designed for short-term (less than 24 hours) release durations. Users requiring radiological release consequences for release scenarios over a longer time period, e.g., annual windrose data, are directed to such long-term models as CAPP88-PC (Parks, 1992). Users requiring more sophisticated modeling capabilities, e.g., complex terrain; multi-location real-time wind field data; etc., are directed to such capabilities as the Department of Energy`s ARAC computer codes (Sullivan, 1993). Four general programs -- Plume, Explosion, Fire, and Resuspension -- calculate a downwind assessment following the release of radioactive material resulting from a continuous or puff release, explosive release, fuel fire, or an area contamination event. Other programs deal with the release of plutonium, uranium, and tritium to expedite an initial assessment of accidents involving nuclear weapons. Additional programs estimate the dose commitment from the inhalation of any one of the radionuclides listed in the database of radionuclides; calibrate a radiation survey instrument for ground-survey measurements; and screen plutonium uptake in the lung (see FIDLER Calibration and LUNG Screening sections).

  11. HOTSPOT Health Physics codes for the PC

    International Nuclear Information System (INIS)

    Homann, S.G.

    1994-03-01

    The HOTSPOT Health Physics codes were created to provide Health Physics personnel with a fast, field-portable calculation tool for evaluating accidents involving radioactive materials. HOTSPOT codes are a first-order approximation of the radiation effects associated with the atmospheric release of radioactive materials. HOTSPOT programs are reasonably accurate for a timely initial assessment. More importantly, HOTSPOT codes produce a consistent output for the same input assumptions and minimize the probability of errors associated with reading a graph incorrectly or scaling a universal nomogram during an emergency. The HOTSPOT codes are designed for short-term (less than 24 hours) release durations. Users requiring radiological release consequences for release scenarios over a longer time period, e.g., annual windrose data, are directed to such long-term models as CAPP88-PC (Parks, 1992). Users requiring more sophisticated modeling capabilities, e.g., complex terrain; multi-location real-time wind field data; etc., are directed to such capabilities as the Department of Energy's ARAC computer codes (Sullivan, 1993). Four general programs -- Plume, Explosion, Fire, and Resuspension -- calculate a downwind assessment following the release of radioactive material resulting from a continuous or puff release, explosive release, fuel fire, or an area contamination event. Other programs deal with the release of plutonium, uranium, and tritium to expedite an initial assessment of accidents involving nuclear weapons. Additional programs estimate the dose commitment from the inhalation of any one of the radionuclides listed in the database of radionuclides; calibrate a radiation survey instrument for ground-survey measurements; and screen plutonium uptake in the lung (see FIDLER Calibration and LUNG Screening sections)

  12. Development of a hotspot detector with an acrylic filter and dose rate survey meters

    International Nuclear Information System (INIS)

    Shirakawa, Yoshiyuki; Yamano, Toshiya; Kobayashi, Yusuke; Hara, Masaki

    2013-01-01

    Fukushima and adjacent regions still have a large number of high dose rate areas called hotspots. It is necessary to know these hotspots for efficient decontamination of radioactive substances such as 137 Cs and for relief of residents coming home. To find the hotspots rapidly, we have to specify the direction of the area where the dose rate is at least 1μSv/h higher than those of surroundings. We have developed a detector that consists of an acrylic filter and three NaI(Tl) scintillation survey meters, and the detector can be expected to indicate the direction of the hotspot in the short time. A basic performance of the detector was examined by using acrylic filters of 10, 15, 20 and 25cm diameter and a tiny sealed 137 Cs source of 3 MBq as the alternative of a hotspot. It demonstrated the possibility of identifying the direction of γ-rays emitted from the source in 90 seconds. (author)

  13. Climate-induced hotspots in surface energy fluxes from 1948 to 2000

    International Nuclear Information System (INIS)

    Sheng Li; Liu Shuhua; Liu Heping

    2010-01-01

    Understanding how land surfaces respond to climate change requires knowledge of land-surface processes, which control the degree to which interannual variability and mean trends in climatic variables affect the surface energy budget. We use the latest version of the Community Land Model version 3.5 (CLM3.5), which is driven by the latest updated hybrid reanalysis-observation atmospheric forcing dataset constructed by Princeton University, to obtain global distributions of the surface energy budget from 1948 to 2000. We identify climate change hotspots and surface energy flux hotspots from 1948 to 2000. Surface energy flux hotspots, which reflect regions with strong changes in surface energy fluxes, reveal seasonal variations with strong signals in winter, spring, and autumn and weak ones in summer. Locations for surface energy flux hotspots are not, however, fully linked with those for climate change hotspots, suggesting that only in some regions are land surfaces more responsive to climate change in terms of interannual variability and mean trends.

  14. Transmission of infectious diseases en route to habitat hotspots.

    Science.gov (United States)

    Benavides, Julio; Walsh, Peter D; Meyers, Lauren Ancel; Raymond, Michel; Caillaud, Damien

    2012-01-01

    The spread of infectious diseases in wildlife populations is influenced by patterns of between-host contacts. Habitat "hotspots"--places attracting a large numbers of individuals or social groups--can significantly alter contact patterns and, hence, disease propagation. Research on the importance of habitat hotspots in wildlife epidemiology has primarily focused on how inter-individual contacts occurring at the hotspot itself increase disease transmission. However, in territorial animals, epidemiologically important contacts may primarily occur as animals cross through territories of conspecifics en route to habitat hotspots. So far, the phenomenon has received little attention. Here, we investigate the importance of these contacts in the case where infectious individuals keep visiting the hotspots and in the case where these individuals are not able to travel to the hotspot any more. We developed a simulation epidemiological model to investigate both cases in a scenario when transmission at the hotspot does not occur. We find that (i) hotspots still exacerbate epidemics, (ii) when infectious individuals do not travel to the hotspot, the most vulnerable individuals are those residing at intermediate distances from the hotspot rather than nearby, and (iii) the epidemiological vulnerability of a population is the highest when the number of hotspots is intermediate. By altering animal movements in their vicinity, habitat hotspots can thus strongly increase the spread of infectious diseases, even when disease transmission does not occur at the hotspot itself. Interestingly, when animals only visit the nearest hotspot, creating additional artificial hotspots, rather than reducing their number, may be an efficient disease control measure.

  15. Preserving the evolutionary potential of floras in biodiversity hotspots.

    Science.gov (United States)

    Forest, Félix; Grenyer, Richard; Rouget, Mathieu; Davies, T Jonathan; Cowling, Richard M; Faith, Daniel P; Balmford, Andrew; Manning, John C; Procheş, Serban; van der Bank, Michelle; Reeves, Gail; Hedderson, Terry A J; Savolainen, Vincent

    2007-02-15

    One of the biggest challenges for conservation biology is to provide conservation planners with ways to prioritize effort. Much attention has been focused on biodiversity hotspots. However, the conservation of evolutionary process is now also acknowledged as a priority in the face of global change. Phylogenetic diversity (PD) is a biodiversity index that measures the length of evolutionary pathways that connect a given set of taxa. PD therefore identifies sets of taxa that maximize the accumulation of 'feature diversity'. Recent studies, however, concluded that taxon richness is a good surrogate for PD. Here we show taxon richness to be decoupled from PD, using a biome-wide phylogenetic analysis of the flora of an undisputed biodiversity hotspot--the Cape of South Africa. We demonstrate that this decoupling has real-world importance for conservation planning. Finally, using a database of medicinal and economic plant use, we demonstrate that PD protection is the best strategy for preserving feature diversity in the Cape. We should be able to use PD to identify those key regions that maximize future options, both for the continuing evolution of life on Earth and for the benefit of society.

  16. Seamounts are hotspots of pelagic biodiversity in the open ocean.

    Science.gov (United States)

    Morato, Telmo; Hoyle, Simon D; Allain, Valerie; Nicol, Simon J

    2010-05-25

    The identification of biodiversity hotspots and their management for conservation have been hypothesized as effective ways to protect many species. There has been a significant effort to identify and map these areas at a global scale, but the coarse resolution of most datasets masks the small-scale patterns associated with coastal habitats or seamounts. Here we used tuna longline observer data to investigate the role of seamounts in aggregating large pelagic biodiversity and to identify which pelagic species are associated with seamounts. Our analysis indicates that seamounts are hotspots of pelagic biodiversity. Higher species richness was detected in association with seamounts than with coastal or oceanic areas. Seamounts were found to have higher species diversity within 30-40 km of the summit, whereas for sets close to coastal habitat the diversity was lower and fairly constant with distance. Higher probability of capture and higher number of fish caught were detected for some shark, billfish, tuna, and other by-catch species. The study supports hypotheses that seamounts may be areas of special interest for management for marine pelagic predators.

  17. Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis

    Science.gov (United States)

    Malhotra, Deepti; Portales-Casamar, Elodie; Singh, Anju; Srivastava, Siddhartha; Arenillas, David; Happel, Christine; Shyr, Casper; Wakabayashi, Nobunao; Kensler, Thomas W.; Wasserman, Wyeth W.; Biswal, Shyam

    2010-01-01

    The Nrf2 (nuclear factor E2 p45-related factor 2) transcription factor responds to diverse oxidative and electrophilic environmental stresses by circumventing repression by Keap1, translocating to the nucleus, and activating cytoprotective genes. Nrf2 responses provide protection against chemical carcinogenesis, chronic inflammation, neurodegeneration, emphysema, asthma and sepsis in murine models. Nrf2 regulates the expression of a plethora of genes that detoxify oxidants and electrophiles and repair or remove damaged macromolecules, such as through proteasomal processing. However, many direct targets of Nrf2 remain undefined. Here, mouse embryonic fibroblasts (MEF) with either constitutive nuclear accumulation (Keap1−/−) or depletion (Nrf2−/−) of Nrf2 were utilized to perform chromatin-immunoprecipitation with parallel sequencing (ChIP-Seq) and global transcription profiling. This unique Nrf2 ChIP-Seq dataset is highly enriched for Nrf2-binding motifs. Integrating ChIP-Seq and microarray analyses, we identified 645 basal and 654 inducible direct targets of Nrf2, with 244 genes at the intersection. Modulated pathways in stress response and cell proliferation distinguish the inducible and basal programs. Results were confirmed in an in vivo stress model of cigarette smoke-exposed mice. This study reveals global circuitry of the Nrf2 stress response emphasizing Nrf2 as a central node in cell survival response. PMID:20460467

  18. Built environment analysis for road traffic hotspot locations in Moshi, Tanzania.

    Science.gov (United States)

    Waldon, Meredith; Ibingira, Treasure Joelson; de Andrade, Luciano; Mmbaga, Blandina T; Vissoci, João Ricardo N; Mvungi, Mark; Staton, Catherine A

    2018-02-08

    Road traffic injuries (RTIs) cause significant morbidity and mortality in low- and middle-income countries. Investigation of high risk areas for RTIs is needed to guide improvements. This study provides built environmental analysis of road traffic crash hotspots within Moshi, Tanzania. Spatial analysis of police data identified 36 hotspots. Qualitative comparative analysis revealed 40% of crash sites were on local roads without night lighting and increased motorcycle density. Paved narrow roads represented 26% of hotspots and 13% were unpaved roads with uneven roadsides. Roadside unevenness was more predominate in low risk [n = 19, (90.5%)] than high risk sites [n = 7 (46.7%)]. Both low [n = 6 (28.6%)] and high risk [n = 1 (6.7%)] sites had minimal signage. All sites had informal pedestrian pathways. Little variability between risk sites suggests hazardous conditions are widespread. Findings suggest improvement in municipal infrastructure, signage and enforcement is needed to reduce RTI burden.

  19. Structural and energetic hot-spots for the interaction between a ladder-like polycyclic ether and the anti-ciguatoxin antibody 10C9Fab.

    Science.gov (United States)

    Ui, Mihoko; Tanaka, Yoshikazu; Tsumuraya, Takeshi; Fujii, Ikuo; Inoue, Masayuki; Hirama, Masahiro; Tsumoto, Kouhei

    2011-03-01

    The mechanism by which anti-ciguatoxin antibody 10C9Fab recognizes a fragment of ciguatoxin CTX3C (CTX3C-ABCDE) was investigated by mutational analysis based on structural data. 10C9Fab has an extraordinarily large and deep antigen-binding pocket at the center of its variable region. We mutated several residues located at the antigen-binding pocket to Ala, and kinetic analysis of the interactions between the mutant proteins and the antigen fragment was performed. The results indicate that some residues associated with the rigid antigen-binding pocket are structural hot-spots and that L-N94 is an energetic hot-spot for association of the antibody with the antigen fragment CTX3C-ABCDE, suggesting the importance of structural complementarity and energetic hot-spot interactions for specific recognition of polycyclic ethers.

  20. Comparative phylogeography reveals deep lineages and regional evolutionary hotspots in the Mojave and Sonoran Deserts

    Science.gov (United States)

    Wood, Dustin A.; Vandergast, Amy G.; Barr, Kelly R.; Inman, Richard D.; Esque, Todd C.; Nussear, Kenneth E.; Fisher, Robert N.

    2013-01-01

    Aim: We explored lineage diversification within desert-dwelling fauna. Our goals were (1) to determine whether phylogenetic lineages and population expansions were consistent with younger Pleistocene climate fluctuation hypotheses or much older events predicted by pre-Pleistocene vicariance hypotheses, (2) to assess concordance in spatial patterns of genetic divergence and diversity among species and (3) to identify regional evolutionary hotspots of divergence and diversity and assess their conservation status. Location: Mojave, Colorado, and Sonoran Deserts, USA. Methods: We analysed previously published gene sequence data for twelve species. We used Bayesian gene tree methods to estimate lineages and divergence times. Within each lineage, we tested for population expansion and age of expansion using coalescent approaches. We mapped interpopulation genetic divergence and intra-population genetic diversity in a GIS to identify hotspots of highest genetic divergence and diversity and to assess whether protected lands overlapped with evolutionary hotspots. Results: In seven of the 12 species, lineage divergence substantially predated the Pleistocene. Historical population expansion was found in eight species, but expansion events postdated the Last Glacial Maximum (LGM) in only four. For all species assessed, six hotspots of high genetic divergence and diversity were concentrated in the Colorado Desert, along the Colorado River and in the Mojave/Sonoran ecotone. At least some proportion of the land within each recovered hotspot was categorized as protected, yet four of the six also overlapped with major areas of human development. Main conclusions: Most of the species studied here diversified into distinct Mojave and Sonoran lineages prior to the LGM – supporting older diversification hypotheses. Several evolutionary hotspots were recovered but are not strategically paired with areas of protected land. Long-term preservation of species-level biodiversity would

  1. Identification of burden hotspots and risk factors for cholera in India: An observational study.

    Science.gov (United States)

    Ali, Mohammad; Sen Gupta, Sanjukta; Arora, Nisha; Khasnobis, Pradeep; Venkatesh, Srinivas; Sur, Dipika; Nair, Gopinath B; Sack, David A; Ganguly, Nirmal K

    2017-01-01

    Even though cholera has existed for centuries and many parts of the country have sporadic, endemic and epidemic cholera, it is still an under-recognized health problem in India. A Cholera Expert Group in the country was established to gather evidence and to prepare a road map for control of cholera in India. This paper identifies cholera burden hotspots and factors associated with an increased risk of the disease. We acquired district level data on cholera case reports of 2010-2015 from the Integrated Disease Surveillance Program. Socioeconomic characteristics and coverage of water and sanitation was obtained from the 2011 census. Spatial analysis was performed to identify cholera hotspots, and a zero-inflated Poisson regression was employed to identify the factors associated with cholera and predicted case count in the district. 27,615 cholera cases were reported during the 6-year period. Twenty-four of 36 states of India reported cholera during these years, and 13 states were classified as endemic. Of 641 districts, 78 districts in 15 states were identified as "hotspots" based on the reported cases. On the other hand, 111 districts in nine states were identified as "hotspots" from model-based predicted number of cases. The risk for cholera in a district was negatively associated with the coverage of literate persons, households using treated water source and owning mobile telephone, and positively associated with the coverage of poor sanitation and drainage conditions and urbanization level in the district. The study reaffirms that cholera continues to occur throughout a large part of India and identifies the burden hotspots and risk factors. Policymakers may use the findings of the article to develop a roadmap for prevention and control of cholera in India.

  2. The emergence of motives in liminal hotspots

    DEFF Research Database (Denmark)

    Nissen, Morten; Sørensen, Kathrine Solgaard

    2017-01-01

    The concept of “motivation” commonly constructs as a psychological essence what is really the paradoxical imposition of a required desire. While the resulting impasse blocked theoretical development for around four decades, pragmatic motivational techniques evolved regardless. These could...... motivation–resistance contradiction; then through pragmatic approaches in counseling, i.e., the prevalent cognitive-client-centered form and the “solution-focused brief therapy” approach—and finally as motives emergent in liminal hotspots....

  3. SPITZER OBSERVATIONS OF HOTSPOTS IN RADIO LOBES

    International Nuclear Information System (INIS)

    Werner, Michael W.; Murphy, David W.; Livingston, John H.; Gorjian, Varoujan; Jones, Dayton L.; Meier, David L.; Lawrence, Charles R.

    2012-01-01

    We have carried out a systematic search with Spitzer Warm Mission and archival data for infrared emission from the hotspots in radio lobes that have been described by Hardcastle et al. These hotspots have been detected with both radio and X-ray observations, but an observation at an intermediate frequency in the infrared can be critical to distinguish between competing models for particle acceleration and radiation processes in these objects. Between the archival and warm mission data, we report detections of 18 hotspots; the archival data generally include detections at all four IRAC bands, the Warm Mission data only at 3.6 μm. Using a theoretical formalism adopted from Godfrey et al., we fit both archival and warm mission spectral energy distributions (SEDs)—including radio, X-ray, and optical data from Hardcastle as well as the Spitzer data—with a synchrotron self-Compton (SSC) model, in which the X-rays are produced by Compton scattering of the radio frequency photons by the energetic electrons which radiate them. With one exception, an SSC model requires that the magnetic field be less or much less than the equipartition value which minimizes total energy and has comparable amounts of energy in the magnetic field and in the energetic particles. This conclusion agrees with those of comparable recent studies of hotspots, and with the analysis presented by Hardcastle et al. We also show that the infrared data rule out the simplest synchrotron-only models for the SEDs. We briefly discuss the implications of these results and of alternate interpretations of the data.

  4. Forecasting hotspots using predictive visual analytics approach

    Science.gov (United States)

    Maciejewski, Ross; Hafen, Ryan; Rudolph, Stephen; Cleveland, William; Ebert, David

    2014-12-30

    A method for forecasting hotspots is provided. The method may include the steps of receiving input data at an input of the computational device, generating a temporal prediction based on the input data, generating a geospatial prediction based on the input data, and generating output data based on the time series and geospatial predictions. The output data may be configured to display at least one user interface at an output of the computational device.

  5. Can we detect oceanic biodiversity hotspots from space?

    Science.gov (United States)

    De Monte, Silvia; Soccodato, Alice; Alvain, Séverine; d'Ovidio, Francesco

    2013-10-01

    Understanding the variability of marine biodiversity is a central issue in microbiology. Current observational programs are based on in situ studies, but their implementation at the global scale is particularly challenging, owing to the ocean extent, its temporal variability and the heterogeneity of the data sources on which compilations are built. Here, we explore the possibility of identifying phytoplanktonic biodiversity hotspots from satellite. We define a Shannon entropy index based on patchiness in ocean color bio-optical anomalies. This index provides a high resolution (1 degree) global coverage. It shows a relation to temperature and mid-latitude maxima in accordance with those previously evidenced in microbiological biodiversity model and observational studies. Regional maxima are in remarkable agreement with several known biodiversity hotspots for plankton organisms and even for higher levels of the marine trophic chain, as well as with some in situ planktonic biodiversity estimates (from Atlantic Meridional Transect cruise). These results encourage to explore marine biodiversity with a coordinated effort of the molecular, ecological and remote sensing communities.

  6. Detecting biodiversity hotspots by species-area relationships: a case study of Mediterranean beetles.

    Science.gov (United States)

    Fattorini, Simone

    2006-08-01

    Any method of identifying hotspots should take into account the effect of area on species richness. I examined the importance of the species-area relationship in determining tenebrionid (Coleoptera: Tenebrionidae) hotspots on the Aegean Islands (Greece). Thirty-two islands and 170 taxa (species and subspecies) were included in this study. I tested several species-area relationship models with linear and nonlinear regressions, including power exponential, negative exponential, logistic, Gompertz, Weibull, Lomolino, and He-Legendre functions. Islands with positive residuals were identified as hotspots. I also analyzed the values of the C parameter of the power function and the simple species-area ratios. Species richness was significantly correlated with island area for all models. The power function model was the most convenient one. Most functions, however identified certain islands as hotspots. The importance of endemics in insular biotas should be evaluated carefully because they are of high conservation concern. The simple use of the species-area relationship can be problematic when areas with no endemics are included. Therefore the importance of endemics should be evaluated according to different methods, such as percentages, to take into account different levels of endemism and different kinds of "endemics" (e.g., endemic to single islands vs. endemic to the archipelago). Because the species-area relationship is a key pattern in ecology, my findings can be applied at broader scales.

  7. Cross-Neutralising Nanobodies Bind to a Conserved Pocket in the Hemagglutinin Stem Region Identified Using Yeast Display and Deep Mutational Scanning.

    Directory of Open Access Journals (Sweden)

    Tiziano Gaiotto

    Full Text Available Cross-neutralising monoclonal antibodies against influenza hemagglutinin (HA are of considerable interest as both therapeutics and diagnostic tools. We have recently described five different single domain antibodies (nanobodies which share this cross-neutralising activity and suggest their small size, high stability, and cleft binding properties may present distinct advantages over equivalent conventional antibodies. We have used yeast display in combination with deep mutational scanning to give residue level resolution of positions in the antibody-HA interface which are crucial for binding. In addition, we have mapped positions within HA predicted to have minimal effect on antibody binding when mutated. Our cross-neutralising nanobodies were shown to bind to a highly conserved pocket in the HA2 domain of A(H1N1pdm09 influenza virus overlapping with the fusion peptide suggesting their mechanism of action is through the inhibition of viral membrane fusion. We also note that the epitope overlaps with that of CR6261 and F10 which are human monoclonal antibodies in clinical development as immunotherapeutics. Although all five nanobodies mapped to the same highly conserved binding pocket we observed differences in the size of the epitope footprint which has implications in comparing the relative genetic barrier each nanobody presents to a rapidly evolving influenza virus. To further refine our epitope map, we have re-created naturally occurring mutations within this HA stem epitope and tested their effect on binding using yeast display. We have shown that a D46N mutation in the HA2 stem domain uniquely interferes with binding of R2b-E8. Further testing of this substitution in the context of full length purified HA from 1918 H1N1 pandemic (Spanish flu, 2009 H1N1 pandemic (swine flu and highly pathogenic avian influenza H5N1 demonstrated binding which correlated with D46 whereas binding to seasonal H1N1 strains carrying N46 was absent. In addition, our

  8. Threatened Plants in China’s Sanjiang Plain: Hotspot Distributions and Gap Analysis

    Directory of Open Access Journals (Sweden)

    Baojia Du

    2018-01-01

    Full Text Available Global biodiversity is markedly decreasing in response to climate change and human disturbance. Sanjiang Plain is recognized as a biodiversity hotspot in China due to its high forest and wetland coverage, but species are being lost at an unprecedented rate, induced by anthropogenic activities. Identifying hotspot distributions and conservation gaps of threatened species is of particular significance for enhancing the conservation of biodiversity. Specifically, we integrated the principles and methods of spatial hotspot inspection, geographic information system (GIS technology and spatial autocorrelation analysis along with fieldwork to determine the spatial distribution patterns and unprotected hotspots of vulnerable and endangered plants in Sanjiang Plain. A gap analysis of the conservation status of vulnerable and endangered plants was conducted. Our results indicate that six nationally-protected plants were not observed in nature reserves or were without any protection, while the protection rates were <10% for 10 other nationally-protected plants. Protected areas (PAs cover <5% of the distribution areas for 31 threatened plant species, while only five species are covered by national nature reserves (NNRs within >50% of the distribution areas. We found 30 hotspots with vulnerable and endangered plants in the study area, but the area covered by NNRs is very limited. Most of the hotspots were located in areas with a high-high aggregation of plant species. Therefore, it is necessary to expand the area of existing nature reserves, establish miniature protection plots and create new PAs and ecological corridors to link the existing PAs. Our findings can contribute to the design of a PA network for botanical conservation.

  9. Investigation of naphthofuran moiety as potential dual inhibitor against BACE-1 and GSK-3β: molecular dynamics simulations, binding energy, and network analysis to identify first-in-class dual inhibitors against Alzheimer's disease.

    Science.gov (United States)

    Kumar, Akhil; Srivastava, Gaurava; Srivastava, Swati; Verma, Seema; Negi, Arvind S; Sharma, Ashok

    2017-08-01

    BACE-1 and GSK-3β are potential therapeutic drug targets for Alzheimer's disease. Recently, both the targets received attention for designing dual inhibitors for Alzheimer's disease. Until now, only two-scaffold triazinone and curcumin have been reported as BACE-1 and GSK-3β dual inhibitors. Docking, molecular dynamics, clustering, binding energy, and network analysis of triazinone derivatives with BACE-1 and GSK-3β was performed to get molecular insight into the first reported dual inhibitor. Further, we designed and evaluated a naphthofuran series for its ability to inhibit BACE-1 and GSK-3β with the computational approaches. Docking study of naphthofuran series showed a good binding affinity towards both the targets. Molecular dynamics, binding energy, and network analysis were performed to compare their binding with the targets and amino acids responsible for binding. Naphthofuran series derivatives showed good interaction within the active site residues of both of the targets. Hydrogen bond occupancy and binding energy suggested strong binding with the targets. Dual-inhibitor binding was mostly governed by the hydrophobic interactions for both of the targets. Per residue energy decomposition and network analysis identified the key residues involved in the binding and inhibiting BACE-1 and GSK-3β. The results indicated that naphthofuran series derivative 11 may be a promising first-in-class dual inhibitor against BACE-1 and GSK-3β. This naphthofuran series may be further explored to design better dual inhibitors. Graphical abstract Naphthofuran derivative as a dual inhibitor for BACE-1 and GSK-3β.

  10. Overview of geopolitical hotspots : OPEC

    International Nuclear Information System (INIS)

    Cisneros-Lavaller, A.

    2004-01-01

    This presentation reviewed the recent history (from 1998) of export volumes and prices of OPEC, oil exporting countries. It summarized cyclical trends in OPEC's behaviour and claims that changes to the current Price Defense Strategy could occur by 2010. The presentation also outlined the production behaviour of different countries in compliance with OPEC agreements. Algeria, Iraq, Venezuela and Nigeria were identified as significant case studies for several reasons, including future production increases from those countries. Two divergent OPEC scenarios were presented, from re-accommodation to a free for all type of policy within the organizational context for the mid-term. The author claims that it is time to review OPEC long-term policy to ensure revenue maximization. A change in OPEC policy is viable because it is possible to achieve comparable revenue with a combination of larger production volumes and more moderate prices. tabs., figs

  11. HOTSPOT: The Snake River Scientifi c Drilling Project— Tracking the Yellowstone Hotspot Through Space and Time

    Directory of Open Access Journals (Sweden)

    Douglas F. Williams

    2006-09-01

    Full Text Available The project “HOTSPOT: Scientifi c Drilling of the Snake River Plain” held its inaugural workshop in Twin Falls, Idaho, U.S.A. on 18–21 May 2006. This inter-disciplinary workshop, sponsored by the International Continental Scientifi c Drilling Program (ICDP, explored the major scientifi c and logistical issues central to a transect of boreholes along the hotspot track and addressing the geochemical evolution of continental lithosphere in response to interaction with deepseated mantle hotspots or plumes. A series of four to six bore holes is envisioned, each about 1.5–2.0 km deep and located along the axis of the Snake River Plain. The holes will specific ally target the origin and evolution of hotspot-related volcanism in space and time. To accomplish scientific and logistical planning, sixty scientists from six countries attended the workshop.

  12. Effect of transmission intensity on hotspots and micro-epidemiology of malaria in sub-Saharan Africa.

    Science.gov (United States)

    Mogeni, Polycarp; Omedo, Irene; Nyundo, Christopher; Kamau, Alice; Noor, Abdisalan; Bejon, Philip

    2017-06-30

    Malaria transmission intensity is heterogeneous, complicating the implementation of malaria control interventions. We provide a description of the spatial micro-epidemiology of symptomatic malaria and asymptomatic parasitaemia in multiple sites. We assembled data from 19 studies conducted between 1996 and 2015 in seven countries of sub-Saharan Africa with homestead-level geospatial data. Data from each site were used to quantify spatial autocorrelation and examine the temporal stability of hotspots. Parameters from these analyses were examined to identify trends over varying transmission intensity. Significant hotspots of malaria transmission were observed in most years and sites. The risk ratios of malaria within hotspots were highest at low malaria positive fractions (MPFs) and decreased with increasing MPF (p hotspots was lowest at extremely low and extremely high MPFs, with a peak in statistical significance at an MPF of ~0.3. In four sites with longitudinal data we noted temporal instability and variable negative correlations between MPF and average age of symptomatic malaria across all sites, suggesting varying degrees of temporal stability. We observed geographical micro-variation in malaria transmission at sites with a variety of transmission intensities across sub-Saharan Africa. Hotspots are marked at lower transmission intensity, but it becomes difficult to show statistical significance when cases are sparse at very low transmission intensity. Given the predictability with which hotspots occur as transmission intensity falls, malaria control programmes should have a low threshold for responding to apparent clustering of cases.

  13. Computational analysis of phosphopeptide binding to the polo-box domain of the mitotic kinase PLK1 using molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    David J Huggins

    2010-08-01

    Full Text Available The Polo-Like Kinase 1 (PLK1 acts as a central regulator of mitosis and is over-expressed in a wide range of human tumours where high levels of expression correlate with a poor prognosis. PLK1 comprises two structural elements, a kinase domain and a polo-box domain (PBD. The PBD binds phosphorylated substrates to control substrate phosphorylation by the kinase domain. Although the PBD preferentially binds to phosphopeptides, it has a relatively broad sequence specificity in comparison with other phosphopeptide binding domains. We analysed the molecular determinants of recognition by performing molecular dynamics simulations of the PBD with one of its natural substrates, CDC25c. Predicted binding free energies were calculated using a molecular mechanics, Poisson-Boltzmann surface area approach. We calculated the per-residue contributions to the binding free energy change, showing that the phosphothreonine residue and the mainchain account for the vast majority of the interaction energy. This explains the very broad sequence specificity with respect to other sidechain residues. Finally, we considered the key role of bridging water molecules at the binding interface. We employed inhomogeneous fluid solvation theory to consider the free energy of water molecules on the protein surface with respect to bulk water molecules. Such an analysis highlights binding hotspots created by elimination of water molecules from hydrophobic surfaces. It also predicts that a number of water molecules are stabilized by the presence of the charged phosphate group, and that this will have a significant effect on the binding affinity. Our findings suggest a molecular rationale for the promiscuous binding of the PBD and highlight a role for bridging water molecules at the interface. We expect that this method of analysis will be very useful for probing other protein surfaces to identify binding hotspots for natural binding partners and small molecule inhibitors.

  14. The Crystal Structure of the Drosophila Germline Inducer Oskar Identifies Two Domains with Distinct Vasa Helicase- and RNA-Binding Activities

    Directory of Open Access Journals (Sweden)

    Mandy Jeske

    2015-07-01

    Full Text Available In many animals, the germ plasm segregates germline from soma during early development. Oskar protein is known for its ability to induce germ plasm formation and germ cells in Drosophila. However, the molecular basis of germ plasm formation remains unclear. Here, we show that Oskar is an RNA-binding protein in vivo, crosslinking to nanos, polar granule component, and germ cell-less mRNAs, each of which has a role in germline formation. Furthermore, we present high-resolution crystal structures of the two Oskar domains. RNA-binding maps in vitro to the C-terminal domain, which shows structural similarity to SGNH hydrolases. The highly conserved N-terminal LOTUS domain forms dimers and mediates Oskar interaction with the germline-specific RNA helicase Vasa in vitro. Our findings suggest a dual function of Oskar in RNA and Vasa binding, providing molecular clues to its germ plasm function.

  15. Detection of Tuberculosis Infection Hotspots Using Activity Spaces Based Spatial Approach in an Urban Tokyo, from 2003 to 2011.

    Directory of Open Access Journals (Sweden)

    Kiyohiko Izumi

    Full Text Available Identifying ongoing tuberculosis infection sites is crucial for breaking chains of transmission in tuberculosis-prevalent urban areas. Previous studies have pointed out that detection of local accumulation of tuberculosis patients based on their residential addresses may be limited by a lack of matching between residences and tuberculosis infection sites. This study aimed to identify possible tuberculosis hotspots using TB genotype clustering statuses and a concept of "activity space", a place where patients spend most of their waking hours. We further compared the spatial distribution by different residential statuses and describe urban environmental features of the detected hotspots.Culture-positive tuberculosis patients notified to Shinjuku city from 2003 to 2011 were enrolled in this case-based cross-sectional study, and their demographic and clinical information, TB genotype clustering statuses, and activity space were collected. Spatial statistics (Global Moran's I and Getis-Ord Gi* statistics identified significant hotspots in 152 census tracts, and urban environmental features and tuberculosis patients' characteristics in these hotspots were assessed.Of the enrolled 643 culture-positive tuberculosis patients, 416 (64.2% were general inhabitants, 42 (6.5% were foreign-born people, and 184 were homeless people (28.6%. The percentage of overall genotype clustering was 43.7%. Genotype-clustered general inhabitants and homeless people formed significant hotspots around a major railway station, whereas the non-clustered general inhabitants formed no hotspots. This suggested the detected hotspots of activity spaces may reflect ongoing tuberculosis transmission sites and were characterized by smaller residential floor size and a higher proportion of non-working households.Activity space-based spatial analysis suggested possible TB transmission sites around the major railway station and it can assist in further comprehension of TB transmission

  16. Detection of Tuberculosis Infection Hotspots Using Activity Spaces Based Spatial Approach in an Urban Tokyo, from 2003 to 2011.

    Science.gov (United States)

    Izumi, Kiyohiko; Ohkado, Akihiro; Uchimura, Kazuhiro; Murase, Yoshiro; Tatsumi, Yuriko; Kayebeta, Aya; Watanabe, Yu; Ishikawa, Nobukatsu

    2015-01-01

    Identifying ongoing tuberculosis infection sites is crucial for breaking chains of transmission in tuberculosis-prevalent urban areas. Previous studies have pointed out that detection of local accumulation of tuberculosis patients based on their residential addresses may be limited by a lack of matching between residences and tuberculosis infection sites. This study aimed to identify possible tuberculosis hotspots using TB genotype clustering statuses and a concept of "activity space", a place where patients spend most of their waking hours. We further compared the spatial distribution by different residential statuses and describe urban environmental features of the detected hotspots. Culture-positive tuberculosis patients notified to Shinjuku city from 2003 to 2011 were enrolled in this case-based cross-sectional study, and their demographic and clinical information, TB genotype clustering statuses, and activity space were collected. Spatial statistics (Global Moran's I and Getis-Ord Gi* statistics) identified significant hotspots in 152 census tracts, and urban environmental features and tuberculosis patients' characteristics in these hotspots were assessed. Of the enrolled 643 culture-positive tuberculosis patients, 416 (64.2%) were general inhabitants, 42 (6.5%) were foreign-born people, and 184 were homeless people (28.6%). The percentage of overall genotype clustering was 43.7%. Genotype-clustered general inhabitants and homeless people formed significant hotspots around a major railway station, whereas the non-clustered general inhabitants formed no hotspots. This suggested the detected hotspots of activity spaces may reflect ongoing tuberculosis transmission sites and were characterized by smaller residential floor size and a higher proportion of non-working households. Activity space-based spatial analysis suggested possible TB transmission sites around the major railway station and it can assist in further comprehension of TB transmission dynamics in an

  17. Identifying the functional part of heparin-binding protein (HBP) as a monocyte stimulator and the novel role of monocytes as HBP producers

    DEFF Research Database (Denmark)

    Schou, Morten; Djurup, René; Norris, Kjeld

    2011-01-01

    Heparin-binding protein (HBP), an evolutionary ancient and biologically highly important molecule in inflammation, is an inactive serine protease due to mutations in the catalytic triad. The histidine (position 41) in the conserved sequence TAAHC is mutated to serine and this sequence (TAASC) pla...

  18. Nanoscale hotspots due to nonequilibrium thermal transport

    International Nuclear Information System (INIS)

    Sinha, Sanjiv; Goodson, Kenneth E.

    2004-01-01

    Recent experimental and modeling efforts have been directed towards the issue of temperature localization and hotspot formation in the vicinity of nanoscale heat generating devices. The nonequilibrium transport conditions which develop around these nanoscale devices results in elevated temperatures near the heat source which can not be predicted by continuum diffusion theory. Efforts to determine the severity of this temperature localization phenomena in silicon devices near and above room temperature are of technological importance to the development of microelectronics and other nanotechnologies. In this work, we have developed a new modeling tool in order to explore the magnitude of the additional thermal resistance which forms around nanoscale hotspots from temperatures of 100-1000K. The models are based on a two fluid approximation in which thermal energy is transferred between ''stationary'' optical phonons and fast propagating acoustic phonon modes. The results of the model have shown excellent agreement with experimental results of localized hotspots in silicon at lower temperatures. The model predicts that the effect of added thermal resistance due to the nonequilibrium phonon distribution is greatest at lower temperatures, but is maintained out to temperatures of 1000K. The resistance predicted by the numerical code can be easily integrated with continuum models in order to predict the temperature distribution around nanoscale heat sources with improved accuracy. Additional research efforts also focused on the measurements of the thermal resistance of silicon thin films at higher temperatures, with a focus on polycrystalline silicon. This work was intended to provide much needed experimental data on the thermal transport properties for micro and nanoscale devices built with this material. Initial experiments have shown that the exposure of polycrystalline silicon to high temperatures may induce recrystallization and radically increase the thermal

  19. [Identification of anopheles breeding sites in the residual foci of low malaria transmission «hotspots» in Central and Western Senegal].

    Science.gov (United States)

    Sy, O; Konaté, L; Ndiaye, A; Dia, I; Diallo, A; Taïrou, F; Bâ, E L; Gomis, J F; Ndiaye, J L; Cissé, B; Gaye, O; Faye, O

    2016-02-01

    Malaria incidence has markedly declined in the Mbour, Fatick, Niakhar and Bambey districts (central and western Senegal) thanks to a scaling up of effective control measures namely LLINs (Long Lasting Insecticide Treated Net), ACTs (Artesunate Combination Therapy) and promoting care seeking. However malaria cases are now maintained by foci of transmission called hotspots. We evaluate the role of anopheles breeding sites in the identification of malaria hotspots in the health districts of Mbour, Fatick, Niakhar and Bambey. Surveys of breeding sites were made in 6 hotspot villages and 4 non-hotspot villages. A sample was taken in each water point with mosquito larvae by dipping method and the collected specimens were identified to the genus level. Additional parameters as name of the village and breeding sites, type of collection, original water turbidity, presence of vegetation, proximity to dwellings, geographic coordinates, sizes were also collected. Sixty-two water collections were surveyed and monitored between 2013 and 2014. Temporary natural breeding sites were predominant regardless of the epidemiological status of the village. Among the 31 breeding sites located within 500 meters of dwellings in hotspots villages, 70% carried Anopheles larvae during the rainy season while 43% of the 21 breeding sites located at similar distances in non-hotspot villages carried Anopheles larvae during the same period (P = 0.042). At the end of the rainy season, the trend is the same with 27% of positive breeding sites in hotspots and 14% in non-hotspots villages. The breeding sites encountered in hotspots villages are mostly small to medium size and are more productive by Anopheles larvae than those found in non-hotspot area. This study showed that the high frequency of smallest and productive breeding sites around and inside the villages can create conditions of residual transmission.

  20. A micro-epidemiological analysis of febrile malaria in Coastal Kenya showing hotspots within hotspots

    NARCIS (Netherlands)

    Bejon, P.; Williams, T.N.; Nyundo, C.; Hay, S.I.; Benz, D.; Gething, P.W.; Otiende, M.; Peshu, J.; Bashraheil, M.; Greenhouse, B.; Bousema, T.; Bauni, E.; Marsh, K.; Smith, D.L.; Borrmann, S.

    2014-01-01

    Malaria transmission is spatially heterogeneous. This reduces the efficacy of control strategies, but focusing control strategies on clusters or 'hotspots' of transmission may be highly effective. Among 1500 homesteads in coastal Kenya we calculated (a) the fraction of febrile children with positive

  1. Improved detection of coastal acid sulfate soil hotspots through biomonitoring of metal(loid) accumulation in water lilies (Nymphaea capensis).

    Science.gov (United States)

    Stroud, Jacqueline L; Collins, Richard N

    2014-07-15

    Anthropogenically disturbed coastal acid sulfate soils along the east coast of Australia, and worldwide, periodically result in the discharge of acid waters containing high concentrations of metals. Identifying priority sites (hotspots) within a catchment for acid sulfate soil remediation activities typically involves long-term monitoring of drainwater chemistry, including the capture of data on unpredictable rain-induced groundwater discharge events. To improve upon this monitoring approach, this study investigated using the water lily (Nymphaea capensis) as a biomonitor of drainage waters to identify hotspots in three acid sulfate soil impacted catchments (83 km(2)) in north-eastern New South Wales, Australia. In one catchment where the location of hotspots was known, water lily lamina concentrations of a suite of metal(loid)s were significantly (photspots revealed within catchment variation of plant metal concentrations up to 70-fold. High resolution maps produced from these results, therefore, provided strong evidence for the location of potential hotspots which were confirmed with measurements of drainwater chemistry during rain-induced groundwater discharge events. Median catchment lily accumulation was ca. 160 mg Al kg(-1) and 1,300 mg Fe kg(-1), with hotspots containing up to 6- and 10-fold higher Al and Fe concentrations. These findings suggest that biomonitoring with N. capensis can be an important tool to rapidly identify priority sites for remediation in acid sulfate soil impacted landscapes. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Rapid experimental SAD phasing and hot-spot identification with halogenated fragments

    Directory of Open Access Journals (Sweden)

    Joseph D. Bauman

    2016-01-01

    Full Text Available Through X-ray crystallographic fragment screening, 4-bromopyrazole was discovered to be a `magic bullet' that is capable of binding at many of the ligand `hot spots' found in HIV-1 reverse transcriptase (RT. The binding locations can be in pockets that are `hidden' in the unliganded crystal form, allowing rapid identification of these sites for in silico screening. In addition to hot-spot identification, this ubiquitous yet specific binding provides an avenue for X-ray crystallographic phase determination, which can be a significant bottleneck in the determination of the structures of novel proteins. The anomalous signal from 4-bromopyrazole or 4-iodopyrazole was sufficient to determine the structures of three proteins (HIV-1 RT, influenza A endonuclease and proteinase K by single-wavelength anomalous dispersion (SAD from single crystals. Both compounds are inexpensive, readily available, safe and very soluble in DMSO or water, allowing efficient soaking into crystals.

  3. Drosophila duplication hotspots are associated with late-replicating regions of the genome.

    Directory of Open Access Journals (Sweden)

    Margarida Cardoso-Moreira

    2011-11-01

    Full Text Available Duplications play a significant role in both extremes of the phenotypic spectrum of newly arising mutations: they can have severe deleterious effects (e.g. duplications underlie a variety of diseases but can also be highly advantageous. The phenotypic potential of newly arisen duplications has stimulated wide interest in both the mutational and selective processes shaping these variants in the genome. Here we take advantage of the Drosophila simulans-Drosophila melanogaster genetic system to further our understanding of both processes. Regarding mutational processes, the study of two closely related species allows investigation of the potential existence of shared duplication hotspots, and the similarities and differences between the two genomes can be used to dissect its underlying causes. Regarding selection, the difference in the effective population size between the two species can be leveraged to ask questions about the strength of selection acting on different classes of duplications. In this study, we conducted a survey of duplication polymorphisms in 14 different lines of D. simulans using tiling microarrays and combined it with an analogous survey for the D. melanogaster genome. By integrating the two datasets, we identified duplication hotspots conserved between the two species. However, unlike the duplication hotspots identified in mammalian genomes, Drosophila duplication hotspots are not associated with sequences of high sequence identity capable of mediating non-allelic homologous recombination. Instead, Drosophila duplication hotspots are associated with late-replicating regions of the genome, suggesting a link between DNA replication and duplication rates. We also found evidence supporting a higher effectiveness of selection on duplications in D. simulans than in D. melanogaster. This is also true for duplications segregating at high frequency, where we find evidence in D. simulans that a sizeable fraction of these mutations is

  4. Comparative analysis of Dendrobium plastomes and utility of plastomic mutational hotspots.

    Science.gov (United States)

    Zhitao, Niu; Shuying, Zhu; Jiajia, Pan; Ludan, Li; Jing, Sun; Xiaoyu, Ding

    2017-05-18

    Dendrobium is one of the largest genera in Orchidaceae, comprising about 800-1500 species mainly distributed in tropical Asia, Australasia, and Australia. There are 74 species and two varieties of this genus in China. Because of their ornamental and commercial value, Dendrobium orchids have been studied at low taxonomic levels. However, structural changes and effective mutational hotspots of Dendrobium plastomes have rarely been documented. Here, 30 Dendrobium plastomes were compared, comprising 25 newly sequenced in this study and five previously published. Except for their differences in NDH genes, these plastomes shared identical gene content and order. Comparative analyses revealed that the variation in size of Dendroubium plastomes was associated with dramatically changed length of InDels. Furthermore, ten loci were identified as the top-ten mutational hotspots, whose sequence variability was almost unchanged with more than 10 plastomes sampled, suggesting that they may be powerful markers for Dendrobium species. In addition, primer pairs of 47 polymorphic microsatellites were developed. After assessing the mean BS values of all combinations derived from the top-ten hotspots, we recommend that the combination of five hotspots-trnT-trnL, rpl32-trnL, clpP-psbB, trnL intron, and rps16-trnQ-should be used in the phylogenetic and identification studies of Dendrobium.

  5. Ocean-wide tracking of pelagic sharks reveals extent of overlap with longline fishing hotspots.

    Science.gov (United States)

    Queiroz, Nuno; Humphries, Nicolas E; Mucientes, Gonzalo; Hammerschlag, Neil; Lima, Fernando P; Scales, Kylie L; Miller, Peter I; Sousa, Lara L; Seabra, Rui; Sims, David W

    2016-02-09

    Overfishing is arguably the greatest ecological threat facing the oceans, yet catches of many highly migratory fishes including oceanic sharks remain largely unregulated with poor monitoring and data reporting. Oceanic shark conservation is hampered by basic knowledge gaps about where sharks aggregate across population ranges and precisely where they overlap with fishers. Using satellite tracking data from six shark species across the North Atlantic, we show that pelagic sharks occupy predictable habitat hotspots of high space use. Movement modeling showed sharks preferred habitats characterized by strong sea surface-temperature gradients (fronts) over other available habitats. However, simultaneous Global Positioning System (GPS) tracking of the entire Spanish and Portuguese longline-vessel fishing fleets show an 80% overlap of fished areas with hotspots, potentially increasing shark susceptibility to fishing exploitation. Regions of high overlap between oceanic tagged sharks and longliners included the North Atlantic Current/Labrador Current convergence zone and the Mid-Atlantic Ridge southwest of the Azores. In these main regions, and subareas within them, shark/vessel co-occurrence was spatially and temporally persistent between years, highlighting how broadly the fishing exploitation efficiently "tracks" oceanic sharks within their space-use hotspots year-round. Given this intense focus of longliners on shark hotspots, our study argues the need for international catch limits for pelagic sharks and identifies a future role of combining fine-scale fish and vessel telemetry to inform the ocean-scale management of fisheries.

  6. Lagrangian Hotspots of In-Use NOX Emissions from Transit Buses.

    Science.gov (United States)

    Kotz, Andrew J; Kittelson, David B; Northrop, William F

    2016-06-07

    In-use, spatiotemporal NOX emissions were measured from a conventional powertrain transit bus and a series electric hybrid bus over gradients of route kinetic intensity and ambient temperature. This paper introduces a new method for identifying NOX emissions hotspots along a bus route using high fidelity Lagrangian vehicle data to explore spatial interactions that may influence emissions production. Our study shows that the studied transit buses emit higher than regulated emissions because on-route operation does not accurately represent the range of engine operation tested according to regulatory standards. Using the Lagrangian hotspot detection, we demonstrate that NOX hotspots occurred at bus stops, during cold starts, on inclines, and for accelerations. On the selected routes, bus stops resulted in 3.3 times the route averaged emissions factor in grams/km without significant dependence on bus type or climate. The buses also emitted 2.3 times the route averaged NOX emissions factor at the beginning of each route due to cold selective catalytic reduction aftertreatment temperature. The Lagrangian hotspot detection technique demonstrated here could be employed in future connected vehicles empowered by advances in computational power, data storage capability, and improved sensor technology to optimize emissions as a function of spatial location.

  7. A Global Moving Hotspot Reference Frame: How well it fits?

    Science.gov (United States)

    Doubrovine, P. V.; Steinberger, B.; Torsvik, T. H.

    2010-12-01

    Since the early 1970s, when Jason Morgan proposed that hotspot tracks record motion of lithosphere over deep-seated mantle plumes, the concept of fixed hotspots has dominated the way we think about absolute plate reconstructions. In the last decade, with compelling evidence for southward drift of the Hawaiian hotspot from paleomagnetic studies, and for the relative motion between the Pacific and Indo-Atlantic hotspots from refined plate circuit reconstructions, the perception changed and a global moving hotspot reference frame (GMHRF) was introduced, in which numerical models of mantle convection and advection of plume conduits in the mantle flow were used to estimate hotspot motion. This reference frame showed qualitatively better performance in fitting hotspot tracks globally, but the error analysis and formal estimates of the goodness of fitted rotations were lacking in this model. Here we present a new generation of the GMHRF, in which updated plate circuit reconstructions and radiometric age data from the hotspot tracks were combined with numerical models of plume motion, and uncertainties of absolute plate rotations were estimated through spherical regression analysis. The overall quality of fit was evaluated using a formal statistical test, by comparing misfits produced by the model with uncertainties assigned to the data. Alternative plate circuit models linking the Pacific plate to the plates of Indo-Atlantic hemisphere were tested and compared to the fixed hotspot models with identical error budgets. Our results show that, with an appropriate choice of the Pacific plate circuit, it is possible to reconcile relative plate motions and modeled motions of mantle plumes globally back to Late Cretaceous time (80 Ma). In contrast, all fixed hotspot models failed to produce acceptable fits for Paleogene to Late Cretaceous time (30-80 Ma), highlighting significance of relative motion between the Pacific and Indo-Atlantic hotspots during this interval. The

  8. Development of Plate Reader and On-Line Microfluidic Screening to Identify Ligands of the 5-Hydroxytryptamine Binding Protein in Venoms

    Directory of Open Access Journals (Sweden)

    Reka A. Otvos

    2015-06-01

    Full Text Available The 5-HT3 receptor is a ligand-gated ion channel, which is expressed in the nervous system. Its antagonists are used clinically for treatment of postoperative- and radiotherapy-induced emesis and irritable bowel syndrome. In order to better understand the structure and function of the 5-HT3 receptor, and to allow for compound screening at this receptor, recently a serotonin binding protein (5HTBP was engineered with the Acetylcholine Binding Protein as template. In this study, a fluorescence enhancement assay for 5HTBP ligands was developed in plate-reader format and subsequently used in an on-line microfluidic format. Both assay types were validated using an existing radioligand binding assay. The on-line microfluidic assay was coupled to HPLC via a post-column split which allowed parallel coupling to a mass spectrometer to collect MS data. This high-resolution screening (HRS system is well suitable for compound mixture analysis. As a proof of principle, the venoms of Dendroapsis polylepis, Pseudonaja affinis and Pseudonaja inframacula snakes were screened and the accurate masses of the found bioactives were established. To demonstrate the subsequent workflow towards structural identification of bioactive proteins and peptides, the partial amino acid sequence of one of the bioactives from the Pseudonaja affinis venom was determined using a bottom-up proteomics approach.

  9. The problems with multi-species conservation: do hotspots, ideal ...

    African Journals Online (AJOL)

    South Africa urgently requires a national strategic plan for the conservation of the country's biodiversity. The for- mulation of such a plan would be relatively easy if centres (hotspots) of richness, endemism and rarity were con- gruent, both within and among many different taxa, if these hotspots captured a large proportion of ...

  10. The problems with multi-species conservation: do hotspots, ideal ...

    African Journals Online (AJOL)

    South Africa urgently requires a national strategic plan for the conservation of the country's biodiversity. The formulation of such a plan would be relatively easy if centres (hotspots) of richness, endemism and rarity were congruent, both within and among many different taxa, if these hotspots captured a large proportion of the ...

  11. Photothermal probing of plasmonic hotspots with nanomechanical resonator

    DEFF Research Database (Denmark)

    Schmid, Silvan; Wu, Kaiyu; Rindzevicius, Tomas

    2014-01-01

    Plasmonic nanostructures (hotspots) are key components e.g. in plasmon-enhanced spectroscopy, plasmonic solar cells, or as nano heat sources. The characterization of single hotspots is still challenging due to a lack of experimental tools. We present the direct photothermal probing and mapping...

  12. Hotspot relaxation dynamics in a current-carrying superconductor

    Science.gov (United States)

    Marsili, F.; Stevens, M. J.; Kozorezov, A.; Verma, V. B.; Lambert, Colin; Stern, J. A.; Horansky, R. D.; Dyer, S.; Duff, S.; Pappas, D. P.; Lita, A. E.; Shaw, M. D.; Mirin, R. P.; Nam, S. W.

    2016-03-01

    We experimentally studied the dynamics of optically excited hotspots in current-carrying WSi superconducting nanowires as a function of bias current, bath temperature, and excitation wavelength. We observed that the hotspot relaxation time depends on bias current, temperature, and wavelength. We explained this effect with a model based on quasiparticle recombination, which provides insight into the quasiparticle dynamics of superconductors.

  13. Hotspot Motion, Before and After the Hawaiian-Emperor Bend

    Science.gov (United States)

    Tarduno, J. A.; Bono, R. K.

    2014-12-01

    Hawaiian hotspot motion of >40 mm/yr is best documented by paleomagnetic investigations of basalt cores recovered by ocean drilling of the Emperor seamounts during ODP Leg 197 (Tarduno et al., 2003). These data indicate that the trend of the Emperor Seamounts dominantly records motion of the hotspot in the mantle, further suggesting that the great Hawaiian-Emperor bend (HEB) reflects mainly a change in hotspot motion. Data used for Pacific "absolute plate motion models" for times before the age of the HEB are also internally inconsistent with a fixed hotspot assumption; at present the best way to estimate Pacific absolute plate motion prior to the HEB bend is through use of predictions derived from plate circuits (e.g. Doubrovine and Tarduno, 2008). These analyses predict much less motion for the hotspot responsible for the Louisville Seamount chain, as has been observed by paleomagnetic analyses of cores recovered by IODP Expedition 330 (Koppers et al., 2012). Together, the ocean drilling data sets favor hotspot-specific processes to explain high drift rates, such as the model whereby the Hawaiian mantle plume was captured by a ridge in the Late Cretaceous, and subsequent changes in sub-Pacific mantle flow resulted in the trend of the Emperor Seamounts (Tarduno et al., 2009). However, the question of whether there is a smaller signal of motion between groups of hotspots remains. Plate circuit analyses yield a small discrepancy between predicted and actual hotspot locations for times between ca. 47 Ma and 10 Ma that could be a signal of continued southward migration of the Hawaiian hotspot. Alternatively, this could reflect the motion of the group of Indo-Atlantic hotspots relative to Hawaii. New paleomagnetic data from Midway Atoll (ca. 27 Ma) suggests little difference with the present-day latitude of the plume, indicating that the rate of motion of either the Hawaiian hotspot, or the Indo-Atlantic hotspot group, was about 15 mm/yr between 47 and 27 Ma. This

  14. Population growth, human development, and deforestation in biodiversity hotspots.

    Science.gov (United States)

    Jha, S; Bawa, K S

    2006-06-01

    Human population and development activities affect the rate of deforestation in biodiversity hotspots. We quantified the effect of human population growth and development on rates of deforestation and analyzed the relationship between these causal factors in the 1980s and 1990s. We compared the averages of population growth, human development index (HDI, which measures income, health, and education), and deforestation rate and computed correlations among these variables for countries that contain biodiversity hotspots. When population growth was high and HDI was low there was a high rate of deforestation, but when HDI was high, rate of deforestation was low, despite high population growth. The correlation among variables was significant for the 1990s but not for the 1980s. The relationship between population growth and HDI had a regional pattern that reflected the historical process of development. Based on the changes in HDI and deforestation rate over time, we identified two drivers of deforestation: policy choice and human-development constraints. Policy choices that disregard conservation may cause the loss of forests even in countries that are relatively developed. Lack of development in other countries, on the other hand, may increase the pressure on forests to meet the basic needs of the human population. Deforestation resulting from policy choices may be easier to fix than deforestation arising from human development constraints. To prevent deforestation in the countries that have such constraints, transfer of material and intellectual resources from developed countries may be needed. Popular interest in sustainable development in developed countries can facilitate the transfer of these resources.

  15. Hotspots, Lifelines, and the Safrr Haywired Earthquake Sequence

    Science.gov (United States)

    Ratliff, J. L.; Porter, K.

    2014-12-01

    Though California has experienced many large earthquakes (San Francisco, 1906; Loma Prieta, 1989; Northridge, 1994), the San Francisco Bay Area has not had a damaging earthquake for 25 years. Earthquake risk and surging reliance on smartphones and the Internet to handle everyday tasks raise the question: is an increasingly technology-reliant Bay Area prepared for potential infrastructure impacts caused by a major earthquake? How will a major earthquake on the Hayward Fault affect lifelines (roads, power, water, communication, etc.)? The U.S. Geological Survey Science Application for Risk Reduction (SAFRR) program's Haywired disaster scenario, a hypothetical two-year earthquake sequence triggered by a M7.05 mainshock on the Hayward Fault, addresses these and other questions. We explore four geographic aspects of lifeline damage from earthquakes: (1) geographic lifeline concentrations, (2) areas where lifelines pass through high shaking or potential ground-failure zones, (3) areas with diminished lifeline service demand due to severe building damage, and (4) areas with increased lifeline service demand due to displaced residents and businesses. Potential mainshock lifeline vulnerability and spatial demand changes will be discerned by superimposing earthquake shaking, liquefaction probability, and landslide probability damage thresholds with lifeline concentrations and with large-capacity shelters. Intersecting high hazard levels and lifeline clusters represent potential lifeline susceptibility hotspots. We will also analyze possible temporal vulnerability and demand changes using an aftershock shaking threshold. The results of this analysis will inform regional lifeline resilience initiatives and response and recovery planning, as well as reveal potential redundancies and weaknesses for Bay Area lifelines. Identified spatial and temporal hotspots can provide stakeholders with a reference for possible systemic vulnerability resulting from an earthquake sequence.

  16. Ecohydrological Interfaces as Dynamic Hotspots of Biogeochemical Cycling

    Science.gov (United States)

    Krause, Stefan; Lewandowski, Joerg; Hannah, David; McDonald, Karlie; Folegot, Silvia; Baranov, Victor

    2016-04-01

    Ecohydrological interfaces, represent the boundaries between water-dependent ecosystems that can alter substantially the fluxes of energy and matter. There is still a critical gap of understanding the organisational principles of the drivers and controls of spatially and temporally variable ecohydrological interface functions. This knowledge gap limits our capacity to efficiently quantify, predict and manage the services provided by complex ecosystems. Many ecohydrological interfaces are characterized by step changes in microbial metabolic activity, steep redox gradients and often even thermodynamic phase shifts, for instance at the interfaces between atmosphere and water or soil matrix and macro-pores interfaces. This paper integrates investigations from point scale laboratory microcosm experiments with reach and subcatchment scale tracer experiments and numerical modeling studies to elaborate similarities in the drivers and controls that constitute the enhanced biogeochemical activity of different types of ecohydrologica interfaces across a range of spatial and temporal scales. We therefore combine smart metabolic activity tracers to quantify the impact of bioturbating benthic fauna onto ecosystem respiration and oxygen consumption and investigate at larger scale, how microbial metabolic activity and carbon turnover at the water-sediment interface are controlled by sediment physical and chemical properties as well as water temperatures. Numerical modeling confirmed that experimentally identified hotspots of streambed biogeochemical cycling were controlled by patterns of physical properties such as hydraulic conductivities or bioavailability of organic matter, impacting on residence time distributions and hence reaction times. In contrast to previous research, our investigations thus confirmed that small-scale variability of physical and chemical interface properties had a major impact on biogeochemical processing at the investigated ecohydrological interfaces

  17. Climate change hotspots in the CMIP5 global climate model ensemble.

    Science.gov (United States)

    Diffenbaugh, Noah S; Giorgi, Filippo

    2012-01-10

    We use a statistical metric of multi-dimensional climate change to quantify the emergence of global climate change hotspots in the CMIP5 climate model ensemble. Our hotspot metric extends previous work through the inclusion of extreme seasonal temperature and precipitation, which exert critical influence on climate change impacts. The results identify areas of the Amazon, the Sahel and tropical West Africa, Indonesia, and the Tibetan Plateau as persistent regional climate change hotspots throughout the 21 st century of the RCP8.5 and RCP4.5 forcing pathways. In addition, areas of southern Africa, the Mediterranean, the Arctic, and Central America/western North America also emerge as prominent regional climate change hotspots in response to intermediate and high levels of forcing. Comparisons of different periods of the two forcing pathways suggest that the pattern of aggregate change is fairly robust to the level of global warming below approximately 2°C of global warming (relative to the late-20 th -century baseline), but not at the higher levels of global warming that occur in the late-21 st -century period of the RCP8.5 pathway, with areas of southern Africa, the Mediterranean, and the Arctic exhibiting particular intensification of relative aggregate climate change in response to high levels of forcing. Although specific impacts will clearly be shaped by the interaction of climate change with human and biological vulnerabilities, our identification of climate change hotspots can help to inform mitigation and adaptation decisions by quantifying the rate, magnitude and causes of the aggregate climate response in different parts of the world.

  18. Imbalance aware lithography hotspot detection: a deep learning approach

    Science.gov (United States)

    Yang, Haoyu; Luo, Luyang; Su, Jing; Lin, Chenxi; Yu, Bei

    2017-07-01

    With the advancement of very large scale integrated circuits (VLSI) technology nodes, lithographic hotspots become a serious problem that affects manufacture yield. Lithography hotspot detection at the post-OPC stage is imperative to check potential circuit failures when transferring designed patterns onto silicon wafers. Although conventional lithography hotspot detection methods, such as machine learning, have gained satisfactory performance, with the extreme scaling of transistor feature size and layout patterns growing in complexity, conventional methodologies may suffer from performance degradation. For example, manual or ad hoc feature extraction in a machine learning framework may lose important information when predicting potential errors in ultra-large-scale integrated circuit masks. We present a deep convolutional neural network (CNN) that targets representative feature learning in lithography hotspot detection. We carefully analyze the impact and effectiveness of different CNN hyperparameters, through which a hotspot-detection-oriented neural network model is established. Because hotspot patterns are always in the minority in VLSI mask design, the training dataset is highly imbalanced. In this situation, a neural network is no longer reliable, because a trained model with high classification accuracy may still suffer from a high number of false negative results (missing hotspots), which is fatal in hotspot detection problems. To address the imbalance problem, we further apply hotspot upsampling and random-mirror flipping before training the network. Experimental results show that our proposed neural network model achieves comparable or better performance on the ICCAD 2012 contest benchmark compared to state-of-the-art hotspot detectors based on deep or representative machine leaning.

  19. An Application Of Facility Location Models With Hotspot Analysis For Optimal Location Of Abattoir Bio-Energy Plant In Anambra State Of Nigeria

    Directory of Open Access Journals (Sweden)

    E. C. Chukwuma

    2015-08-01

    Full Text Available Poor waste management strategy in abattoir in the the study area has needs a major attention considering it negative impacts on man land and water. Sitting of centralized biogas plant in a strategic location in the state would be the major means of combating the environmental challenges of increase in abattoir waste generation as result of population explosion in the state. This study investigates optimal location for sitting central abattoir waste treatment facility in Anambra State of Nigeria using facility location models with hotspot analysis in GIS environment. The result of the study shows that Using centre of gravity model the central location was estimated to be at Xc Yc 6.900953016 6.110157865. Based on inadequacy of the model hotspot analysis operation was done the hotspot analysis delineated clusters of abattoirs significantly higher in bio-wastes production than the overall study area. The hotspot analysis shows that the West regions of the study area has many abattoir that is classified as hotspot abattoirs. Using the hotspot abattoirs as proposed sites for load-distance model three abattoirs were identified as proposed sites- Obosi slaugher house Nkpor Private slaughter house and Oye-olise Ogbunike slaugher house. Their load distance values are 17250.40058 16299.24005 and 18210.14631 respectively. The optimal location for construction of central abattoir bio-waste treatment facility based on the application of these location facility models and hotspot analysis is Nkpor private slaughter house or its environs.

  20. Identifying the Interaction of Vancomycin With Novel pH-Responsive Lipids as Antibacterial Biomaterials Via Accelerated Molecular Dynamics and Binding Free Energy Calculations.

    Science.gov (United States)

    Ahmed, Shaimaa; Vepuri, Suresh B; Jadhav, Mahantesh; Kalhapure, Rahul S; Govender, Thirumala

    2018-06-01

    Nano-drug delivery systems have proven to be an efficient formulation tool to overcome the challenges with current antibiotics therapy and resistance. A series of pH-responsive lipid molecules were designed and synthesized for future liposomal formulation as a nano-drug delivery system for vancomycin at the infection site. The structures of these lipids differ from each other in respect of hydrocarbon tails: Lipid1, 2, 3 and 4 have stearic, oleic, linoleic, and linolenic acid hydrocarbon chains, respectively. The impact of variation in the hydrocarbon chain in the lipid structure on drug encapsulation and release profile, as well as mode of drug interaction, was investigated using molecular modeling analyses. A wide range of computational tools, including accelerated molecular dynamics, normal molecular dynamics, binding free energy calculations and principle component analysis, were applied to provide comprehensive insight into the interaction landscape between vancomycin and the designed lipid molecules. Interestingly, both MM-GBSA and MM-PBSA binding affinity calculations using normal molecular dynamics and accelerated molecular dynamics trajectories showed a very consistent trend, where the order of binding affinity towards vancomycin was lipid4 > lipid1 > lipid2 > lipid3. From both normal molecular dynamics and accelerated molecular dynamics, the interaction of lipid3 with vancomycin is demonstrated to be the weakest (∆G binding  = -2.17 and -11.57, for normal molecular dynamics and accelerated molecular dynamics, respectively) when compared to other complexes. We believe that the degree of unsaturation of the hydrocarbon chain in the lipid molecules may impact on the overall conformational behavior, interaction mode and encapsulation (wrapping) of the lipid molecules around the vancomycin molecule. This thorough computational analysis prior to the experimental investigation is a valuable approach to guide for predicting the encapsulation

  1. SLR-induced temporal and spatial changes in hotspots to storms along the Catalan coast

    Science.gov (United States)

    Jiménez, Jose A.; Sanuy, Marc; Valdemoro, Herminia

    2017-04-01

    Coastal hotspots to storms can be simply defined as locations where the magnitude of the storm-induced risk is significantly higher than neighbouring areas for a given probability of occurrence. Their distribution along the coast depends on the magnitude of storm-induced hazards and on the coastal resilient capacity. Increasing damages observed in our coasts during the last decades have driven the need to include specific chapters on risk management in ICZM plans. In this context, the identification of hotspots is one of the first points to be considered. This permits to better allocate resources for risk management by concentrating efforts in specific locations. Within this context, we have identified hotspots along the Catalan coast (Spanish Mediterranean) to storm-induced erosion and inundation hazards. This has been done by using the methodology developed within the RISCKIT EU project where storm-induced hazards (erosion and inundation) are characterised in probabilistic terms by using simple inundation and erosion models as a function of water level and wave climates and local coastal morphology. The final result was a set of inundation and erosion hotspots along the coast under current conditions for selected probabilities of occurrences, P. For low return periods, Tr, few hotspots appear and they represent coastal locations frequently affected by the corresponding hazard. On the other, for high Tr, a larger number (and of larger extension) of hotspots appear, that although less frequently affected, they are subjected to a larger impact. Although this is valuable information for coastal managers, it is only valid for making decisions for a short time horizon or under steady conditions. However, since the proper time scale for coastal planning is in the order of several decades, it is not likely that conditions will remain steady. Thus, although most of existing predictions of climate-induce changes in storminess in the Mediterranean indicate the absence of

  2. High road utilizers surveys compared to police data for road traffic crash hotspot localization in Rwanda and Sri Lanka.

    Science.gov (United States)

    Staton, Catherine A; De Silva, Vijitha; Krebs, Elizabeth; Andrade, Luciano; Rulisa, Stephen; Mallawaarachchi, Badra Chandanie; Jin, Kezhi; RicardoVissoci, Joao; Østbye, Truls

    2016-01-20

    Road traffic crashes (RTCs) are a leading cause of death. In low and middle income countries (LMIC) data to conduct hotspot analyses and safety audits are usually incomplete, poor quality, and not computerized. Police data are often limited, but there are no alternative gold standards. This project evaluates high road utilizer surveys as an alternative to police data to identify RTC hotspots. Retrospective police RTC data was compared to prospective data from high road utilizer surveys regarding dangerous road locations. Spatial analysis using geographic information systems was used to map dangerous locations and identify RTC hotspots. We assessed agreement (Cohen's Kappa), sensitivity/specificity, and cost differences. In Rwanda police data identified 1866 RTC locations from 2589 records while surveys identified 1264 locations from 602 surveys. In Sri Lanka, police data identified 721 RTC locations from 752 records while survey data found 3000 locations from 300 surveys. There was high agreement (97 %, 83 %) and kappa (0.60, 0.60) for Rwanda and Sri Lanka respectively. Sensitivity and specificity are 92 % and 95 % for Rwanda and 74 % and 93 % for Sri Lanka. The cost per crash location identified was $2.88 for police and $2.75 for survey data in Rwanda and $2.75 for police and $1.21 for survey data in Sri Lanka. Surveys to locate RTC hotspots have high sensitivity and specificity compared to police data. Therefore, surveys can be a viable, inexpensive, and rapid alternative to the use of police data in LMIC.

  3. Higher 5-HT1A autoreceptor binding as an endophenotype for major depressive disorder identified in high risk offspring - A pilot study.

    Science.gov (United States)

    Milak, Matthew S; Pantazatos, Spiro; Rashid, Rain; Zanderigo, Francesca; DeLorenzo, Christine; Hesselgrave, Natalie; Ogden, R Todd; Oquendo, Maria A; Mulhern, Stephanie T; Miller, Jeffrey M; Burke, Ainsley K; Parsey, Ramin V; Mann, J John

    2018-04-13

    Higher serotonin-1A (5-HT 1A ) receptor binding potential (BP F ) has been found in major depressive disorder (MDD) during and between major depressive episodes. We investigated whether higher 5-HT 1A binding is a biologic trait transmitted to healthy high risk (HR) offspring of MDD probands. Data were collected contemporaneously from: nine HR, 30 depressed not-recently medicated (NRM) MDD, 18 remitted NRM MDD, 51 healthy volunteer (HV) subjects. Subjects underwent positron emission tomography (PET) using [ 11 C]WAY100635 to quantify 5-HT 1A BP F , estimated using metabolite, free fraction-corrected arterial input function and cerebellar white matter as reference region. Multivoxel pattern analyses (MVPA) of PET data evaluated group status classification of individuals. When tested across 13 regions of interest, an effect of diagnosis is found on BP F which remains significant after correction for sex, age, injected mass and dose: HR have higher BP F than HV (84.3% higher in midbrain raphe, 40.8% higher in hippocampus, mean BP F across all 13 brain regions is 49.9% ± 11.8% higher). Voxel-level BP F maps distinguish HR vs. HV. Elevated 5-HT 1A BP F appears to be a familially transmitted trait abnormality. Future studies are needed to replicate this finding in a larger cohort and demonstrate the link to the familial transmission of mood disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Biodiversity hotspots house most undiscovered plant species.

    Science.gov (United States)

    Joppa, Lucas N; Roberts, David L; Myers, Norman; Pimm, Stuart L

    2011-08-09

    For most organisms, the number of described species considerably underestimates how many exist. This is itself a problem and causes secondary complications given present high rates of species extinction. Known numbers of flowering plants form the basis of biodiversity "hotspots"--places where high levels of endemism and habitat loss coincide to produce high extinction rates. How different would conservation priorities be if the catalog were complete? Approximately 15% more species of flowering plant are likely still undiscovered. They are almost certainly rare, and depending on where they live, suffer high risks of extinction from habitat loss and global climate disruption. By using a model that incorporates taxonomic effort over time, regions predicted to contain large numbers of undiscovered species are already conservation priorities. Our results leave global conservation priorities more or less intact, but suggest considerably higher levels of species imperilment than previously acknowledged.

  5. An underappreciated hotspot of antibiotic resistance

    DEFF Research Database (Denmark)

    Chen, Qing-Lin; Li, Hu; Zhou, Xin-Yuan

    2017-01-01

    Landfills are so far the most common practice for the disposals of municipal solid waste (MSW) worldwide. Since MSW landfill receives miscellaneous wastes, including unused/expired antibiotics and bioactive wastes, it gradually becomes a huge potential bioreactor for breeding antibiotic resistance....... Antibiotic resistance genes (ARGs) in landfill can flow to the environment through leakage of landfill leachate and pose a risk to public health. Using high throughput quantitative Polymerase Chain Reaction (HT-qPCR), we investigated the prevalence, diversity of ARGs and its association with various mobile...... be the potential hosts of ARGs. These findings provide evidence that groundwater near MSW landfill is an underappreciated hotspot of antibiotic resistance and contribute to the spread of ARGs via the flowing contaminated groundwater....

  6. HAMS: High-Affinity Mass Spectrometry Screening. A High-Throughput Screening Method for Identifying the Tightest-Binding Lead Compounds for Target Proteins with No False Positive Identifications.

    Science.gov (United States)

    Imaduwage, Kasun P; Go, Eden P; Zhu, Zhikai; Desaire, Heather

    2016-11-01

    A major challenge in drug discovery is the identification of high affinity lead compounds that bind a particular target protein; these leads are typically identified by high throughput screens. Mass spectrometry has become a detection method of choice in drug screening assays because the target and the ligand need not be modified. Label-free assays are advantageous because they can be developed more rapidly than assays requiring labels, and they eliminate the risk of the label interfering with the binding event. However, in commonly used MS-based screening methods, detection of false positives is a major challenge. Here, we describe a detection strategy designed to eliminate false positives. In this approach, the protein and the ligands are incubated together, and the non-binders are separated for detection. Hits (protein binders) are not detectable by MS after incubation with the protein, but readily identifiable by MS when the target protein is not present in the incubation media. The assay was demonstrated using three different proteins and hundreds of non-inhibitors; no false positive hits were identified in any experiment. The assay can be tuned to select for ligands of a particular binding affinity by varying the quantity of protein used and the immobilization method. As examples, the method selectively detected inhibitors that have K i values of 0.2 μM, 50 pM, and 700 pM. These findings demonstrate that the approach described here compares favorably with traditional MS-based screening methods. Graphical Abstract ᅟ.

  7. HIV-1 vaccine-induced T-cell responses cluster in epitope hotspots that differ from those induced in natural infection with HIV-1.

    Science.gov (United States)

    Hertz, Tomer; Ahmed, Hasan; Friedrich, David P; Casimiro, Danilo R; Self, Steven G; Corey, Lawrence; McElrath, M Juliana; Buchbinder, Susan; Horton, Helen; Frahm, Nicole; Robertson, Michael N; Graham, Barney S; Gilbert, Peter

    2013-01-01

    Several recent large clinical trials evaluated HIV vaccine candidates that were based on recombinant adenovirus serotype 5 (rAd-5) vectors expressing HIV-derived antigens. These vaccines primarily elicited T-cell responses, which are known to be critical for controlling HIV infection. In the current study, we present a meta-analysis of epitope mapping data from 177 participants in three clinical trials that tested two different HIV vaccines: MRKAd-5 HIV and VRC-HIVAD014-00VP. We characterized the population-level epitope responses in these trials by generating population-based epitope maps, and also designed such maps using a large cohort of 372 naturally infected individuals. We used these maps to address several questions: (1) Are vaccine-induced responses randomly distributed across vaccine inserts, or do they cluster into immunodominant epitope hotspots? (2) Are the immunodominance patterns observed for these two vaccines in three vaccine trials different from one another? (3) Do vaccine-induced hotspots overlap with epitope hotspots induced by chronic natural infection with HIV-1? (4) Do immunodominant hotspots target evolutionarily conserved regions of the HIV genome? (5) Can epitope prediction methods be used to identify these hotspots? We found that vaccine responses clustered into epitope hotspots in all three vaccine trials and some of these hotspots were not observed in chronic natural infection. We also found significant differences between the immunodominance patterns generated in each trial, even comparing two trials that tested the same vaccine in different populations. Some of the vaccine-induced immunodominant hotspots were located in highly variable regions of the HIV genome, and this was more evident for the MRKAd-5 HIV vaccine. Finally, we found that epitope prediction methods can partially predict the location of vaccine-induced epitope hotspots. Our findings have implications for vaccine design and suggest a framework by which different

  8. Laser interaction effects of electromagnetic absorption and microstructural defects on hot-spot formation in RDX-PCTFE energetic aggregates

    International Nuclear Information System (INIS)

    Brown, Judith A; LaBarbera, Darrell A; Zikry, Mohammed A

    2014-01-01

    Hot-spot formation in energetic aggregates subjected to dynamic pressure loading and laser irradiation has been investigated. Specialized finite-element techniques with a dislocation-density-based crystalline plasticity constitutive formulation and thermo-mechanical coupling of heat conduction, adiabatic heating, laser heating and thermal decomposition were used to predict hot-spot formation in RDX–polymer aggregates subjected to dynamic pressures and laser energies. The effects of the electromagnetic absorption coefficient coupled with void distribution and spacing, grain morphology, crystal–binder interactions and dislocation densities were analyzed to determine their influence on the time, location and mechanisms of hot-spot formation. Four different mechanisms for hot-spot initiation under dynamic laser and pressure loads were identified, which depend on the localization of plastic shear strain and laser heat absorption within the aggregate. The predictions indicate that hot-spot formation is accelerated by higher absorption coefficients and by localized plastic deformations that occur in areas of significant laser heating. (paper)

  9. Spatio-temporal variations of conservation hotspots based on ecosystem services in Xishuangbanna, Southwest China.

    Science.gov (United States)

    Liu, Shiliang; Yin, Yijie; Cheng, Fangyan; Hou, Xiaoyun; Dong, Shikui; Wu, Xue

    2017-01-01

    Integrating biodiversity and ecosystem services (BES) has been viewed as an appropriate approach to identifying conservation priorities. Taking Xishuangbanna tropical region in Southwest China, different BESs (habitat quality [used as a proxy for biodiversity], carbon storage, and water yield) were quantified using the InVEST model and conservation hotspots from 1976, 1990, and 2010 were identified by overlapping and ranking the service layers. Results showed that BESs areas were unevenly distributed. High habitat quality and carbon storage areas located in the eastern part of the region were mainly occupied by broad-leaved forest, while high water yield areas were covered by grassland and tropical forests. Recognized hotspots were primarily composed of the broad-leaved forest and shrub grassland. However, these habitat types declined by nearly 50% from 1.25×105 ha to 0.63×105 ha and became more fragmented during the study period. We also found that the sub-watersheds which decreased in BES had fewer hotspots distributed and suffered greater landscape fragmentation. Our study further explored the impacts of land-use conversion on BES, and illustrated the necessity and feasibility of BESs in identifying potential conservation areas.

  10. Restoring Wood-Rich Hotspots in Mountain Stream Networks

    Science.gov (United States)

    Wohl, E.; Scott, D.

    2016-12-01

    Mountain streams commonly include substantial longitudinal variability in valley and channel geometry, alternating repeatedly between steep, narrow and relatively wide, low gradient segments. Segments that are wider and lower gradient than neighboring steeper sections are hotspots with respect to: retention of large wood (LW) and finer sediment and organic matter; uptake of nutrients; and biomass and biodiversity of aquatic and riparian organisms. These segments are also more likely to be transport-limited with respect to floodplain and instream LW. Management designed to protect and restore riverine LW and the physical and ecological processes facilitated by the presence of LW is likely to be most effective if focused on relatively low-gradient stream segments. These segments can be identified using a simple, reach-scale gradient analysis based on high-resolution DEMs, with field visits to identify factors that potentially limit or facilitate LW recruitment and retention, such as forest disturbance history or land use. Drawing on field data from the western US, this presentation outlines a procedure for mapping relatively low-gradient segments in a stream network and for identifying those segments where LW reintroduction or retention is most likely to balance maximizing environmental benefits derived from the presence of LW while minimizing hazards associated with LW.

  11. Detecting hotspots of atmosphere–vegetation interaction via slowing down – Part 2: Application to a global climate model

    Directory of Open Access Journals (Sweden)

    S. Bathiany

    2013-02-01

    Full Text Available Early warning signals (EWS have become a popular statistical tool to infer stability properties of the climate system. In Part 1 of this two-part paper we have presented a diagnostic method to find the hotspot of a sudden transition as opposed to regions that experience an externally induced tipping as a mere response. Here, we apply our method to the atmosphere–vegetation model PlanetSimulator (PlaSim – VECODE using a regression model. For each of two vegetation collapses in PlaSim-VECODE, we identify a hotspot of one particular grid cell. We demonstrate with additional experiments that the detected hotspots are indeed a particularly sensitive region in the model and give a physical explanation for these results. The method can thus provide information on the causality of sudden transitions and may help to improve the knowledge on the vulnerability of certain subsystems in climate models.

  12. Phonon emission from self-heating hotspots into He II

    International Nuclear Information System (INIS)

    Schulze, H.-J.; Keck, K.

    1985-01-01

    Self-heating effects in superconducting films or whiskers can produce several hotspots distributed along the sample in the transition range between its superconducting and completely normal state. To obtain information about the temperature distribution along the film in this transition range and the emission of phonons from hotspots into the helium bath, we moved thin carbon filaments close to the film surfaces. By means of the data and the current-voltage characteristics of the films conclusions can be drawn about the number and the size of the hotspots. (author)

  13. Reticulomics: Protein-Protein Interaction Studies with Two Plasmodesmata-Localized Reticulon Family Proteins Identify Binding Partners Enriched at Plasmodesmata, Endoplasmic Reticulum, and the Plasma Membrane.

    Science.gov (United States)

    Kriechbaumer, Verena; Botchway, Stanley W; Slade, Susan E; Knox, Kirsten; Frigerio, Lorenzo; Oparka, Karl; Hawes, Chris

    2015-11-01

    The endoplasmic reticulum (ER) is a ubiquitous organelle that plays roles in secretory protein production, folding, quality control, and lipid biosynthesis. The cortical ER in plants is pleomorphic and structured as a tubular network capable of morphing into flat cisternae, mainly at three-way junctions, and back to tubules. Plant reticulon family proteins (RTNLB) tubulate the ER by dimerization and oligomerization, creating localized ER membrane tensions that result in membrane curvature. Some RTNLB ER-shaping proteins are present in the plasmodesmata (PD) proteome and may contribute to the formation of the desmotubule, the axial ER-derived structure that traverses primary PD. Here, we investigate the binding partners of two PD-resident reticulon proteins, RTNLB3 and RTNLB6, that are located in primary PD at cytokinesis in tobacco (Nicotiana tabacum). Coimmunoprecipitation of green fluorescent protein-tagged RTNLB3 and RTNLB6 followed by mass spectrometry detected a high percentage of known PD-localized proteins as well as plasma membrane proteins with putative membrane-anchoring roles. Förster resonance energy transfer by fluorescence lifetime imaging microscopy assays revealed a highly significant interaction of the detected PD proteins with the bait RTNLB proteins. Our data suggest that RTNLB proteins, in addition to a role in ER modeling, may play important roles in linking the cortical ER to the plasma membrane. © 2015 American Society of Plant Biologists. All Rights Reserved.

  14. Mutational analysis of the EMCV 2A protein identifies a nuclear localization signal and an eIF4E binding site

    International Nuclear Information System (INIS)

    Groppo, Rachel; Brown, Bradley A.; Palmenberg, Ann C.

    2011-01-01

    Cardioviruses have a unique 2A protein (143 aa). During genome translation, the encephalomyocarditis virus (EMCV) 2A is released through a ribosome skipping event mitigated through C-terminal 2A sequences and by subsequent N-terminal reaction with viral 3C pro . Although viral replication is cytoplasmic, mature 2A accumulates in nucleoli shortly after infection. Some protein also transiently associates with cytoplasmic 40S ribosomal subunits, an activity contributing to inhibition of cellular cap-dependent translation. Cardiovirus sequences predict an eIF4E binding site (aa 126-134) and a nuclear localization signal (NLS, aa 91-102), within 2A, both of which are functional during EMCV infection. Point mutations preventing eIF4E:2A interactions gave small-plaque phenotype viruses, but still inhibited cellular cap-dependent translation. Deletions within the NLS motif relocalized 2A to the cytoplasm and abrogated the inhibition of cap-dependent translation. A fusion protein linking the 2A NLS to eGFP was sufficient to redirect the reporter to the nucleus but not into nucleoli.

  15. Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120.

    Science.gov (United States)

    deCamp, Allan C; Rolland, Morgane; Edlefsen, Paul T; Sanders-Buell, Eric; Hall, Breana; Magaret, Craig A; Fiore-Gartland, Andrew J; Juraska, Michal; Carpp, Lindsay N; Karuna, Shelly T; Bose, Meera; LePore, Steven; Miller, Shana; O'Sullivan, Annemarie; Poltavee, Kultida; Bai, Hongjun; Dommaraju, Kalpana; Zhao, Hong; Wong, Kim; Chen, Lennie; Ahmed, Hasan; Goodman, Derrick; Tay, Matthew Z; Gottardo, Raphael; Koup, Richard A; Bailer, Robert; Mascola, John R; Graham, Barney S; Roederer, Mario; O'Connell, Robert J; Michael, Nelson L; Robb, Merlin L; Adams, Elizabeth; D'Souza, Patricia; Kublin, James; Corey, Lawrence; Geraghty, Daniel E; Frahm, Nicole; Tomaras, Georgia D; McElrath, M Juliana; Frenkel, Lisa; Styrchak, Sheila; Tovanabutra, Sodsai; Sobieszczyk, Magdalena E; Hammer, Scott M; Kim, Jerome H; Mullins, James I; Gilbert, Peter B

    2017-01-01

    Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector.

  16. Hotspots of human nutrition: Micronutrient supply, demand, and pollinator dependence

    Science.gov (United States)

    Dombeck, E.; Chaplin-Kramer, R.; Mueller, M.; Mueller, N. D.; Foley, J. A.

    2012-12-01

    While our caloric needs can mostly be met by wind-pollinated crops such as cereals, a recent analysis of USDA data shows that animal-pollinated crops contain the vast majority of many essential nutrients, including vitamins A and C, calcium, fluoride, and folic acid. In this work we combined global crop yield data with data on nutritional content in each crop to map nutrient production around the world, and to illustrate the value of pollination services to human nutrition. Spatially explicit crop yields (at 5 min resolution) were multiplied by crop nutrient content and by crop dependence on pollination to map where reductions in total nutrient production would occur if pollination services were removed. Nutrient demand maps (human nutrient requirements multiplied by population density) were generated to identify regions where local reduction in pollination services could threaten nutritional security. Nutrient deficiency maps (nutrient supply minus nutrient demand) were also created to identify hotspots where local crop production is not adequate to meet local nutritional needs.

  17. Genome-wide signatures of 'rearrangement hotspots' within segmental duplications in humans.

    Directory of Open Access Journals (Sweden)

    Mohammed Uddin

    Full Text Available The primary objective of this study was to create a genome-wide high resolution map (i.e., >100 bp of 'rearrangement hotspots' which can facilitate the identification of regions capable of mediating de novo deletions or duplications in humans. A hierarchical method was employed to fragment segmental duplications (SDs into multiple smaller SD units. Combining an end space free pairwise alignment algorithm with a 'seed and extend' approach, we have exhaustively searched 409 million alignments to detect complex structural rearrangements within the reference-guided assembly of the NA18507 human genome (18× coverage, including the previously identified novel 4.8 Mb sequence from de novo assembly within this genome. We have identified 1,963 rearrangement hotspots within SDs which encompass 166 genes and display an enrichment of duplicated gene nucleotide variants (DNVs. These regions are correlated with increased non-allelic homologous recombination (NAHR event frequency which presumably represents the origin of copy number variations (CNVs and pathogenic duplications/deletions. Analysis revealed that 20% of the detected hotspots are clustered within the proximal and distal SD breakpoints flanked by the pathogenic deletions/duplications that have been mapped for 24 NAHR-mediated genomic disorders. FISH Validation of selected complex regions revealed 94% concordance with in silico localization of the highly homologous derivatives. Other results from this study indicate that intra-chromosomal recombination is enhanced in genic compared with agenic duplicated regions, and that gene desert regions comprising SDs may represent reservoirs for creation of novel genes. The generation of genome-wide signatures of 'rearrangement hotspots', which likely serve as templates for NAHR, may provide a powerful approach towards understanding the underlying mutational mechanism(s for development of constitutional and acquired diseases.

  18. Assessment of outdoor radiofrequency electromagnetic field exposure through hotspot localization using kriging-based sequential sampling

    Energy Technology Data Exchange (ETDEWEB)

    Aerts, Sam, E-mail: sam.aerts@intec.ugent.be; Deschrijver, Dirk; Verloock, Leen; Dhaene, Tom; Martens, Luc; Joseph, Wout

    2013-10-15

    iterative measurement and modeling method for outdoor RF-EMF exposure. • Hotspots are rapidly identified, and accurately characterized. • An accurate graphical representation, or heat map, is created, using kriging. • Random validation shows good correlation (0.7) and low relative errors (2 dB)

  19. Assessment of outdoor radiofrequency electromagnetic field exposure through hotspot localization using kriging-based sequential sampling

    International Nuclear Information System (INIS)

    Aerts, Sam; Deschrijver, Dirk; Verloock, Leen; Dhaene, Tom; Martens, Luc; Joseph, Wout

    2013-01-01

    iterative measurement and modeling method for outdoor RF-EMF exposure. • Hotspots are rapidly identified, and accurately characterized. • An accurate graphical representation, or heat map, is created, using kriging. • Random validation shows good correlation (0.7) and low relative errors (2 dB)

  20. Polarization observations of DA240: structure of a hotspot

    International Nuclear Information System (INIS)

    Tsien, S.C.

    1982-01-01

    We present observations of the large-scale structure of the giant radio galaxy DA 240 at 0.15 and 1.4 GHz and high-resolution observations of the hotspot in its eastern lobe at 2.7 and 5.0 GHz. It is shown that the large-scale structure of DA 240 at 0.15 GHz is closely similar to that at 1.4 GHz. An age of about 4 x 10 7 yr is estimated from the spectral index. The hotspot contains a compact component of approximately 2 in size, and is strongly polarized, up to 50 to 60 per cent in its south-east region. The projected magnetic field in the hotspot runs nearly parallel to the two main elongated subcomponents. The thermal electron density in the hotspot is estimated to be -5 cm -3 . (author)

  1. Transportation conformity particulate matter hot-spot air quality modeling.

    Science.gov (United States)

    2013-07-01

    In light of the new development in particulate matter (PM) hot-spot regulations and Illinois Department : of Transportation (IDOT)s National Environmental Policy Act (NEPA) documentation requirements, : this project is intended to (1) perform and ...

  2. Ideas from the global climate change hotspot research | IDRC ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2017-05-09

    May 9, 2017 ... Ideas from the global climate change hotspot research ... The Collaborative Adaptation Research Initiative in Africa and Asia (CARIAA) ... the decisions they need to make about investment choices and development options, ...

  3. Combined serial analysis of gene expression and transcription factor binding site prediction identifies novel-candidate-target genes of Nr2e1 in neocortex development.

    Science.gov (United States)

    Schmouth, Jean-François; Arenillas, David; Corso-Díaz, Ximena; Xie, Yuan-Yun; Bohacec, Slavita; Banks, Kathleen G; Bonaguro, Russell J; Wong, Siaw H; Jones, Steven J M; Marra, Marco A; Simpson, Elizabeth M; Wasserman, Wyeth W

    2015-07-24

    Nr2e1 (nuclear receptor subfamily 2, group e, member 1) encodes a transcription factor important in neocortex development. Previous work has shown that nuclear receptors can have hundreds of target genes, and bind more than 300 co-interacting proteins. However, recognition of the critical role of Nr2e1 in neural stem cells and neocortex development is relatively recent, thus the molecular mechanisms involved for this nuclear receptor are only beginning to be understood. Serial analysis of gene expression (SAGE), has given researchers both qualitative and quantitative information pertaining to biological processes. Thus, in this work, six LongSAGE mouse libraries were generated from laser microdissected tissue samples of dorsal VZ/SVZ (ventricular zone and subventricular zone) from the telencephalon of wild-type (Wt) and Nr2e1-null embryos at the critical development ages E13.5, E15.5, and E17.5. We then used a novel approach, implementing multiple computational methods followed by biological validation to further our understanding of Nr2e1 in neocortex development. In this work, we have generated a list of 1279 genes that are differentially expressed in response to altered Nr2e1 expression during in vivo neocortex development. We have refined this list to 64 candidate direct-targets of NR2E1. Our data suggested distinct roles for Nr2e1 during different neocortex developmental stages. Most importantly, our results suggest a possible novel pathway by which Nr2e1 regulates neurogenesis, which includes Lhx2 as one of the candidate direct-target genes, and SOX9 as a co-interactor. In conclusion, we have provided new candidate interacting partners and numerous well-developed testable hypotheses for understanding the pathways by which Nr2e1 functions to regulate neocortex development.

  4. Structural insight into exosite binding and discovery of novel exosite inhibitors of botulinum neurotoxin serotype A through in silico screening

    Science.gov (United States)

    Hu, Xin; Legler, Patricia M.; Southall, Noel; Maloney, David J.; Simeonov, Anton; Jadhav, Ajit

    2014-07-01

    Botulinum neurotoxin serotype A (BoNT/A) is the most lethal toxin among the Tier 1 Select Agents. Development of potent and selective small molecule inhibitors against BoNT/A zinc metalloprotease remains a challenging problem due to its exceptionally large substrate binding surface and conformational plasticity. The exosites of the catalytic domain of BoNT/A are intriguing alternative sites for small molecule intervention, but their suitability for inhibitor design remains largely unexplored. In this study, we employed two recently identified exosite inhibitors, D-chicoric acid and lomofungin, to probe the structural features of the exosites and molecular mechanisms of synergistic inhibition. The results showed that D-chicoric acid favors binding at the α-exosite, whereas lomofungin preferentially binds at the β-exosite by mimicking the substrate β-sheet binding interaction. Molecular dynamics simulations and binding interaction analysis of the exosite inhibitors with BoNT/A revealed key elements and hotspots that likely contribute to the inhibitor binding and synergistic inhibition. Finally, we performed database virtual screening for novel inhibitors of BoNT/A targeting the exosites. Hits C1 and C2 showed non-competitive inhibition and likely target the α- and β-exosites, respectively. The identified exosite inhibitors may provide novel candidates for structure-based development of therapeutics against BoNT/A intoxication.

  5. Fish-derived nutrient hotspots shape coral reef benthic communities.

    Science.gov (United States)

    Shantz, Andrew A; Ladd, Mark C; Schrack, Elizabeth; Burkepile, Deron E

    2015-12-01

    Animal-derived nutrients play an important role in structuring nutrient regimes within and between ecosystems. When animals undergo repetitive, aggregating behavior through time, they can create nutrient hotspots where rates of biogeochemical activity are higher than those found in the surrounding environment. In turn, these hotspots can influence ecosystem processes and community structure. We examined the potential for reef fishes from the family Haemulidae (grunts) to create nutrient hotspots and the potential impact of these hotspots on reef communities. To do so, we tracked the schooling locations of diurnally migrating grunts, which shelter at reef sites during the day but forage off reef each night, and measured the impact of these fish schools on benthic communities. We found that grunt schools showed a high degree of site fidelity, repeatedly returning to the same coral heads. These aggregations created nutrient hotspots around coral heads where nitrogen and phosphorus delivery was roughly 10 and 7 times the respective rates of delivery to structurally similar sites that lacked schools of these fishes. In turn, grazing rates of herbivorous fishes at grunt-derived hotspots were approximately 3 times those of sites where grunts were rare. These differences in nutrient delivery and grazing led to distinct benthic communities with higher cover of crustose coralline algae and less total algal abundance at grunt aggregation sites. Importantly, coral growth was roughly 1.5 times greater at grunt hotspots, likely due to the important nutrient subsidy. Our results suggest that schooling reef fish and their nutrient subsidies play an important role in mediating community structure on coral reefs and that overfishing may have important negative consequences on ecosystem functions. As such, management strategies must consider mesopredatory fishes in addition to current protection often offered to herbivores and top-tier predators. Furthermore, our results suggest that

  6. Quantile-based permutation thresholds for quantitative trait loci hotspots.

    Science.gov (United States)

    Neto, Elias Chaibub; Keller, Mark P; Broman, Andrew F; Attie, Alan D; Jansen, Ritsert C; Broman, Karl W; Yandell, Brian S

    2012-08-01

    Quantitative trait loci (QTL) hotspots (genomic locations affecting many traits) are a common feature in genetical genomics studies and are biologically interesting since they may harbor critical regulators. Therefore, statistical procedures to assess the significance of hotspots are of key importance. One approach, randomly allocating observed QTL across the genomic locations separately by trait, implicitly assumes all traits are uncorrelated. Recently, an empirical test for QTL hotspots was proposed on the basis of the number of traits that exceed a predetermined LOD value, such as the standard permutation LOD threshold. The permutation null distribution of the maximum number of traits across all genomic locations preserves the correlation structure among the phenotypes, avoiding the detection of spurious hotspots due to nongenetic correlation induced by uncontrolled environmental factors and unmeasured variables. However, by considering only the number of traits above a threshold, without accounting for the magnitude of the LOD scores, relevant information is lost. In particular, biologically interesting hotspots composed of a moderate to small number of traits with strong LOD scores may be neglected as nonsignificant. In this article we propose a quantile-based permutation approach that simultaneously accounts for the number and the LOD scores of traits within the hotspots. By considering a sliding scale of mapping thresholds, our method can assess the statistical significance of both small and large hotspots. Although the proposed approach can be applied to any type of heritable high-volume "omic" data set, we restrict our attention to expression (e)QTL analysis. We assess and compare the performances of these three methods in simulations and we illustrate how our approach can effectively assess the significance of moderate and small hotspots with strong LOD scores in a yeast expression data set.

  7. Prdm9 Controls Activation of Mammalian Recombination Hotspots

    OpenAIRE

    Parvanov, Emil D.; Petkov, Petko M.; Paigen, Kenneth

    2009-01-01

    Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, assures the orderly segregation of meiotic chromosomes and creates genetic variation among offspring. A locus on mouse Chr 17, that controls activation of recombination at multiple distant hotspots, has been mapped within a 181 Kb interval, three of whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone H3K4 trimethylase that is uniquel...

  8. Investigating avian influenza infection hotspots in old-world shorebirds.

    Directory of Open Access Journals (Sweden)

    Nicolas Gaidet

    Full Text Available Heterogeneity in the transmission rates of pathogens across hosts or environments may produce disease hotspots, which are defined as specific sites, times or species associations in which the infection rate is consistently elevated. Hotspots for avian influenza virus (AIV in wild birds are largely unstudied and poorly understood. A striking feature is the existence of a unique but consistent AIV hotspot in shorebirds (Charadriiformes associated with a single species at a specific location and time (ruddy turnstone Arenaria interpres at Delaware Bay, USA, in May. This unique case, though a valuable reference, limits our capacity to explore and understand the general properties of AIV hotspots in shorebirds. Unfortunately, relatively few shorebirds have been sampled outside Delaware Bay and they belong to only a few shorebird families; there also has been a lack of consistent oropharyngeal sampling as a complement to cloacal sampling. In this study we looked for AIV hotspots associated with other shorebird species and/or with some of the larger congregation sites of shorebirds in the old world. We assembled and analysed a regionally extensive dataset of AIV prevalence from 69 shorebird species sampled in 25 countries across Africa and Western Eurasia. Despite this diverse and extensive coverage we did not detect any new shorebird AIV hotspots. Neither large shorebird congregation sites nor the ruddy turnstone were consistently associated with AIV hotspots. We did, however, find a low but widespread circulation of AIV in shorebirds that contrast with the absence of AIV previously reported in shorebirds in Europe. A very high AIV antibody prevalence coupled to a low infection rate was found in both first-year and adult birds of two migratory sandpiper species, suggesting the potential existence of an AIV hotspot along their migratory flyway that is yet to be discovered.

  9. A measurement concept for hot-spot BRDFs from space

    Energy Technology Data Exchange (ETDEWEB)

    Gerstl, S.A.W.

    1996-09-01

    Several concepts for canopy hot-spot measurements from space have been investigated. The most promising involves active illumination and bistatic detection that would allow hot-spot angular distribution (BRDF) measurements from space in a search-light mode. The concept includes a pointable illumination source, such as a laser operating at an atmospheric window wavelength, coupled with a number of high spatial-resolution detectors that are clustered around the illumination source in space, receiving photons nearly coaxial with the reto-reflection direction. Microwave control and command among the satellite cluster would allow orienting the direction of the laser beam as well as the focusing detectors simultaneously so that the coupled system can function like a search light with almost unlimited pointing capabilities. The concept is called the Hot-Spot Search-Light (HSSL) satellite. A nominal satellite altitude of 600 km will allow hot-spot BRDF measurements out to about 18 degrees phase angle. The distributed are taking radiometric measurements of the intensity wings of the hot-spot angular distribution without the need for complex imaging detectors. The system can be operated at night for increased signal-to-noise ratio. This way the hot-spot angular signatures can be quantified and parameterized in sufficient detail to extract the biophysical information content of plant architectures.

  10. A measurement concept for hot-spot BRDFs from space

    Science.gov (United States)

    Gerstl, S.A.W.

    1996-01-01

    Several concepts for canopy hot-spot measurements from space have been investigated. The most promising involves active illumination and bistatic detection that would allow hot-spot angular distribution (BRDF) measurements from space in a search-light mode. The concept includes a pointable illumination source, such as a laser operating at an atmospheric window wavelength, coupled with a number of high spatial-resolution detectors that are clustered around the illumination source in space, receiving photons nearly coaxial with the reto-reflection direction. Microwave control and command among the satellite cluster would allow orienting the direction of the laser beam as well as the focusing detectors simultaneously so that the coupled system can function like a search light with almost unlimited pointing capabilities. The concept is called the Hot-Spot Search-Light (HSSL) satellite. A nominal satellite altitude of 600 km will allow hot-spot BRDF measurements out to about 18 degrees phase angle. The distributed are taking radiometric measurements of the intensity wings of the hot-spot angular distribution without the need for complex imaging detectors. The system can be operated at night for increased signal-to-noise ratio. This way the hot-spot angular signatures can be quantified and parameterized in sufficient detail to extract the biophysical information content of plant architectures.

  11. Coastal leatherback turtles reveal conservation hotspot

    Science.gov (United States)

    Robinson, Nathan J.; Morreale, Stephen J.; Nel, Ronel; Paladino, Frank V.

    2016-01-01

    Previous studies have shown that the world’s largest reptile – the leatherback turtle Dermochelys coriacea – conducts flexible foraging migrations that can cover thousands of kilometres between nesting sites and distant foraging areas. The vast distances that may be travelled by migrating leatherback turtles have greatly complicated conservation efforts for this species worldwide. However, we demonstrate, using a combination of satellite telemetry and stable isotope analysis, that approximately half of the nesting leatherbacks from an important rookery in South Africa do not migrate to distant foraging areas, but rather, forage in the coastal waters of the nearby Mozambique Channel. Moreover, this coastal cohort appears to remain resident year-round in shallow waters (turtles Caretta caretta. The rare presence of a resident coastal aggregation of leatherback turtles not only presents a unique opportunity for conservation, but alongside the presence of loggerhead turtles and other endangered marine megafauna in the Mozambique Channel, highlights the importance of this area as a marine biodiversity hotspot. PMID:27886262

  12. HOTSPOT, Field Evaluation of Radiation Release from Nuclear Accident

    International Nuclear Information System (INIS)

    2001-01-01

    1 - Description of program or function: The HOTSPOT Health Physics codes were created to provide Health Physics personnel with a fast, field-portable calculational tool for evaluating accidents involving radioactive materials. HOTSPOT codes are a first-order approximation of the radiation effects associated with the atmospheric release of radioactive materials. HOTSPOT programs are reasonably accurate for a timely initial assessment. More importantly, HOTSPOT codes produce a consistent output for the same input assumptions and minimize the probability of errors associated with reading a graph incorrectly or scaling a universal nomogram during an emergency. Four general programs, PLUME, EXPLOSION, FIRE, and RESUSPENSION, calculate a downwind assessment following the release of radioactive material resulting from a continuous or puff release, explosive release, fuel fire, or an area contamination event. Other programs deal with the release of plutonium, uranium, and tritium to expedite an initial assessment of accidents involving nuclear weapons. Additional programs estimate the dose commitment from inhalation of any one of the radionuclides listed in the database of radionuclides, calibrate a radiation survey instrument for ground survey measurements, and screening of plutonium uptake in the lung. The HOTSPOT codes are fast, portable, easy to use, and fully documented. HOTSPOT supports color high resolution monitors and printers for concentration plots and contours. The codes have been extensively used by the DOS community since 1985. Version 8 allows users to add their own custom radionuclide library and to create custom radionuclide mixtures. It also includes wet deposition to approximate the enhanced plume depletion and ground deposition due to the effects of rain. Additional release geometry options for TRITIUM RELEASE and GENERAL PLUME were added, as well as several other enhancements and improvements. See info (f1) from the main HOTSPOT menu for additional

  13. Implications of salinity pollution hotspots on agricultural production

    Science.gov (United States)

    Floerke, Martina; Fink, Julia; Malsy, Marcus; Voelker, Jeanette; Alcamo, Joseph

    2016-04-01

    , large metropolitan regions are initially loading hotspots and pollution, too, and prevention becomes important as point sources are dependent on sewer connection rates and treatment levels. In conclusion, this study provides a detailed picture of the spatial and temporal distribution of salinity pollution and identifies hotspot areas as well as the dominant sources. Furthermore, impacts of water quality degradation on agricultural production and food security are quantified, which aim for a better understanding of the risks for food security caused by water quality impairment.

  14. Metazoan parasite species richness in Neotropical fishes: hotspots and the geography of biodiversity.

    Science.gov (United States)

    Luque, J L; Poulin, R

    2007-06-01

    Although research on parasite biodiversity has intensified recently, there are signs that parasites remain an underestimated component of total biodiversity in many regions of the planet. To identify geographical hotspots of parasite diversity, we performed qualitative and quantitative analyses of the parasite-host associations in fishes from Latin America and the Caribbean, a region that includes known hotspots of plant and animal biodiversity. The database included 10,904 metazoan parasite-host associations involving 1660 fish species. The number of host species with at least 1 parasite record was less than 10% of the total known fish species in the majority of countries. Associations involving adult endoparasites in actinopterygian fish hosts dominated the database. Across the whole region, no significant difference in parasite species richness was detected between marine and freshwater fishes. As a rule, host body size and study effort (number of studies per fish species) were good predictors of parasite species richness. Some interesting patterns emerged when we included only the regions with highest fish species biodiversity and study effort (Brazil, Mexico and the Caribbean Islands). Independently of differences in study effort or host body sizes, Mexico stands out as a hotspot of parasite diversity for freshwater fishes, as does Brasil for marine fishes. However, among 57 marine fish species common to all 3 regions, populations from the Caribbean consistently harboured more parasite species. These differences may reflect true biological patterns, or regional discrepancies in study effort and local priorities for fish parasitology research.

  15. Identification of coding and non-coding mutational hotspots in cancer genomes.

    Science.gov (United States)

    Piraino, Scott W; Furney, Simon J

    2017-01-05

    The identification of mutations that play a causal role in tumour development, so called "driver" mutations, is of critical importance for understanding how cancers form and how they might be treated. Several large cancer sequencing projects have identified genes that are recurrently mutated in cancer patients, suggesting a role in tumourigenesis. While the landscape of coding drivers has been extensively studied and many of the most prominent driver genes are well characterised, comparatively less is known about the role of mutations in the non-coding regions of the genome in cancer development. The continuing fall in genome sequencing costs has resulted in a concomitant increase in the number of cancer whole genome sequences being produced, facilitating systematic interrogation of both the coding and non-coding regions of cancer genomes. To examine the mutational landscapes of tumour genomes we have developed a novel method to identify mutational hotspots in tumour genomes using both mutational data and information on evolutionary conservation. We have applied our methodology to over 1300 whole cancer genomes and show that it identifies prominent coding and non-coding regions that are known or highly suspected to play a role in cancer. Importantly, we applied our method to the entire genome, rather than relying on predefined annotations (e.g. promoter regions) and we highlight recurrently mutated regions that may have resulted from increased exposure to mutational processes rather than selection, some of which have been identified previously as targets of selection. Finally, we implicate several pan-cancer and cancer-specific candidate non-coding regions, which could be involved in tumourigenesis. We have developed a framework to identify mutational hotspots in cancer genomes, which is applicable to the entire genome. This framework identifies known and novel coding and non-coding mutional hotspots and can be used to differentiate candidate driver regions from

  16. Conservation planning in agricultural landscapes: hotspots of conflict between agriculture and nature.

    Science.gov (United States)

    Shackelford, Gorm E; Steward, Peter R; German, Richard N; Sait, Steven M; Benton, Tim G

    2015-03-01

    Conservation conflict takes place where food production imposes a cost on wildlife conservation and vice versa. Where does conservation impose the maximum cost on production, by opposing the intensification and expansion of farmland? Where does conservation confer the maximum benefit on wildlife, by buffering and connecting protected areas with a habitable and permeable matrix of crop and non-crop habitat? Our aim was to map the costs and benefits of conservation versus production and thus to propose a conceptual framework for systematic conservation planning in agricultural landscapes. World-wide. To quantify these costs and benefits, we used a geographic information system to sample the cropland of the world and map the proportion of non-crop habitat surrounding the cropland, the number of threatened vertebrates with potential to live in or move through the matrix and the yield gap of the cropland. We defined the potential for different types of conservation conflict in terms of interactions between habitat and yield (potential for expansion, intensification, both or neither). We used spatial scan statistics to find 'hotspots' of conservation conflict. All of the 'hottest' hotspots of conservation conflict were in sub-Saharan Africa, which could have impacts on sustainable intensification in this region. Systematic conservation planning could and should be used to identify hotspots of conservation conflict in agricultural landscapes, at multiple scales. The debate between 'land sharing' (extensive agriculture that is wildlife friendly) and 'land sparing' (intensive agriculture that is less wildlife friendly but also less extensive) could be resolved if sharing and sparing were used as different types of tool for resolving different types of conservation conflict (buffering and connecting protected areas by maintaining matrix quality, in different types of matrix). Therefore, both sharing and sparing should be prioritized in hotspots of conflict, in the context of

  17. Mapping publication status and exploring hotspots in a research field: chronic disease self-management.

    Science.gov (United States)

    Lu, Yang; Li, Zheng; Arthur, David

    2014-08-01

    To provide insight into the characteristics of chronic disease self-management by mapping publication status and exploring hotspots. Chronic disease is becoming a major public health issue worldwide, highlighting the importance of self-management in this area. Despite the volume and variety of publications, little is known about how 'chronic disease self-management' has developed, since the first publication 40 years ago. Such is the number of publications in the area, that there is a need for a systematic bibliographic examination to enable clinicians and researchers to navigate this literature. A bibliometric analysis of publications was used. Publication status was achieved using BICOMB software, whereas hotspots were identified with Ucinet software. A search of PubMed was conducted for papers published between 1971-2012. By 2011, the number of publications reached 696, a fourfold increase from the previous 10 years, of which 75% came from the USA and UK. There were 1284 journals, which published chronic disease self-management research, involving various disciplines. The research hotspots highlighted various self-management strategies for the following: diabetes; cardiac vascular and pulmonary chronic disease; pain relief for neoplasms; and obesity. Psychological adjustment was a permeating theme in self-management processes as was using internet-based interventions. Self-management in chronic disease publication has been most evident in developed countries. The bibliographic mapping and identification of publication hotspots provides scholars and practitioners with key target journals, as well as a rigorous overview of the field for use in further research, evidence-based practice and health policy development. © 2014 John Wiley & Sons Ltd.

  18. Exploring spatial patterns and hotspots of diarrhea in Chiang Mai, Thailand

    Directory of Open Access Journals (Sweden)

    Tripathi Nitin K

    2009-06-01

    Full Text Available Abstract Background Diarrhea is a major public health problem in Thailand. The Ministry of Public Health, Thailand, has been trying to monitor and control this disease for many years. The methodology and the results from this study could be useful for public health officers to develop a system to monitor and prevent diarrhea outbreaks. Methods The objective of this study was to analyse the epidemic outbreak patterns of diarrhea in Chiang Mai province, Northern Thailand, in terms of their geographical distributions and hotspot identification. The data of patients with diarrhea at village level and the 2001–2006 population censuses were collected to achieve the objective. Spatial analysis, using geographic information systems (GIS and other methods, was used to uncover the hidden phenomena from the data. In the data analysis section, spatial statistics such as quadrant analysis (QA, nearest neighbour analysis (NNA, and spatial autocorrelation analysis (SAA, were used to identify the spatial patterns of diarrhea in Chiang Mai province. In addition, local indicators of spatial association (LISA and kernel density (KD estimation were used to detect diarrhea hotspots using data at village level. Results The hotspot maps produced by the LISA and KD techniques showed spatial trend patterns of diarrhea diffusion. Villages in the middle and northern regions revealed higher incidences. Also, the spatial patterns of diarrhea during the years 2001 and 2006 were found to represent spatially clustered patterns, both at global and local scales. Conclusion Spatial analysis methods in GIS revealed the spatial patterns and hotspots of diarrhea in Chiang Mai province from the year 2001 to 2006. To implement specific and geographically appropriate public health risk-reduction programs, the use of such spatial analysis tools may become an integral component in the epidemiologic description, analysis, and risk assessment of diarrhea.

  19. Global hotspots of river erosion under global warming

    Science.gov (United States)

    Plink-Bjorklund, P.; Reichler, T.

    2017-12-01

    Extreme precipitation plays a significant role for river hydrology, flood hazards and landscape response. For example, the September 2013 rainstorm in the Colorado Front Range evacuated the equivalent of hundreds to thousands of years of hillslope weathering products. Although promoted by steep topography, the Colorado event is clearly linked to rainfall intensity, since most of the 1100 debris flows occurred within the highest rainfall contour. Additional evidence for a strong link between extreme precipitation and river erosion comes from the sedimentary record, and especially from that of past greenhouse climates. The existence of such a link suggests that information about global rainfall patterns can be used to define regions of increased erosion potential. However, the question arises what rainfall criteria to use and how well the method works. A related question is how ongoing climate change and the corresponding shifts in rainfall might impact the results. Here, we use atmospheric reanalysis and output from a climate model to identify regions that are particularly susceptible to landscape change in response to extreme precipitation. In order to define the regions, we combine several hydroclimatological and geomorphological criteria into a single index of erosion potential. We show that for current climate, our criteria applied to atmospheric reanalysis or to climate model data successfully localize known areas of increased erosion potential, such as the Colorado region. We then apply our criteria to climate model data for future climate to document how the location, extent, and intensity of erosion hotspots are likely to change under global warming.

  20. Incorporating evolutionary history into conservation planning in biodiversity hotspots.

    Science.gov (United States)

    Buerki, Sven; Callmander, Martin W; Bachman, Steven; Moat, Justin; Labat, Jean-Noël; Forest, Félix

    2015-02-19

    There is increased evidence that incorporating evolutionary history directly in conservation actions is beneficial, particularly given the likelihood that extinction is not random and that phylogenetic diversity (PD) is lost at higher rates than species diversity. This evidence is even more compelling in biodiversity hotspots, such as Madagascar, where less than 10% of the original vegetation remains. Here, we use the Leguminosae, an ecologically and economically important plant family, and a combination of phylogenetics and species distribution modelling, to assess biodiversity patterns and identify regions, coevolutionary processes and ecological factors that are important in shaping this diversity, especially during the Quaternary. We show evidence that species distribution and community PD are predicted by watershed boundaries, which enable the identification of a network of refugia and dispersal corridors that were perhaps important for maintaining community integrity during past climate change. Phylogenetically clustered communities are found in the southwest of the island at low elevation and share a suite of morphological characters (especially fruit morphology) indicative of coevolution with their main dispersers, the extinct and extant lemurs. Phylogenetically over-dispersed communities are found along the eastern coast at sea level and may have resulted from many independent dispersal events from the drier and more seasonal regions of Madagascar. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  1. Isotopic identification of nitrogen hotspots across natural terrestrial ecosystems

    Directory of Open Access Journals (Sweden)

    E. Bai

    2012-08-01

    Full Text Available Nitrogen (N influences local biological processes, ecosystem productivity, the composition of the atmospheric-climate system, and the human endeavour as a whole. Here we use natural variations in N isotopes, coupled with two models, to trace global pathways of N loss from the land to the water and atmosphere. We show that denitrification accounts for approximately 35 % of total N losses from the natural soil, with NO, N2O, and N2 fluxes equal to 15.7 ± 4.7 Tg N yr−1, 10.2 ± 3.0 Tg N yr−1, and 21.0 ± 6.1 Tg N yr−1, respectively. Our analysis points to tropical regions as the major "hotspot" of nitrogen export from the terrestrial biosphere, accounting for 71 % of global N losses from the natural land surface. The poorly studied Congo Basin is further identified as one of the major natural sources of atmospheric N2O. Extra-tropical areas, by contrast, lose a greater fraction of N via leaching pathways (~77 % of total N losses than do tropical biomes, likely contributing to N limitations of CO2 uptake at higher latitudes. Our results provide an independent constraint on global models of the N cycle among different regions of the unfertilized biosphere.

  2. Atmospheric gravity waves in the Red Sea: a new hotspot

    KAUST Repository

    Magalhaes, J. M.

    2011-02-03

    The region of the Middle East around the Red Sea (between 32° E and 44° E longitude and 12° N and 28° N latitude) is a currently undocumented hotspot for atmospheric gravity waves (AGWs). Satellite imagery shows evidence that this region is prone to relatively high occurrence of AGWs compared to other areas in the world, and reveals the spatial characteristics of these waves. The favorable conditions for wave propagation in this region are illustrated with three typical cases of AGWs propagating in the lower troposphere over the sea. Using weakly nonlinear long wave theory and the observed characteristic wavelengths we obtain phase speeds which are consistent with those observed and typical for AGWs, with the Korteweg-de Vries theory performing slightly better than Benjamin-Davis-Acrivos-Ono theory as far as phase speeds are concerned. ERS-SAR and Envisat-ASAR satellite data analysis between 1993 and 2008 reveals signatures consistent with horizontally propagating large-scale internal waves. These signatures cover the entire Red Sea and are more frequently observed between April and September, although they also occur during the rest of the year. The region\\'s (seasonal) propagation conditions for AGWs, based upon average vertical atmospheric stratification profiles suggest that many of the signatures identified in the satellite images are atmospheric internal waves. © Author(s) 2011.

  3. Hotspot-mediated non-dissipative and ultrafast plasmon passage

    Science.gov (United States)

    Roller, Eva-Maria; Besteiro, Lucas V.; Pupp, Claudia; Khorashad, Larousse Khosravi; Govorov, Alexander O.; Liedl, Tim

    2017-08-01

    Plasmonic nanoparticles hold great promise as photon handling elements and as channels for coherent transfer of energy and information in future all-optical computing devices. Coherent energy oscillations between two spatially separated plasmonic entities via a virtual middle state exemplify electron-based population transfer, but their realization requires precise nanoscale positioning of heterogeneous particles. Here, we show the assembly and optical analysis of a triple-particle system consisting of two gold nanoparticles with an inter-spaced silver island. We observe strong plasmonic coupling between the spatially separated gold particles, mediated by the connecting silver particle, with almost no dissipation of energy. As the excitation energy of the silver island exceeds that of the gold particles, only quasi-occupation of the silver transfer channel is possible. We describe this effect both with exact classical electrodynamic modelling and qualitative quantum-mechanical calculations. We identify the formation of strong hotspots between all particles as the main mechanism for the lossless coupling and thus coherent ultrafast energy transfer between the remote partners. Our findings could prove useful for quantum gate operations, as well as for classical charge and information transfer processes.

  4. N2O emission hotspots at different spatial scales and governing factors for small scale hotspots

    International Nuclear Information System (INIS)

    Heuvel, R.N. van den; Hefting, M.M.; Tan, N.C.G.; Jetten, M.S.M.; Verhoeven, J.T.A.

    2009-01-01

    Chronically nitrate-loaded riparian buffer zones show high N 2 O emissions. Often, a large part of the N 2 O is emitted from small surface areas, resulting in high spatial variability in these buffer zones. These small surface areas with high N 2 O emissions (hotspots) need to be investigated to generate knowledge on the factors governing N 2 O emissions. In this study the N 2 O emission variability was investigated at different spatial scales. Therefore N 2 O emissions from three 32 m 2 grids were determined in summer and winter. Spatial variation and total emission were determined on three different scales (0.3 m 2 , 0.018 m 2 and 0.0013 m 2 ) at plots with different levels of N 2 O emissions. Spatial variation was high at all scales determined and highest at the smallest scale. To test possible factors inducing small scale hotspots, soil samples were collected for slurry incubation to determine responses to increased electron donor/acceptor availability. Acetate addition did increase N 2 O production, but nitrate addition failed to increase total denitrification or net N 2 O production. N 2 O production was similar in all soil slurries, independent of their origin from high or low emission soils, indicating that environmental conditions (including physical factors like gas diffusion) rather than microbial community composition governed N 2 O emission rates

  5. Cancer associated epigenetic transitions identified by genome-wide histone methylation binding profiles in human colorectal cancer samples and paired normal mucosa

    International Nuclear Information System (INIS)

    Enroth, Stefan; Rada-Iglesisas, Alvaro; Andersson, Robin; Wallerman, Ola; Wanders, Alkwin; Påhlman, Lars; Komorowski, Jan; Wadelius, Claes

    2011-01-01

    Despite their well-established functional roles, histone modifications have received less attention than DNA methylation in the cancer field. In order to evaluate their importance in colorectal cancer (CRC), we generated the first genome-wide histone modification profiles in paired normal colon mucosa and tumor samples. Chromatin immunoprecipitation and microarray hybridization (ChIP-chip) was used to identify promoters enriched for histone H3 trimethylated on lysine 4 (H3K4me3) and lysine 27 (H3K27me3) in paired normal colon mucosa and tumor samples from two CRC patients and for the CRC cell line HT29. By comparing histone modification patterns in normal mucosa and tumors, we found that alterations predicted to have major functional consequences were quite rare. Furthermore, when normal or tumor tissue samples were compared to HT29, high similarities were observed for H3K4me3. However, the differences found for H3K27me3, which is important in determining cellular identity, indicates that cell lines do not represent optimal tissue models. Finally, using public expression data, we uncovered previously unknown changes in CRC expression patterns. Genes positive for H3K4me3 in normal and/or tumor samples, which are typically already active in normal mucosa, became hyperactivated in tumors, while genes with H3K27me3 in normal and/or tumor samples and which are expressed at low levels in normal mucosa, became hypersilenced in tumors. Genome wide histone modification profiles can be used to find epigenetic aberrations in genes associated with cancer. This strategy gives further insights into the epigenetic contribution to the oncogenic process and may identify new biomarkers

  6. Juniper Pollen Hotspots in the Southwest

    Science.gov (United States)

    Bunderson, L. D.; VandeWater, P.; Luvall, J.; Levetin, E.

    2013-01-01

    Rationale: Juniperus pollen is a major allergen in Texas, Oklahoma, and New Mexico. While the bulk of pollen may be released in rural areas, large amounts of pollen can be transported to urban areas. Major juniper species in the region include: Juniperus ashei, J. virginiana, J. pinchotii, and J. monosperma. Pollen release is virtually continuous beginning in late September with J. pinchotii and ending in May with J. monosperma. Urban areas in the region were evaluated for the potential of overlapping seasons in order to inform sensitive individuals. Methods: Burkard volumetric pollen traps were established for two consecutive spring seasons at 6 sites in northern New Mexico and 6 sites for two consecutive winter and fall seasons in Texas and Oklahoma Standard methods were used in the preparation and analysis of slides. Results: The Dallas-Fort Worth Metroplex is home to over 6 million people. It is adjacent to populations of J. pinchotii, J. virginiana, and J. ashei. Peak concentration near Dallas for J. ashei in 2011 was 5891 pollen grains/m3 in January 7th. The peak date for J. pinchotii at an upwind sampling location in San Marcos, TX was November 1, 2010 and peak for J. virginiana at a nearby station in Tulsa, OK was November 1, 2010 and peak for J. virginiana at a nearby station in Tulsa, OK was February 20, 2011. Amarillo, TX is adjacent to J. pinchotii, J. ashei, and J. monosperma populations and may be subject to juniper pollen from September through May. Conclusions: Considering the overlapping distributions of juniper trees and the overlapping temporal release of pollen, sensitive patients may benefit from avoiding hotspots.

  7. Hotspots on Io During the Ganymede 2 Encounter

    Science.gov (United States)

    1996-01-01

    The Near Infrared Mapping Spectrometer (NIMS) on the Galileo spacecraft imaged Io at high spectral resolution at a range of 439,000 km (275,000 miles) during the G2 encounter on 6 September 1996. This image shows, on the right, Io as seen by NIMS, centered on 150 W longitude. The image on the left shows the same view point from Voyager data (from the encounters in 1979 and 1980). The NIMS image can be compared to the NIMS hotspot image from the G1 orbit (June 1996) to monitor changes on Io. The most dramatic feature of the G2 image is the hotspot at Malik Patera. Preliminary analysis of the data yields a temperature of at least 1000 K (727 C) for this hotspot, an increase of more than 300 K from the G1 encounter. In the overlap area of the G1 and G2 images all the hotspots seen during the G1 encounter are also seen in the G2 image. Other hotspots were seen, including one at the Pele plume origin site. This image is at the 4 micron band to best view the Malik hotspot. Most of the other hotspots are best seen at longer wavelengths. NIMS is continuing to observe Io to monitor volcanic activity throughout the Galileo mission.The Jet Propulsion Laboratory, Pasadena, CA manages the mission for NASA's Office of Space Science, Washington, DC.This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://galileo.jpl.nasa.gov.

  8. Potential geographic "hotspots" for drug-injection related transmission of HIV and HCV and for initiation into injecting drug use in New York City, 2011-2015, with implications for the current opioid epidemic in the US.

    Science.gov (United States)

    Des Jarlais, D C; Cooper, H L F; Arasteh, K; Feelemyer, J; McKnight, C; Ross, Z

    2018-01-01

    We identified potential geographic "hotspots" for drug-injecting transmission of HIV and hepatitis C virus (HCV) among persons who inject drugs (PWID) in New York City. The HIV epidemic among PWID is currently in an "end of the epidemic" stage, while HCV is in a continuing, high prevalence (> 50%) stage. We recruited 910 PWID entering Mount Sinai Beth Israel substance use treatment programs from 2011-2015. Structured interviews and HIV/ HCV testing were conducted. Residential ZIP codes were used as geographic units of analysis. Potential "hotspots" for HIV and HCV transmission were defined as 1) having relatively large numbers of PWID 2) having 2 or more HIV (or HCV) seropositive PWID reporting transmission risk-passing on used syringes to others, and 3) having 2 or more HIV (or HCV) seronegative PWID reporting acquisition risk-injecting with previously used needles/syringes. Hotspots for injecting drug use initiation were defined as ZIP codes with 5 or more persons who began injecting within the previous 6 years. Among PWID, 96% injected heroin, 81% male, 34% White, 15% African-American, 47% Latinx, mean age 40 (SD = 10), 7% HIV seropositive, 62% HCV seropositive. Participants resided in 234 ZIP codes. No ZIP codes were identified as potential hotspots due to small numbers of HIV seropositive PWID reporting transmission risk. Four ZIP codes were identified as potential hotspots for HCV transmission. 12 ZIP codes identified as hotspots for injecting drug use initiation. For HIV, the lack of potential hotspots is further validation of widespread effectiveness of efforts to reduce injecting-related HIV transmission. Injecting-related HIV transmission is likely to be a rare, random event. HCV prevention efforts should include focus on potential hotspots for transmission and on hotspots for initiation into injecting drug use. We consider application of methods for the current opioid epidemic in the US.

  9. The silent mass extinction of insect herbivores in biodiversity hotspots.

    Science.gov (United States)

    Fonseca, Carlos Roberto

    2009-12-01

    Habitat loss is silently leading numerous insects to extinction. Conservation efforts, however, have not been designed specifically to protect these organisms, despite their ecological and evolutionary significance. On the basis of species-host area equations, parameterized with data from the literature and interviews with botanical experts, I estimated the number of specialized plant-feeding insects (i.e., monophages) that live in 34 biodiversity hotspots and the number committed to extinction because of habitat loss. I estimated that 795,971-1,602,423 monophagous insect species live in biodiversity hotspots on 150,371 endemic plant species, which is 5.3-10.6 monophages per plant species. I calculated that 213,830-547,500 monophagous species are committed to extinction in biodiversity hotspots because of reduction of the geographic range size of their endemic hosts. I provided rankings of biodiversity hotspots on the basis of estimated richness of monophagous insects and on estimated number of extinctions of monophagous species. Extinction rates were predicted to be higher in biodiversity hotspots located along strong environmental gradients and on archipelagos, where high spatial turnover of monophagous species along the geographic distribution of their endemic plants is likely. The results strongly support the overall strategy of selecting priority conservation areas worldwide primarily on the basis of richness of endemic plants. To face the global decline of insect herbivores, one must expand the coverage of the network of protected areas and improve the richness of native plants on private lands.

  10. Global warming and extinctions of endemic species from biodiversity hotspots.

    Science.gov (United States)

    Malcolm, Jay R; Liu, Canran; Neilson, Ronald P; Hansen, Lara; Hannah, Lee

    2006-04-01

    Global warming is a key threat to biodiversity, but few researchers have assessed the magnitude of this threat at the global scale. We used major vegetation types (biomes) as proxies for natural habitats and, based on projected future biome distributions under doubled-CO2 climates, calculated changes in habitat areas and associated extinctions of endemic plant and vertebrate species in biodiversity hotspots. Because of numerous uncertainties in this approach, we undertook a sensitivity analysis of multiple factors that included (1) two global vegetation models, (2) different numbers of biome classes in our biome classification schemes, (3) different assumptions about whether species distributions were biome specific or not, and (4) different migration capabilities. Extinctions were calculated using both species-area and endemic-area relationships. In addition, average required migration rates were calculated for each hotspot assuming a doubled-CO2 climate in 100 years. Projected percent extinctions ranged from hotspots were the Cape Floristic Region, Caribbean, Indo-Burma, Mediterranean Basin, Southwest Australia, and Tropical Andes, where plant extinctions per hotspot sometimes exceeded 2000 species. Under the assumption that projected habitat changes were attained in 100 years, estimated global-warming-induced rates of species extinctions in tropical hotspots in some cases exceeded those due to deforestation, supporting suggestions that global warming is one of the most serious threats to the planet's biodiversity.

  11. Arago Seamount: The missing hotspot found in the Austral Islands

    Science.gov (United States)

    Bonneville, Alain; Le Suavé, Raymond; Audin, Laurence; Clouard, Valérie; Dosso, Laure; Yves Gillot, Pierre; Janney, Philip; Jordahl, Kelsey; Maamaatuaiahutapu, Keitapu

    2002-11-01

    The Austral archipelago, on the western side of the South Pacific superswell, is composed of several volcanic chains, corresponding to distinct events from 35 Ma to the present, and lies on oceanic crust created between 60 and 85 Ma. In 1982, Turner and Jarrard proposed that the two distinct volcanic stages found on Rurutu Island and dated as 12 Ma and 1 Ma could be due to two different hotspots, but no evidence of any recent aerial or submarine volcanic source has ever been found. In July 1999, expedition ZEPOLYF2 aboard the R/V L'Atalante conducted a geophysical survey of the northern part of the Austral volcanic archipelago. Thirty seamounts were mapped for the first time, including a very shallow one (French Navy ship that discovered its summit in 1993, is the missing hotspot in the Cook-Austral history. This interpretation adds a new hotspot to the already complicated geologic history of this region. We suggest that several hotspots have been active simultaneously on a region of the seafloor that does not exceed 2000 km in diameter and that each of them had a short lifetime (<20 m.y.). These short-lived and closely spaced hotspots cannot be the result of discrete deep-mantle plumes and are likely due to more local upwelling in the upper mantle strongly influenced by weaknesses in the lithosphere.

  12. Thermally-Driven Mantle Plumes Reconcile Hot-spot Observations

    Science.gov (United States)

    Davies, D.; Davies, J.

    2008-12-01

    Hot-spots are anomalous regions of magmatism that cannot be directly associated with plate tectonic processes (e.g. Morgan, 1972). They are widely regarded as the surface expression of upwelling mantle plumes. Hot-spots exhibit variable life-spans, magmatic productivity and fixity (e.g. Ito and van Keken, 2007). This suggests that a wide-range of upwelling structures coexist within Earth's mantle, a view supported by geochemical and seismic evidence, but, thus far, not reproduced by numerical models. Here, results from a new, global, 3-D spherical, mantle convection model are presented, which better reconcile hot-spot observations, the key modification from previous models being increased convective vigor. Model upwellings show broad-ranging dynamics; some drift slowly, while others are more mobile, displaying variable life-spans, intensities and migration velocities. Such behavior is consistent with hot-spot observations, indicating that the mantle must be simulated at the correct vigor and in the appropriate geometry to reproduce Earth-like dynamics. Thermally-driven mantle plumes can explain the principal features of hot-spot volcanism on Earth.

  13. Mantle Convection beneath the Aegir Ridge, a Shadow in the Iceland Hotspot

    Science.gov (United States)

    Howell, S. M.; Ito, G.; Breivik, A. J.; Hanan, B. B.; Mjelde, R.; Sayit, K.; Vogt, P. R.

    2012-12-01

    The Iceland Hotspot has produced extensive volcanism spanning much of the ocean basin between Greenland and Norway, forming one of the world's largest igneous provinces. However, an apparent igneous "shadow" in hotspot activity is located at the fossil Aegir Ridge, which formed anomalously thin crust, despite this ridge being near the Iceland hotspot when it was active. The Aegir Ridge accommodated seafloor spreading northeast of present-day Iceland from the time of continental breakup at ~55 Ma until ~25 Ma, at which point spreading shifted west to the Kolbeinsey Ridge. To address the cause of the anomalously thin crust produced by the Aegir Ridge, we use three-dimensional numerical models to simulate the interaction between a mantle plume beneath the Iceland hotspot, rifting continental lithosphere, and the time-evolving North Atlantic ridge system. Two end-member hypotheses were investigated: (1) Material emanating from the Iceland mantle plume was blocked from reaching the Aegir Ridge by the thick lithosphere of the Jan Mayen Microcontinent as the Kolbeinsey Ridge began rifting it from Greenland at ~30 Ma, just east of the plume center; (2) Plume material was not blocked and did reach the Aegir Ridge, but had already experienced partial melting closer to the hotspot. This material was then unable to produce melt volumes at the Aegir Ridge comparable to those of pristine mantle. To test these hypotheses, we vary the volume flux and viscosity of the plume, and identify which conditions do and do not lead to the Aegir Ridge forming anomalously thin crust. Results show that the combination of plume material being drawn into the lithospheric channels beneath the Reykjanes Ridge and Kolbeinsey Ridge after their respective openings, and the impedance of plume flow by the Jan Mayen Microcontinent (hypothesis 1), can deprive the Aegir Ridge of plume influence. This leads to low crustal thicknesses that are comparable to those observed. We have yet to produce a model

  14. Random mutagenesis of the nucleotide-binding domain of NRC1 (NB-LRR Required for Hypersensitive Response-Associated Cell Death-1), a downstream signalling nucleotide-binding, leucine-rich repeat (NB-LRR) protein, identifies gain-of-function mutations in the nucleotide-binding pocket

    NARCIS (Netherlands)

    Sueldo, D.J.; Shimels, M.Z.; Spiridon, L.N.; Caldararu, O.; Petrescu, A.J.; Joosten, M.H.A.J.; Tameling, W.I.L.

    2015-01-01

    •Plant nucleotide-binding, leucine-rich repeat (NB-LRR) proteins confer immunity to pathogens possessing the corresponding avirulence proteins. Activation of NB-LRR proteins is often associated with induction of the hypersensitive response (HR), a form of programmed cell death. •NRC1 (NB-LRR

  15. Prdm9 controls activation of mammalian recombination hotspots.

    Science.gov (United States)

    Parvanov, Emil D; Petkov, Petko M; Paigen, Kenneth

    2010-02-12

    Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, ensures the orderly segregation of meiotic chromosomes and creates genetic variation among offspring. A locus on mouse chromosome 17, which controls activation of recombination at multiple distant hotspots, has been mapped within a 181-kilobase interval, three of whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone H3K4 trimethylase that is expressed in early meiosis and whose deficiency results in sterility in both sexes. Mus musculus exhibits five alleles of Prdm9; human populations exhibit two predominant alleles and multiple minor alleles. The identification of Prdm9 as a protein regulating mammalian recombination hotspots initiates molecular studies of this important biological control system.

  16. Interventions to reduce suicides at suicide hotspots: a systematic review.

    Science.gov (United States)

    Cox, Georgina R; Owens, Christabel; Robinson, Jo; Nicholas, Angela; Lockley, Anne; Williamson, Michelle; Cheung, Yee Tak Derek; Pirkis, Jane

    2013-03-09

    'Suicide hotspots' include tall structures (for example, bridges and cliffs), railway tracks, and isolated locations (for example, rural car parks) which offer direct means for suicide or seclusion that prevents intervention. We searched Medline for studies that could inform the following question: 'What interventions are available to reduce suicides at hotspots, and are they effective?' There are four main approaches: (a) restricting access to means (through installation of physical barriers); (b) encouraging help-seeking (by placement of signs and telephones); (c) increasing the likelihood of intervention by a third party (through surveillance and staff training); and (d) encouraging responsible media reporting of suicide (through guidelines for journalists). There is relatively strong evidence that reducing access to means can avert suicides at hotspots without substitution effects. The evidence is weaker for the other approaches, although they show promise. More well-designed intervention studies are needed to strengthen this evidence base.

  17. Exploring the influence of EGCG on the β-sheet-rich oligomers of human islet amyloid polypeptide (hIAPP1-37 and identifying its possible binding sites from molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    Qianqian Wang

    Full Text Available EGCG possesses the ability of disaggregating the existing amyloid fibrils which were associated with many age-related degenerative diseases. However, the molecular mechanism of EGCG to disaggregate these fibrils is poorly known. In this work, to study the influence of EGCG on the full-length human islet amyloid polypeptide 1-37 (hIAPP1-37 oligomers, molecular dynamics simulations of hIAPP1-37 pentamer and decamer with EGCG were performed, respectively. The obtained results indicate that EGCG indeed destabilized the hIAPP1-37 oligomers. The nematic order parameter and secondary structure calculations coupled with the free-energy landscape indicate that EGCG broke the initial ordered pattern of two polymers, greatly reduced their β-sheet content and enlarged their conformational space. On this basis, three possible target sites were identified with the binding capacity order of S1>S2>S3. After a deeper analysis of each site, we found that S1 was the most possible site on which residues B-Ile26/Ala25, A-Phe23, B/C-Leu27 and E-Tyr37 played an important role for their binding. The proposal of this molecular mechanism can not only provide a prospective interaction figure between EGCG and β-sheet-rich fibrils of hIAPP1-37, but also is useful for further discovering other potential inhibitors.

  18. Acetylated Histone H3K9 is associated with meiotic recombination hotspots, and plays a role in recombination redundantly with other factors including the H3K4 methylase Set1 in fission yeast

    Science.gov (United States)

    Yamada, Shintaro; Ohta, Kunihiro; Yamada, Takatomi

    2013-01-01

    Histone modifications are associated with meiotic recombination hotspots, discrete sites with augmented recombination frequency. For example, trimethylation of histone H3 lysine4 (H3K4me3) marks most hotspots in budding yeast and mouse. Modified histones are known to regulate meiotic recombination partly by promoting DNA double-strand break (DSB) formation at hotspots, but the role and precise landscape of involved modifications remain unclear. Here, we studied hotspot-associated modifications in fission yeast and found general features: acetylation of H3 lysine9 (H3K9ac) is elevated, and H3K4me3 is not significantly enriched. Mutating H3K9 to non-acetylatable alanine mildly reduced levels of the DSB-inducing protein Rec12 (the fission yeast homologue of Spo11) and DSB at hotspots, indicating that H3K9ac may be involved in DSB formation by enhancing the interaction between Rec12 and hotspots. In addition, we found that the lack of the H3K4 methyltransferase Set1 generally increased Rec12 binding to chromatin but partially reduced DSB formation at some loci, suggesting that Set1 is also involved in DSB formation. These results suggest that meiotic DSB formation is redundantly regulated by multiple chromatin-related factors including H3K9ac and Set1 in fission yeast. PMID:23382177

  19. Energy efficient hotspot-targeted embedded liquid cooling of electronics

    International Nuclear Information System (INIS)

    Sharma, Chander Shekhar; Tiwari, Manish K.; Zimmermann, Severin; Brunschwiler, Thomas; Schlottig, Gerd; Michel, Bruno; Poulikakos, Dimos

    2015-01-01

    Highlights: • We present a novel concept for hotspot-targeted, energy efficient ELC for electronic chips. • Microchannel throttling zones distribute flow optimally without any external control. • Design is optimized for highly non-uniform multicore chip heat flux maps. • Optimized design minimizes chip temperature non-uniformity. • This is achieved with pumping power consumption less than 1% of total chip power. - Abstract: Large data centers today already account for nearly 1.31% of total electricity consumption with cooling responsible for roughly 33% of that energy consumption. This energy intensive cooling problem is exacerbated by the presence of hotspots in multicore microprocessors due to excess coolant flow requirement for thermal management. Here we present a novel liquid-cooling concept, for targeted, energy efficient cooling of hotspots through passively optimized microchannel structures etched into the backside of a chip (embedded liquid cooling or ELC architecture). We adopt an experimentally validated and computationally efficient modeling approach to predict the performance of our hotspot-targeted ELC design. The design is optimized for exemplar non-uniform chip power maps using Response Surface Methodology (RSM). For industrially acceptable limits of approximately 0.4 bar (40 kPa) on pressure drop and one percent of total chip power on pumping power, the optimized designs are computationally evaluated against a base, standard ELC design with uniform channel widths and uniform flow distribution. For an average steady-state heat flux of 150 W/cm 2 in core areas (hotspots) and 20 W/cm 2 over remaining chip area (background), the optimized design reduces the maximum chip temperature non-uniformity by 61% to 3.7 °C. For a higher average, steady-state hotspot heat flux of 300 W/cm 2 , the maximum temperature non-uniformity is reduced by 54% to 8.7 °C. It is shown that the base design requires a prohibitively high level of pumping power (about

  20. Hot-spots of radio sources in clusters of galaxies

    International Nuclear Information System (INIS)

    Saikia, D.J.

    1979-01-01

    A sample of extragalactic double radio sources is examined to test for a correlation between the prominence of compact hot-spots located at their outer edges and membership of clusters of galaxies. To minimize the effects of incompleteness in published catalogues of clusters, cluster classification is based on the number of galaxies in the neighbourhood of each source. After eliminating possible selection effects, it is found that sources in regions of high galactic density tend to have less prominent hot-spots. It is argued that the result is consistent with the 'continuous-flow' models of radio sources, but poses problems for the gravitational slingshot model. (author)

  1. Identification of evolutionary hotspots based on genetic data from multiple terrestrial and aquatic taxa and gap analysis of hotspots in protected lands encompassed by the South Atlantic Landscape Conservation Cooperative.

    Science.gov (United States)

    Robinson, J.; Snider, M.; Duke, J.; Moyer, G.R.

    2014-01-01

     The southeastern United States is a recognized hotspot of biodiversity for a variety of aquatic taxa, including fish, amphibians, and mollusks. Unfortunately, the great diversity of the area is accompanied by a large proportion of species at risk of extinction . Gap analysis was employed to assess the representation of evolutionary hotspots in protected lands w h ere an evolutionary hotspot was defined as an area with high evolutionary potential and measured by atypical patterns of genetic divergence, genetic diversity, and to a lesser extent genetic similarity across multiple terrestrial or aquatic taxa. A survey of the primary literature produced 16 terrestrial and 14 aquatic genetic datasets for estimation of genetic divergence and diversity. Relative genetic diversity and divergence values for each terrestrial and aquatic dataset were used for interpolation of multispecies genetic surfaces and subsequent visualization using ArcGIS. The multispecies surfaces interpolated from relative divergences and diversity data identified numerous evolutionary hotspots for both terrestrial and aquatic taxa , many of which were afforded some current protection. For instance, 14% of the cells identified as hotspots of aquatic diversity were encompassed by currently protected areas. Additionally, 25% of the highest 1% of terrestrial diversity cells were afforded some level of protection. In contrast, areas of high and low divergence among species, and areas of high variance in diversity were poorly represented in the protected lands. Of particular interest were two areas that were consistently identified by several different measures as important from a conservation perspective. These included an area encompassing the panhandle of Florida and southern Georgia near the Apalachicola National Forest (displaying varying levels of genetic divergence and greater than average levels of genetic diversity) and a large portion of the coastal regions of North and South Carolina

  2. Correlates of injecting in an HIV incidence hotspot among substance users in Tijuana, Mexico.

    Science.gov (United States)

    Kori, Nana; Roth, Alexis M; Lozada, Remedios; Vera, Alicia; Brouwer, Kimberly C

    2014-05-01

    Substance use and HIV are growing problems in the Mexico-U.S. border city of Tijuana, a sex tourism destination situated on a northbound drug trafficking route. In a previous longitudinal study of injection drug users (IDUs), we found that >90% of incident HIV cases occurred within an 'HIV incidence hotspot,' consisting of 2.5-blocks. This study examines behavioral, social, and environmental correlates associated with injecting in this HIV hotspot. From 4/06 to 6/07, IDUs aged ≥18 years were recruited using respondent-driven sampling. Participants underwent antibody testing for HIV and syphilis and interviewer-administered surveys eliciting information on demographics, drug use, sexual behaviors, and socio-environmental influences. Participants were defined as injecting in the hotspot if they most frequently injected within a 3 standard deviational ellipse of the cohort's incident HIV cases. Logistic regression was used to identify individual and structural factors associated with the HIV 'hotspot'. Of 1031 IDUs, the median age was 36 years; 85% were male; HIV prevalence was 4%. As bivariate analysis indicated different correlates for males and females, models were stratified by sex. Factors independently associated with injecting in the HIV hotspot for male IDUs included homelessness (AOR 1.72; 95%CI 1.14-2.6), greater intra-urban mobility (AOR 3.26; 95%CI 1.67-6.38), deportation (AOR 1.58; 95%CI 1.18-2.12), active syphilis (AOR 3.03; 95%CI 1.63-5.62), needle sharing (AOR 0.57; 95%CI 0.42-0.78), various police interactions, perceived HIV infection risk (AOR 1.52; 95%CI 1.13-2.03), and health insurance status (AOR 0.53; 95%CI 0.33-0.87). For female IDUs, significant factors included sex work (AOR 8.2; 95%CI 2.2-30.59), lifetime syphilis exposure (AOR 2.73; 95%CI 1.08-6.93), injecting inside (AOR 5.26; 95%CI 1.54-17.92), arrests for sterile syringe possession (AOR 4.87; 95%I 1.56-15.15), prior HIV testing (AOR 2.45; 95%CI 1.04-5.81), and health insurance status

  3. Orchid conservation in the biodiversity hotspot of southwestern China.

    Science.gov (United States)

    Liu, Qiang; Chen, Jin; Corlett, Richard T; Fan, XuLi; Yu, DongLi; Yang, HongPei; Gao, JiangYun

    2015-12-01

    Xishuangbanna is on the northern margins of tropical Asia in southwestern China and has the largest area of tropical forest remaining in the country. It is in the Indo-Burma hotspot and contains 16% of China's vascular flora in biodiversity. To understand the effects of land-use change and collection on orchid species diversity and determine protection priorities, we conducted systematic field surveys, observed markets, interviewed orchid collectors, and then determined the conservation status of all orchids. We identified 426 orchid species in 115 genera in Xishuangbanna: 31% of all orchid species that occur in China. Species richness was highest at 1000-1200 m elevation. Three orchid species were assessed as possibly extinct in the wild, 15 as critically endangered, 82 as endangered, 124 as vulnerable, 186 as least concern, and 16 as data deficient. Declines over 20 years in harvested species suggested over-collection was the major threat, and utility value (i.e., medicinal or ornamental value) was significantly related to endangerment. Expansion of rubber tree plantations was less of a threat to orchids than to other taxa because only 75 orchid species (17.6%) occurred below the 1000-m-elevation ceiling for rubber cultivation, and most of these (46) occurred in nature reserves. However, climate change is projected to lift this ceiling to around 1300 m by 2050, and the limited area at higher elevations reduces the potential for upslope range expansion. The Xishuangbanna Tropical Botanical Garden is committed to achieving zero plant extinctions in Xishuangbanna, and orchids are a high priority. Appropriate in and ex situ conservation strategies, including new protected areas and seed banking, have been developed for every threatened orchid species and are being implemented. © 2015 Society for Conservation Biology.

  4. Multisectoral Climate Impact Hotspots in a Warming World

    Science.gov (United States)

    Piontek, Franziska; Mueller, Christoph; Pugh, Thomas A. M.; Clark, Douglas B.; Deryng, Delphine; Elliott, Joshua; deJesusColonGonzalez, Felipe; Floerke, Martina; Folberth, Christian; Franssen, Wietse; hide

    2014-01-01

    The impacts of global climate change on different aspects of humanity's diverse life-support systems are complex and often difficult to predict. To facilitate policy decisions on mitigation and adaptation strategies, it is necessary to understand, quantify, and synthesize these climate-change impacts, taking into account their uncertainties. Crucial to these decisions is an understanding of how impacts in different sectors overlap, as overlapping impacts increase exposure, lead to interactions of impacts, and are likely to raise adaptation pressure. As a first step we develop herein a framework to study coinciding impacts and identify regional exposure hotspots. This framework can then be used as a starting point for regional case studies on vulnerability and multifaceted adaptation strategies. We consider impacts related to water, agriculture, ecosystems, and malaria at different levels of global warming. Multisectoral overlap starts to be seen robustly at a mean global warming of 3 degC above the 1980-2010 mean, with 11% of the world population subject to severe impacts in at least two of the four impact sectors at 4 degC. Despite these general conclusions, we find that uncertainty arising from the impact models is considerable, and larger than that from the climate models. In a low probability-high impact worst-case assessment, almost the whole inhabited world is at risk for multisectoral pressures. Hence, there is a pressing need for an increased research effort to develop a more comprehensive understanding of impacts, as well as for the development of policy measures under existing uncertainty.

  5. The 1.1 Å resolution structure of a periplasmic phosphate-binding protein from Stenotrophomonas maltophilia: a crystallization contaminant identified by molecular replacement using the entire Protein Data Bank.

    Science.gov (United States)

    Keegan, Ronan; Waterman, David G; Hopper, David J; Coates, Leighton; Taylor, Graham; Guo, Jingxu; Coker, Alun R; Erskine, Peter T; Wood, Steve P; Cooper, Jonathan B

    2016-08-01

    During efforts to crystallize the enzyme 2,4-dihydroxyacetophenone dioxygenase (DAD) from Alcaligenes sp. 4HAP, a small number of strongly diffracting protein crystals were obtained after two years of crystal growth in one condition. The crystals diffracted synchrotron radiation to almost 1.0 Å resolution and were, until recently, assumed to be formed by the DAD protein. However, when another crystal form of this enzyme was eventually solved at lower resolution, molecular replacement using this new structure as the search model did not give a convincing solution with the original atomic resolution data set. Hence, it was considered that these crystals might have arisen from a protein impurity, although molecular replacement using the structures of common crystallization contaminants as search models again failed. A script to perform molecular replacement using MOLREP in which the first chain of every structure in the PDB was used as a search model was run on a multi-core cluster. This identified a number of prokaryotic phosphate-binding proteins as scoring highly in the MOLREP peak lists. Calculation of an electron-density map at 1.1 Å resolution based on the solution obtained with PDB entry 2q9t allowed most of the amino acids to be identified visually and built into the model. A BLAST search then indicated that the molecule was most probably a phosphate-binding protein from Stenotrophomonas maltophilia (UniProt ID B4SL31; gene ID Smal_2208), and fitting of the corresponding sequence to the atomic resolution map fully corroborated this. Proteins in this family have been linked to the virulence of antibiotic-resistant strains of pathogenic bacteria and with biofilm formation. The structure of the S. maltophilia protein has been refined to an R factor of 10.15% and an Rfree of 12.46% at 1.1 Å resolution. The molecule adopts the type II periplasmic binding protein (PBP) fold with a number of extensively elaborated loop regions. A fully dehydrated phosphate

  6. Detection of pelagic habitat hotspots for skipjack tuna in the Gulf of Bone-Flores Sea, southwestern Coral Triangle tuna, Indonesia.

    Science.gov (United States)

    Zainuddin, Mukti; Farhum, Aisjah; Safruddin, Safruddin; Selamat, Muhammad Banda; Sudirman, Sudirman; Nurdin, Nurjannah; Syamsuddin, Mega; Ridwan, Muhammad; Saitoh, Sei-Ichi

    2017-01-01

    Using remote sensing of sea surface temperature (SST), sea surface height anomaly (SSHA) and chlorophyll-a (Chl-a) together with catch data, we investigated the detection and persistence of important pelagic habitat hotspots for skipjack tuna in the Gulf of Bone-Flores Sea, Indonesia. We analyzed the data for the period between the northwest and southeast monsoon 2007-2011. A pelagic hotspot index was constructed from a model of multi-spectrum satellite-based oceanographic data in relation to skipjack fishing performance. Results showed that skipjack catch per unit efforts (CPUEs) increased significantly in areas of highest pelagic hotspot indices. The distribution and dynamics of habitat hotspots were detected by the synoptic measurements of SST, SSHA and Chl-a ranging from 29.5° to 31.5°C, from 2.5 to 12.5 cm and from 0.15 to 0.35 mg m-3, respectively. Total area of hotspots consistently peaked in May. Validation of skipjack CPUE predicted by our model against observed data from 2012 was highly significant. The key pelagic habitat corresponded with the Chl-a front, which could be related to the areas of relatively high prey abundance (enhanced feeding opportunity) for skipjack. We found that the area and persistence of the potential skipjack habitat hotspots for the 5 years were clearly identified by the 0.2 mg m-3 Chl-a isopleth, suggesting that the Chl-a front provides a key oceanographic indicator for global understanding on skipjack tuna habitat hotspots in the western tropical Pacific Ocean, especially within Coral Triangle tuna.

  7. Testing the Efficacy of Global Biodiversity Hotspots for Insect Conservation: The Case of South African Katydids

    OpenAIRE

    Bazelet, Corinna S.; Thompson, Aileen C.; Naskrecki, Piotr

    2016-01-01

    The use of endemism and vascular plants only for biodiversity hotspot delineation has long been contested. Few studies have focused on the efficacy of global biodiversity hotspots for the conservation of insects, an important, abundant, and often ignored component of biodiversity. We aimed to test five alternative diversity measures for hotspot delineation and examine the efficacy of biodiversity hotspots for conserving a non-typical target organism, South African katydids. Using a 1° fishnet...

  8. Rapid experimental SAD phasing and hot-spot identification with halogenated fragments

    Energy Technology Data Exchange (ETDEWEB)

    Bauman, Joseph D.; Harrison, Jerry Joe E. K.; Arnold, Eddy

    2016-01-01

    Through X-ray crystallographic fragment screening, 4-bromopyrazole was discovered to be a `magic bullet' that is capable of binding at many of the ligand `hot spots' found in HIV-1 reverse transcriptase (RT). The binding locations can be in pockets that are `hidden' in the unliganded crystal form, allowing rapid identification of these sites forin silicoscreening. In addition to hot-spot identification, this ubiquitous yet specific binding provides an avenue for X-ray crystallographic phase determination, which can be a significant bottleneck in the determination of the structures of novel proteins. The anomalous signal from 4-bromopyrazole or 4-iodopyrazole was sufficient to determine the structures of three proteins (HIV-1 RT, influenza A endonuclease and proteinase K) by single-wavelength anomalous dispersion (SAD) from single crystals. Both compounds are inexpensive, readily available, safe and very soluble in DMSO or water, allowing efficient soaking into crystals.

  9. Conservation priorities in a biodiversity hotspot: analysis of narrow endemic plant species in New Caledonia.

    Directory of Open Access Journals (Sweden)

    Adrien S Wulff

    Full Text Available New Caledonia is a global biodiversity hotspot facing extreme environmental degradation. Given the urgent need for conservation prioritisation, we have made a first-pass quantitative assessment of the distribution of Narrow Endemic Species (NES in the flora to identify species and sites that are potentially important for conservation action. We assessed the distributional status of all angiosperm and gymnosperm species using data from taxonomic descriptions and herbarium samples. We characterised species as being NES if they occurred in 3 or fewer locations. In total, 635 of the 2930 assessed species were classed as NES, of which only 150 have been subjected to the IUCN conservation assessment. As the distributional patterns of un-assessed species from one or two locations correspond well with assessed species which have been classified as Critically Endangered or Endangered respectively, we suggest that our distributional data can be used to prioritise species for IUCN assessment. We also used the distributional data to produce a map of "Hotspots of Plant Narrow Endemism" (HPNE. Combined, we used these data to evaluate the coincidence of NES with mining activities (a major source of threat on New Caledonia and also areas of conservation protection. This is to identify species and locations in most urgent need of further conservation assessment and subsequent action. Finally, we grouped the NES based on the environments they occurred in and modelled the habitat distribution of these groups with a Maximum Entropy Species Distribution Model (MaxEnt. The NES were separable into three different groups based primarily on geological differences. The distribution of the habitat types for each group coincide partially with the HPNE described above and also indicates some areas which have high habitat suitability but few recorded NES. Some of these areas may represent under-sampled hotspots of narrow endemism and are priorities for further field work.

  10. European hotspots as evidenced by the Palearctic distribution of songbirds

    NARCIS (Netherlands)

    Sluys, R.; Aliabadian, M.; Roselaar, C.S.; Zachos, F.E.; Habel, J.C.

    2011-01-01

    A database has been created of digitized equal area distribution maps of 2,401 phylogenetic species of songbirds endemic to the Palearctic Region. Geographic distribution of species richness delineated several hotspot regions in the Palearctic, mostly located in mountainous areas. The index of

  11. Generation of mutation hotspots in ageing bacterial colonies

    DEFF Research Database (Denmark)

    Sekowska, Agnieszka; Wendel, Sofie; Christian Fischer, Emil

    2016-01-01

    : most mutations were located in just a few hotspots in the genome, and over time, mutations increasingly were consistent with the involvement of 8-oxo-guanosine, formed exclusively on the transcribed strand. This work provides strong support for retromutagenesis as a general process creating adaptive...

  12. Mortality hotspots: nitrogen cycling in forest soils during vertebrate decomposition

    Science.gov (United States)

    Decomposing plants and animals fundamentally transform their surrounding environments, and serve as a critical source of limiting nutrients for macro- and micro-fauna. Animal mortality hotspots alter soil biogeochemical cycles, and these natural ephemeral nutrient patches are important for maintaini...

  13. Molecular architecture of transcription factor hotspots in early adipogenesis

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Baek, Songjoon; Rabiee, Atefeh

    2014-01-01

    motif on chromatin, and we suggest that this may be a general mechanism for integrating external signals on chromatin. Furthermore, we find evidence of extensive recruitment of transcription factors to hotspots through alternative mechanisms not involving their known motifs and demonstrate...

  14. Atmospheric gravity waves in the Red Sea: a new hotspot

    KAUST Repository

    Magalhaes, J. M.; Araú jo, I. B.; da Silva, J. C. B.; Grimshaw, R. H. J.; Davis, K.; Pineda, J.

    2011-01-01

    The region of the Middle East around the Red Sea (between 32° E and 44° E longitude and 12° N and 28° N latitude) is a currently undocumented hotspot for atmospheric gravity waves (AGWs). Satellite imagery shows evidence that this region is prone

  15. Rainfall-induced landslides in Europe: hotspots and thresholds (Invited)

    Science.gov (United States)

    Cepeda, J.; Jaedicke, C.; Nadim, F.; Kalsnes, B.

    2010-12-01

    This contribution presents preliminary results of the European project SafeLand. SafeLand is a large-scale integrating collaborative research project on landslide risks in Europe, funded by the Seventh Framework Programme for research and technological development (FP7) of the European Commission. SafeLand was launched in May 2009 and will run for three years. The project team, which comprises 27 institutions from 12 European countries, is coordinated by the International Centre for Geohazards (ICG) in Norway. SafeLand aims to develop and implement an integrated and comprehensive approach to help and guide decision-making in connection with mitigation of landslide risks. Quantifying the effects of global change (changes in demography and climate change) on evolution of landslide risk in Europe is one of the main goals of SafeLand. The methodologies are tested in selected hazard and risk "hotspots” in Europe, in turn improving knowledge, methodologies and integration strategies for the management of landslide risk. The present contribution is focused on two components of SafeLand: (1) the identification of landslide hazard and risk hotspots and (2) the estimation and assessment of rainfall thresholds for triggering of landslides. Hotspots of landslide hazard and risk were identified by an objective GIS-based analysis. The results show clearly where landslide pose the largest hazard in Europe and the objective approach allows a ranking of the countries by exposed area and population. In absolute numbers, Italy is the country with the highest amount of area and population exposed. Relative to absolute number of inhabitants and area, small alpine countries such as Lichtenstein and Montenegro score highest where as much as 40% of the population could be exposed. It is obvious that the type and quality of the input data are decisive for the quality of the results. Especially the estimation of extreme precipitation events needs improvement. These preliminary results are

  16. Five-way Smoking Status Classification Using Text Hot-Spot Identification and Error-correcting Output Codes

    OpenAIRE

    Cohen, Aaron M.

    2008-01-01

    We participated in the i2b2 smoking status classification challenge task. The purpose of this task was to evaluate the ability of systems to automatically identify patient smoking status from discharge summaries. Our submission included several techniques that we compared and studied, including hot-spot identification, zero-vector filtering, inverse class frequency weighting, error-correcting output codes, and post-processing rules. We evaluated our approaches using the same methods as the i2...

  17. A hot-spot mutation in CDC42 (p.Tyr64Cys) and novel phenotypes in the third patient with Takenouchi-Kosaki syndrome.

    Science.gov (United States)

    Motokawa, Midori; Watanabe, Satoshi; Nakatomi, Akiko; Kondoh, Tatsuro; Matsumoto, Tadashi; Morifuji, Kanako; Sawada, Hirotake; Nishimura, Toyoki; Nunoi, Hiroyuki; Yoshiura, Koh-Ichiro; Moriuchi, Hiroyuki; Dateki, Sumito

    2018-03-01

    Takenouchi-Kosaki syndrome (TKS) is a congenital malformation syndrome characterized by severe developmental delay, macrothrombocytopenia, camptodactyly, sensorineural hearing loss, and dysmorphic facial features. Recently, a heterozygous de novo mutation (p.Tyr64Cys) in the CDC42 gene, which encodes a key small GTP-binding protein of the Rho-subfamily, was identified in two unrelated patients with TKS. We herein report a third patient with TKS who had the same heterozygous CDC42 mutation. The phenotype of the patient was very similar to those of the two previously reported patients with TKS; however, she also demonstrated novel clinical manifestations, such as congenital hypothyroidism and immunological disturbance. Thus, despite the heterozygous mutation of CDC42 (p.Tyr64Cys) likely being a hot-spot mutation for TKS, its phenotype may be variable. Further studies and the accumulation of patients with CDC42 mutations are needed to clarify the phenotype in patients with TKS and the pathophysiological roles of the CDC42 mutation.

  18. HotSpot Wizard 3.0: web server for automated design of mutations and smart libraries based on sequence input information.

    Science.gov (United States)

    Sumbalova, Lenka; Stourac, Jan; Martinek, Tomas; Bednar, David; Damborsky, Jiri

    2018-05-23

    HotSpot Wizard is a web server used for the automated identification of hotspots in semi-rational protein design to give improved protein stability, catalytic activity, substrate specificity and enantioselectivity. Since there are three orders of magnitude fewer protein structures than sequences in bioinformatic databases, the major limitation to the usability of previous versions was the requirement for the protein structure to be a compulsory input for the calculation. HotSpot Wizard 3.0 now accepts the protein sequence as input data. The protein structure for the query sequence is obtained either from eight repositories of homology models or is modeled using Modeller and I-Tasser. The quality of the models is then evaluated using three quality assessment tools-WHAT_CHECK, PROCHECK and MolProbity. During follow-up analyses, the system automatically warns the users whenever they attempt to redesign poorly predicted parts of their homology models. The second main limitation of HotSpot Wizard's predictions is that it identifies suitable positions for mutagenesis, but does not provide any reliable advice on particular substitutions. A new module for the estimation of thermodynamic stabilities using the Rosetta and FoldX suites has been introduced which prevents destabilizing mutations among pre-selected variants entering experimental testing. HotSpot Wizard is freely available at http://loschmidt.chemi.muni.cz/hotspotwizard.

  19. New geothermal heat flux map of Greenland and the Iceland hotspot track

    Science.gov (United States)

    Martos, Y. M.; Jordan, T. A.; Catalan, M.; Jordan, T. M.; Bamber, J. L.; Vaughan, D. G.

    2017-12-01

    Greenland is the second largest reservoir of water on Earth and about 80% of its surface is covered by ice. It is mainly composed of Archean blocks that collided during the Early Proterozoic. Indirect methods have been used to study its subglacial thermal conditions, geology and lithospheric structure. Numerous regions of basal melting are identified in the central and north Greenland but their relationship with geothermal heat flux is not yet clear. Crustal thickness derived by seismology and gravity data are consistent, showing no significant lateral variations, and providing average values of about 40 and 36 km respectively. Even though Greenland is considered a craton its crust has been affected by the presume passage of the Iceland hotspot since at least 100 Ma. Here we present the newest and highest resolution Curie Depth and geothermal heat flux maps for Greenland as well as their associated uncertainties. For estimating the Curie Depths we applied spectral methods to aeromagnetic data from the World Digital Magnetic Anomaly Map WDMAM2.0. Calculated Curie Depths vary from 25 to 50 km with shallower values located to the east. A thermal model is built based on the 1D heat conduction equation and considering steady state conditions. The thermal parameters are then optimized using local values derived from direct measurements, temperature profiles and more indirect methods such as radar imaging. The heat flux distribution shows higher spatial variability and a very different pattern than previously proposed and with values of 50-80 mW/m2. We identify a NW-SE high heat flux feature crossing Greenland which we correlate with the Iceland hotspot track. Additionally, to evaluate the lithospheric structure we calculate the Bouguer anomaly from GOCO5s satellite free air data and construct several gravity models across the proposed hotspot track. We show that a dense lower crust body in the same location the high heat flux trend is permissible from a gravimetric

  20. Assessment of landscape diversity and determination of landscape hotspots - a case of Slovenia

    Science.gov (United States)

    Perko, Drago; Ciglič, Rok; Hrvatin, Mauro

    2017-04-01

    Areas with high landscape diversity can be regarded as landscape hotspots, and vice versa areas with low landscape diversity can be marked as landscape coldspots. The main purpose of this paper is to use quantitative geoinformatical approach and identify parts of our test area (the country of Slovenia) that can be described as very diverse according to natural landscapes and natural elements. We used different digital raster data of natural elements and landscape classifications and defined landscape diversity and landscape hotspots. We defined diversity for each raster pixel by counting the number of different unique types of landscape elements and types of landscapes in its neighborhood. Namely, the method was used separately to define diversity according to natural elements (types of relief forms, rocks, and vegetation) and diversity according to existing geographical landscape classifications of Slovenia (types of landscapes). In both cases one-tenth of Slovenia's surface with the highest landscape diversity was defined as landscape hotspots. The same applies to the coldspots. Additionally we tested the same method of counting different types of landscapes in certain radius also for the area of Europe in order to find areas that are more diverse at continental level. By doing so we were able to find areas that have similar level of diversity as Slovenia according to different European landscape classifications. Areas with landscape diversity may have an advantage in economic development, especially in tourism. Such areas are also important for biodiversity, habitat, and species diversity. On the other hand, localities where various natural influences mix can also be areas where it is hard to transfer best practices from one place to another because of the varying responses of the landscapes to human intervention. Thus it is important to know where areas with high landscape diversity are.

  1. The epidemiology of road traffic injury hotspots in Kigali, Rwanda from police data

    Directory of Open Access Journals (Sweden)

    Anjni Patel

    2016-08-01

    Full Text Available Abstract Background Road traffic injuries (RTIs are the eighth-leading cause of death worldwide, with low- and middle-income countries sharing a disproportionate number of fatalities. African countries, like Rwanda, carry a higher burden of these fatalities and with increased economic growth, these numbers are expected to rise. We aim to describe the epidemiology of RTIs in Kigali Province, Rwanda and create a hotspot map of crashes from police data. Methods Road traffic crash (RTC report data from January 1, 2013 to December 31, 2013 was collected from Kigali Traffic Police. In addition to analysis of descriptive data, locations of RTCs were mapped and analyzed through exploratory spatial data analysis to determine hotspots. Results A total of 2589 of RTCs were reported with 4689 total victims. The majority of victims were male (94.7 % with an average age of 35.9 years. Cars were the most frequent vehicle involved (43.8 %, followed by motorcycles (14.5 %. Motorcycles had an increased risk of involvement in grievous crashes and pedestrians and cyclists were more likely to have grievous injuries. The hotspots identified were primarily located along the major roads crossing Kigali and the two busiest downtown areas. Conclusions Despite significant headway by the government in RTC prevention, there continue to be high rates of RTIs in Rwanda, specifically with young males and a vulnerable road user population, such as pedestrians and motorcycle users. Improvements in police data and reporting by laypersons could prove valuable for further geographic information system analysis and efforts towards crash prevention and targeting education to motorcycle taxis could help reduce RTIs in a severely affected population.

  2. Recombining without Hotspots: A Comprehensive Evolutionary Portrait of Recombination in Two Closely Related Species of Drosophila

    Science.gov (United States)

    Smukowski Heil, Caiti S.; Ellison, Chris; Dubin, Matthew; Noor, Mohamed A.F.

    2015-01-01

    Meiotic recombination rate varies across the genome within and between individuals, populations, and species in virtually all taxa studied. In almost every species, this variation takes the form of discrete recombination hotspots, determined in some mammals by a protein called PRDM9. Hotspots and their determinants have a profound effect on the genomic landscape, and share certain features that extend across the tree of life. Drosophila, in contrast, are anomalous in their absence of hotspots, PRDM9, and other species-specific differences in the determination of recombination. To better understand the evolution of meiosis and general patterns of recombination across diverse taxa, we present a truly comprehensive portrait of recombination across time, combining recently published cross-based contemporary recombination estimates from each of two sister species with newly obtained linkage-disequilibrium-based historic estimates of recombination from both of these species. Using Drosophila pseudoobscura and Drosophila miranda as a model system, we compare recombination rate between species at multiple scales, and we suggest that Drosophila replicate the pattern seen in human–chimpanzee in which recombination rate is conserved at broad scales. We also find evidence of a species-wide recombination modifier(s), resulting in both a present and historic genome-wide elevation of recombination rates in D. miranda, and identify broad scale effects on recombination from the presence of an inversion. Finally, we reveal an unprecedented view of the distribution of recombination in D. pseudoobscura, illustrating patterns of linked selection and where recombination is taking place. Overall, by combining these estimation approaches, we highlight key similarities and differences in recombination between Drosophila and other organisms. PMID:26430062

  3. The epidemiology of road traffic injury hotspots in Kigali, Rwanda from police data.

    Science.gov (United States)

    Patel, Anjni; Krebs, Elizabeth; Andrade, Luciano; Rulisa, Stephen; Vissoci, João Ricardo N; Staton, Catherine A

    2016-08-02

    Road traffic injuries (RTIs) are the eighth-leading cause of death worldwide, with low- and middle-income countries sharing a disproportionate number of fatalities. African countries, like Rwanda, carry a higher burden of these fatalities and with increased economic growth, these numbers are expected to rise. We aim to describe the epidemiology of RTIs in Kigali Province, Rwanda and create a hotspot map of crashes from police data. Road traffic crash (RTC) report data from January 1, 2013 to December 31, 2013 was collected from Kigali Traffic Police. In addition to analysis of descriptive data, locations of RTCs were mapped and analyzed through exploratory spatial data analysis to determine hotspots. A total of 2589 of RTCs were reported with 4689 total victims. The majority of victims were male (94.7 %) with an average age of 35.9 years. Cars were the most frequent vehicle involved (43.8 %), followed by motorcycles (14.5 %). Motorcycles had an increased risk of involvement in grievous crashes and pedestrians and cyclists were more likely to have grievous injuries. The hotspots identified were primarily located along the major roads crossing Kigali and the two busiest downtown areas. Despite significant headway by the government in RTC prevention, there continue to be high rates of RTIs in Rwanda, specifically with young males and a vulnerable road user population, such as pedestrians and motorcycle users. Improvements in police data and reporting by laypersons could prove valuable for further geographic information system analysis and efforts towards crash prevention and targeting education to motorcycle taxis could help reduce RTIs in a severely affected population.

  4. Recombining without Hotspots: A Comprehensive Evolutionary Portrait of Recombination in Two Closely Related Species of Drosophila.

    Science.gov (United States)

    Smukowski Heil, Caiti S; Ellison, Chris; Dubin, Matthew; Noor, Mohamed A F

    2015-10-01

    Meiotic recombination rate varies across the genome within and between individuals, populations, and species in virtually all taxa studied. In almost every species, this variation takes the form of discrete recombination hotspots, determined in some mammals by a protein called PRDM9. Hotspots and their determinants have a profound effect on the genomic landscape, and share certain features that extend across the tree of life. Drosophila, in contrast, are anomalous in their absence of hotspots, PRDM9, and other species-specific differences in the determination of recombination. To better understand the evolution of meiosis and general patterns of recombination across diverse taxa, we present a truly comprehensive portrait of recombination across time, combining recently published cross-based contemporary recombination estimates from each of two sister species with newly obtained linkage-disequilibrium-based historic estimates of recombination from both of these species. Using Drosophila pseudoobscura and Drosophila miranda as a model system, we compare recombination rate between species at multiple scales, and we suggest that Drosophila replicate the pattern seen in human-chimpanzee in which recombination rate is conserved at broad scales. We also find evidence of a species-wide recombination modifier(s), resulting in both a present and historic genome-wide elevation of recombination rates in D. miranda, and identify broad scale effects on recombination from the presence of an inversion. Finally, we reveal an unprecedented view of the distribution of recombination in D. pseudoobscura, illustrating patterns of linked selection and where recombination is taking place. Overall, by combining these estimation approaches, we highlight key similarities and differences in recombination between Drosophila and other organisms. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  5. Urban emissions hotspots: Quantifying vehicle congestion and air pollution using mobile phone GPS data.

    Science.gov (United States)

    Gately, Conor K; Hutyra, Lucy R; Peterson, Scott; Sue Wing, Ian

    2017-10-01

    On-road emissions vary widely on time scales as short as minutes and length scales as short as tens of meters. Detailed data on emissions at these scales are a prerequisite to accurately quantifying ambient pollution concentrations and identifying hotspots of human exposure within urban areas. We construct a highly resolved inventory of hourly fluxes of CO, NO 2 , NO x , PM 2.5 and CO 2 from road vehicles on 280,000 road segments in eastern Massachusetts for the year 2012. Our inventory integrates a large database of hourly vehicle speeds derived from mobile phone and vehicle GPS data with multiple regional datasets of vehicle flows, fleet characteristics, and local meteorology. We quantify the 'excess' emissions from traffic congestion, finding modest congestion enhancement (3-6%) at regional scales, but hundreds of local hotspots with highly elevated annual emissions (up to 75% for individual roadways in key corridors). Congestion-driven reductions in vehicle fuel economy necessitated 'excess' consumption of 113 million gallons of motor fuel, worth ∼ $415M, but this accounted for only 3.5% of the total fuel consumed in Massachusetts, as over 80% of vehicle travel occurs in uncongested conditions. Across our study domain, emissions are highly spatially concentrated, with 70% of pollution originating from only 10% of the roads. The 2011 EPA National Emissions Inventory (NEI) understates our aggregate emissions of NO x , PM 2.5 , and CO 2 by 46%, 38%, and 18%, respectively. However, CO emissions agree within 5% for the two inventories, suggesting that the large biases in NO x and PM 2.5 emissions arise from differences in estimates of diesel vehicle activity. By providing fine-scale information on local emission hotspots and regional emissions patterns, our inventory framework supports targeted traffic interventions, transparent benchmarking, and improvements in overall urban air quality. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. A recombination hotspot in a schizophrenia-associated region of GABRB2.

    Directory of Open Access Journals (Sweden)

    Siu-Kin Ng

    Full Text Available BACKGROUND: Schizophrenia is a major disorder with complex genetic mechanisms. Earlier, population genetic studies revealed the occurrence of strong positive selection in the GABRB2 gene encoding the beta(2 subunit of GABA(A receptors, within a segment of 3,551 bp harboring twenty-nine single nucleotide polymorphisms (SNPs and containing schizophrenia-associated SNPs and haplotypes. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, the possible occurrence of recombination in this 'S1-S29' segment was assessed. The occurrence of hotspot recombination was indicated by high resolution recombination rate estimation, haplotype diversity, abundance of rare haplotypes, recurrent mutations and torsos in haplotype networks, and experimental haplotyping of somatic and sperm DNA. The sub-segment distribution of relative recombination strength, measured by the ratio of haplotype diversity (H(d over mutation rate (theta, was indicative of a human specific Alu-Yi6 insertion serving as a central recombining sequence facilitating homologous recombination. Local anomalous DNA conformation attributable to the Alu-Yi6 element, as suggested by enhanced DNase I sensitivity and obstruction to DNA sequencing, could be a contributing factor of the increased sequence diversity. Linkage disequilibrium (LD analysis yielded prominent low LD points that supported ongoing recombination. LD contrast revealed significant dissimilarity between control and schizophrenic cohorts. Among the large array of inferred haplotypes, H26 and H73 were identified to be protective, and H19 and H81 risk-conferring, toward the development of schizophrenia. CONCLUSIONS/SIGNIFICANCE: The co-occurrence of hotspot recombination and positive selection in the S1-S29 segment of GABRB2 has provided a plausible contribution to the molecular genetics mechanisms for schizophrenia. The present findings therefore suggest that genome regions characterized by the co-occurrence of positive selection and

  7. Using expert informed GIS to locate important marine social-ecological hotspots.

    Science.gov (United States)

    Mahboubi, Pouyan; Parkes, Margot; Stephen, Craig; Chan, Hing Man

    2015-09-01

    The marine environment provides significant benefits to many local communities. Pressure to develop coastal waterways worldwide creates an urgent need for tools to locate marine spaces that have important social or ecological values, and to quantify their relative importance. The primary objective of this study was to develop, apply and critically assess a tool to identify important social-ecological hotspots in the marine environment. The study was conducted in a typical coastal community in northern British Columbia, Canada. This expert-informed GIS, or xGIS, tool used a survey instrument to draw on the knowledge of local experts from a range of backgrounds with respect to a series of 12 social-ecological value attributes, such as biodiversity, cultural and economic values. We identified approximately 1500 polygons on marine maps and assigned relative values to them using a token distribution exercise. A series of spatial statistical analyses were performed to locate and quantify the relative social-ecological importance of marine spaces and the results were ultimately summarized in a single hotspot map of the entire study area. This study demonstrates the utility of xGIS as a useful tool for stakeholders and environmental managers engaged in the planning and management of marine resources at the local and regional levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Dynamic placement of plasmonic hotspots for super-resolution surface-enhanced Raman scattering.

    Science.gov (United States)

    Ertsgaard, Christopher T; McKoskey, Rachel M; Rich, Isabel S; Lindquist, Nathan C

    2014-10-28

    In this paper, we demonstrate dynamic placement of locally enhanced plasmonic fields using holographic laser illumination of a silver nanohole array. To visualize these focused "hotspots", the silver surface was coated with various biological samples for surface-enhanced Raman spectroscopy (SERS) imaging. Due to the large field enhancements, blinking behavior of the SERS hotspots was observed and processed using a stochastic optical reconstruction microscopy algorithm enabling super-resolution localization of the hotspots to within 10 nm. These hotspots were then shifted across the surface in subwavelength (hotspots. Using this technique, we also show that such subwavelength shifting and localization of plasmonic hotspots has potential for imaging applications. Interestingly, illuminating the surface with randomly shifting SERS hotspots was sufficient to completely fill in a wide field of view for super-resolution chemical imaging.

  9. Hotspots in research on the measurement of medical students' clinical competence from 2012-2016 based on co-word analysis.

    Science.gov (United States)

    Chang, Xing; Zhou, Xin; Luo, Linzhi; Yang, Chengjia; Pan, Hui; Zhang, Shuyang

    2017-09-12

    This study aimed to identify hotspots in research on clinical competence measurements from 2012 to 2016. The authors retrieved literature published between 2012 and 2016 from PubMed using selected medical subject headings (MeSH) terms. They used BibExcel software to generate high-frequency MeSH terms and identified hotspots by co-word analysis and cluster analysis. The authors searched 588 related articles and identified 31 high-frequency MeSH terms. In addition, they obtained 6 groups of high-frequency MeSH terms that reflected the domain hotspots. This study identified 6 hotspots of domain research, including studies on influencing factors and perception evaluation, improving and developing measurement tools, feedback measurement, measurement approaches based on computer simulation, the measurement of specific students in different learning phases, and the measurement of students' communication ability. All of these research topics could provide useful information for educators and researchers to continually conduct in-depth studies.

  10. Urban emissions hotspots: Quantifying vehicle congestion and air pollution using mobile phone GPS data

    International Nuclear Information System (INIS)

    Gately, Conor K.; Hutyra, Lucy R.; Peterson, Scott; Sue Wing, Ian

    2017-01-01

    On-road emissions vary widely on time scales as short as minutes and length scales as short as tens of meters. Detailed data on emissions at these scales are a prerequisite to accurately quantifying ambient pollution concentrations and identifying hotspots of human exposure within urban areas. We construct a highly resolved inventory of hourly fluxes of CO, NO 2 , NO x , PM 2.5 and CO 2 from road vehicles on 280,000 road segments in eastern Massachusetts for the year 2012. Our inventory integrates a large database of hourly vehicle speeds derived from mobile phone and vehicle GPS data with multiple regional datasets of vehicle flows, fleet characteristics, and local meteorology. We quantify the ‘excess’ emissions from traffic congestion, finding modest congestion enhancement (3–6%) at regional scales, but hundreds of local hotspots with highly elevated annual emissions (up to 75% for individual roadways in key corridors). Congestion-driven reductions in vehicle fuel economy necessitated ‘excess’ consumption of 113 million gallons of motor fuel, worth ∼ $415M, but this accounted for only 3.5% of the total fuel consumed in Massachusetts, as over 80% of vehicle travel occurs in uncongested conditions. Across our study domain, emissions are highly spatially concentrated, with 70% of pollution originating from only 10% of the roads. The 2011 EPA National Emissions Inventory (NEI) understates our aggregate emissions of NO x , PM 2.5 , and CO 2 by 46%, 38%, and 18%, respectively. However, CO emissions agree within 5% for the two inventories, suggesting that the large biases in NO x and PM 2.5 emissions arise from differences in estimates of diesel vehicle activity. By providing fine-scale information on local emission hotspots and regional emissions patterns, our inventory framework supports targeted traffic interventions, transparent benchmarking, and improvements in overall urban air quality. - Highlights: • A high resolution, bottom-up inventory of

  11. Scanning For Hotspots In Lamp Filaments

    Science.gov (United States)

    Powers, Charles E.; Van Sant, Tim; Leidecker, Henning

    1993-01-01

    Scanning photometer designed for use in investigation of failures of incandescent lamp filaments. Maps brightness as function of position along each filament to identify bright (hot) spots, occurring at notches and signifying incipient breaks or rewelds. Also used to measure nonuniformity in outputs of such linear devices as light-emitting diodes, and to measure diffraction patterns of lenses.

  12. Hotspot identification of trans-boundary water conflict due to anthropogenic water use and climate change in the future

    Science.gov (United States)

    Ueki, A.; Yoshikawa, S.; Kanae, S.

    2014-12-01

    A significant fraction of world population is projected to experience increased water stress in response to the combined effects of population growth and climate change. Some previous studies have suggested that high water stress had significant causality for civil war, and militarized conflict and trans-boundary water conflict in international river basin. On the other hand, some previous empirical analyses have found that institutionalization (e.g., specific provisions in trans-boundary freshwater treaties) in international river basin was associated with a lower risk of water conflicts during water scarcity. The purpose of this study is to identify these water conflict "hotspots", integrating institutional and governance mechanisms of adaptations to impact of water stress. These adaptations is classified to 4 abilities and skills and then used to calculate the adaptive capacity. The adaptive capacity includes the way to manage water conflict effectively, plan to deal with uncertainty in the future, alter current situation and create institutionalization with common perspective throughout the whole activities. This study identifies water conflict "hotspots" by combining high water stress areas projected by a global water resource model and a lower degree of the adaptive capacity. This study finds that 9 water conflict "hotspots" in Africa, Asia and South America.

  13. Hot-spot analysis to dissect the functional protein-protein interface of a tRNA-modifying enzyme.

    Science.gov (United States)

    Jakobi, Stephan; Nguyen, Tran Xuan Phong; Debaene, François; Metz, Alexander; Sanglier-Cianférani, Sarah; Reuter, Klaus; Klebe, Gerhard

    2014-10-01

    Interference with protein-protein interactions of interfaces larger than 1500 Ų by small drug-like molecules is notoriously difficult, particularly if targeting homodimers. The tRNA modifying enzyme Tgt is only functionally active as a homodimer. Thus, blocking Tgt dimerization is a promising strategy for drug therapy as this protein is key to the development of Shigellosis. Our goal was to identify hot-spot residues which, upon mutation, result in a predominantly monomeric state of Tgt. The detailed understanding of the spatial location and stability contribution of the individual interaction hot-spot residues and the plasticity of motifs involved in the interface formation is a crucial prerequisite for the rational identification of drug-like inhibitors addressing the respective dimerization interface. Using computational analyses, we identified hot-spot residues that contribute particularly to dimer stability: a cluster of hydrophobic and aromatic residues as well as several salt bridges. This in silico prediction led to the identification of a promising double mutant, which was validated experimentally. Native nano-ESI mass spectrometry showed that the dimerization of the suggested mutant is largely prevented resulting in a predominantly monomeric state. Crystal structure analysis and enzyme kinetics of the mutant variant further support the evidence for enhanced monomerization and provide first insights into the structural consequences of the dimer destabilization. © 2014 Wiley Periodicals, Inc.

  14. Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease*

    Science.gov (United States)

    Dewhurst, Henry; Sundararaman, Niveda

    2016-01-01

    Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable

  15. Proteome-wide Structural Analysis of PTM Hotspots Reveals Regulatory Elements Predicted to Impact Biological Function and Disease.

    Science.gov (United States)

    Torres, Matthew P; Dewhurst, Henry; Sundararaman, Niveda

    2016-11-01

    Post-translational modifications (PTMs) regulate protein behavior through modulation of protein-protein interactions, enzymatic activity, and protein stability essential in the translation of genotype to phenotype in eukaryotes. Currently, less than 4% of all eukaryotic PTMs are reported to have biological function - a statistic that continues to decrease with an increasing rate of PTM detection. Previously, we developed SAPH-ire (Structural Analysis of PTM Hotspots) - a method for the prioritization of PTM function potential that has been used effectively to reveal novel PTM regulatory elements in discrete protein families (Dewhurst et al., 2015). Here, we apply SAPH-ire to the set of eukaryotic protein families containing experimental PTM and 3D structure data - capturing 1,325 protein families with 50,839 unique PTM sites organized into 31,747 modified alignment positions (MAPs), of which 2010 (∼6%) possess known biological function. Here, we show that using an artificial neural network model (SAPH-ire NN) trained to identify MAP hotspots with biological function results in prediction outcomes that far surpass the use of single hotspot features, including nearest neighbor PTM clustering methods. We find the greatest enhancement in prediction for positions with PTM counts of five or less, which represent 98% of all MAPs in the eukaryotic proteome and 90% of all MAPs found to have biological function. Analysis of the top 1092 MAP hotspots revealed 267 of truly unknown function (containing 5443 distinct PTMs). Of these, 165 hotspots could be mapped to human KEGG pathways for normal and/or disease physiology. Many high-ranking hotspots were also found to be disease-associated pathogenic sites of amino acid substitution despite the lack of observable PTM in the human protein family member. Taken together, these experiments demonstrate that the functional relevance of a PTM can be predicted very effectively by neural network models, revealing a large but testable

  16. Seismic Evidence for Lower Mantle Plume Under the Yellowstone Hotspot

    Science.gov (United States)

    Nelson, P.; Grand, S.

    2017-12-01

    The mantle plume hypothesis for the origin of intraplate volcanism has been controversial since its inception in the 1970s. The hypothesis proposes hot narrow upwelling of rock rooted at the core mantle boundary (CMB) rise through the mantle and interact with the base of the lithosphere forming linear volcanic systems such as Hawaii and Yellowstone. Recently, broad lower mantle (>500 km in diameter) slow velocity conduits, most likely thermochemical in origin, have been associated with some intraplate volcanic provinces (French and Romanowicz, 2015). However, the direct detection of a classical thin thermal plume in the lower mantle using travel time tomography has remained elusive (Anderson and Natland, 2014). Here we present a new shear wave tomography model for the mantle beneath the western United States that is optimized to find short wavelength, sub-vertical structures in the lower mantle. Our approach uses carefully measured SKS and SKKS travel times recorded by dense North American seismic networks in conjunction with finite frequency kernels to build on existing tomography models. We find the presence of a narrow ( 300 km diameter) well isolated cylindrically shaped slow anomaly in the lower most mantle which we associate with the Yellowstone Hotspot. The conduit has a 2% reduction in shear velocity and is rooted at the CMB near the California/Arizona/Nevada border. A cross sectional view through the anomaly shows that it is slightly tilted toward the north until about 1300 km depth where it appears to weaken and deflect toward the surficial positon of the hotspot. Given the anomaly's strength, proximity to the Yellowstone Hotspot, and morphology we argue that a thermal plume interpretation is the most reasonable. Our results provide strong support for a lower mantle plume origin of the Yellowstone hotspot and more importantly the existence of deep thermal plumes.

  17. Biogeographic distribution patterns and their correlates in the diverse frog fauna of the Atlantic Forest hotspot.

    Science.gov (United States)

    Vasconcelos, Tiago S; Prado, Vitor H M; da Silva, Fernando R; Haddad, Célio F B

    2014-01-01

    Anurans are a highly diverse group in the Atlantic Forest hotspot (AF), yet distribution patterns and species richness gradients are not randomly distributed throughout the biome. Thus, we explore how anuran species are distributed in this complex and biodiverse hotspot, and hypothesize that this group can be distinguished by different cohesive regions. We used range maps of 497 species to obtain a presence/absence data grid, resolved to 50×50 km grain size, which was submitted to k-means clustering with v-fold cross-validation to determine the biogeographic regions. We also explored the extent to which current environmental variables, topography, and floristic structure of the AF are expected to identify the cluster patterns recognized by the k-means clustering. The biogeographic patterns found for amphibians are broadly congruent with ecoregions identified in the AF, but their edges, and sometimes the whole extent of some clusters, present much less resolved pattern compared to previous classification. We also identified that climate, topography, and vegetation structure of the AF explained a high percentage of variance of the cluster patterns identified, but the magnitude of the regression coefficients shifted regarding their importance in explaining the variance for each cluster. Specifically, we propose that the anuran fauna of the AF can be split into four biogeographic regions: a) less diverse and widely-ranged species that predominantly occur in the inland semideciduous forests; b) northern small-ranged species that presumably evolved within the Pleistocene forest refugia; c) highly diverse and small-ranged species from the southeastern Brazilian mountain chain and its adjacent semideciduous forest; and d) southern species from the Araucaria forest. Finally, the high congruence among the cluster patterns and previous eco-regions identified for the AF suggests that preserving the underlying habitat structure helps to preserve the historical and ecological

  18. Borneo and Indochina are major evolutionary hotspots for Southeast Asian biodiversity.

    Science.gov (United States)

    de Bruyn, Mark; Stelbrink, Björn; Morley, Robert J; Hall, Robert; Carvalho, Gary R; Cannon, Charles H; van den Bergh, Gerrit; Meijaard, Erik; Metcalfe, Ian; Boitani, Luigi; Maiorano, Luigi; Shoup, Robert; von Rintelen, Thomas

    2014-11-01

    Tropical Southeast (SE) Asia harbors extraordinary species richness and in its entirety comprises four of the Earth's 34 biodiversity hotspots. Here, we examine the assembly of the SE Asian biota through time and space. We conduct meta-analyses of geological, climatic, and biological (including 61 phylogenetic) data sets to test which areas have been the sources of long-term biological diversity in SE Asia, particularly in the pre-Miocene, Miocene, and Plio-Pleistocene, and whether the respective biota have been dominated by in situ diversification, immigration and/or emigration, or equilibrium dynamics. We identify Borneo and Indochina, in particular, as major "evolutionary hotspots" for a diverse range of fauna and flora. Although most of the region's biodiversity is a result of both the accumulation of immigrants and in situ diversification, within-area diversification and subsequent emigration have been the predominant signals characterizing Indochina and Borneo's biota since at least the early Miocene. In contrast, colonization events are comparatively rare from younger volcanically active emergent islands such as Java, which show increased levels of immigration events. Few dispersal events were observed across the major biogeographic barrier of Wallace's Line. Accelerated efforts to conserve Borneo's flora and fauna in particular, currently housing the highest levels of SE Asian plant and mammal species richness, are critically required. © The Author(s) 2014. Published by Oxford University Press, on behalf of the Society of Systematic Biologists. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Developing Socio-Techno-Economic-Political (STEP Solutions for Addressing Resource Nexus Hotspots

    Directory of Open Access Journals (Sweden)

    Bassel Daher

    2018-02-01

    Full Text Available The challenge of meeting increasing water, energy, and food needs is linked not only to growing demands globally, but also to the growing interdependency between these interconnected resource systems. Pressures on these systems will emerge to become hotspots with different characteristics, and will require a fresh look at the challenges existing both within each of the resource systems and at their respective interfaces. Proposing solutions to address different resource hotspots must be multi-faceted and need to acknowledge the multiple dimensions of the biophysical water, energy, and food systems, and the players connected with them. This commentary first explores the multiple dimensions of water, energy, and food systems as these relate to government, business, and society. It then identifies contemporary critical questions at the interface of these stressed resource systems. A 3-Filter framework is then introduced for vetting the feasibility of proposed resource allocation scenarios and to account for the bio-physical resource interactions and trade-offs, the stakeholder interactions and trade-offs, and to address governance and financing schemes for carrying forward the implementation of those scenarios.

  20. Roadkill hotspots in a protected area of Cerrado in Brazil: planning actions to conservation

    Directory of Open Access Journals (Sweden)

    Bruno H Saranholi

    2016-05-01

    Full Text Available Objective. Here we aimed to identify the main points of animal death by roadkill in the view of helping mitigation plans and reducing the impact over the local fauna of a protected area. Materials and methods. We surveyed the roads around a protected area of Cerrado (São Paulo, Brazil from May 2012 to August 2013. We recorded the local of roadkills, biometric and morphologic data of the animals, and collected samples of tissue for molecular species confirmation. Results. Thirty-one roadkilled animals were registered, including threatened species: Leopardus pardalis; Cuniculus paca and Chrysocyon brachyurus. Most roadkills were represented by mammals (54.8% and reptiles (38.7%, and the mortality rate was 1.46 animals/km/year. Three roadkill hotspots were detected, suggesting that they were important points of animal crossing, probably because of the existence of natural remnant vegetation and intersection of roads by riparian vegetation. Conclusions. This work provided strong evidence of the most critical points where mitigation strategies should be immediately implemented and highlighted the importance of detecting roadkill hotspots and the species or taxonomic groups more affected, helping to elaborate effective actions that can improve fauna conservation.

  1. Biocomplexity and conservation of biodiversity hotspots: three case studies from the Americas.

    Science.gov (United States)

    Callicott, J Baird; Rozzi, Ricardo; Delgado, Luz; Monticino, Michael; Acevedo, Miguel; Harcombe, Paul

    2007-02-28

    The perspective of 'biocomplexity' in the form of 'coupled natural and human systems' represents a resource for the future conservation of biodiversity hotspots in three direct ways: (i) modelling the impact on biodiversity of private land-use decisions and public land-use policies, (ii) indicating how the biocultural history of a biodiversity hotspot may be a resource for its future conservation, and (iii) identifying and deploying the nodes of both the material and psycho-spiritual connectivity between human and natural systems in service to conservation goals. Three biocomplexity case studies of areas notable for their biodiversity, selected for their variability along a latitudinal climate gradient and a human-impact gradient, are developed: the Big Thicket in southeast Texas, the Upper Botanamo River Basin in eastern Venezuela, and the Cape Horn Archipelago at the austral tip of Chile. More deeply, the biocomplexity perspective reveals alternative ways of understanding biodiversity itself, because it directs attention to the human concepts through which biodiversity is perceived and understood. The very meaning of biodiversity is contestable and varies according to the cognitive lenses through which it is perceived.

  2. Drastic underestimation of amphipod biodiversity in the endangered Irano-Anatolian and Caucasus biodiversity hotspots.

    Science.gov (United States)

    Katouzian, Ahmad-Reza; Sari, Alireza; Macher, Jan N; Weiss, Martina; Saboori, Alireza; Leese, Florian; Weigand, Alexander M

    2016-03-01

    Biodiversity hotspots are centers of biological diversity and particularly threatened by anthropogenic activities. Their true magnitude of species diversity and endemism, however, is still largely unknown as species diversity is traditionally assessed using morphological descriptions only, thereby ignoring cryptic species. This directly limits evidence-based monitoring and management strategies. Here we used molecular species delimitation methods to quantify cryptic diversity of the montane amphipods in the Irano-Anatolian and Caucasus biodiversity hotspots. Amphipods are ecosystem engineers in rivers and lakes. Species diversity was assessed by analysing two genetic markers (mitochondrial COI and nuclear 28S rDNA), compared with morphological assignments. Our results unambiguously demonstrate that species diversity and endemism is dramatically underestimated, with 42 genetically identified freshwater species in only five reported morphospecies. Over 90% of the newly recovered species cluster inside Gammarus komareki and G. lacustris; 69% of the recovered species comprise narrow range endemics. Amphipod biodiversity is drastically underestimated for the studied regions. Thus, the risk of biodiversity loss is significantly greater than currently inferred as most endangered species remain unrecognized and/or are only found locally. Integrative application of genetic assessments in monitoring programs will help to understand the true magnitude of biodiversity and accurately evaluate its threat status.

  3. Biodiversity conservation in Costa Rica: a correspondence analysis between identified biodiversity hotspots (Araceae, Arecaceae, Bromeliaceae, and Scarabaeinae and conservation priority life zones Conservación de la biodiversidad en Costa Rica: análisis de la correspondencia entre áreas identificadas clave por su biodiversidad (Araceae, Arecaceae, Bromeliaceae y Scarabaeinae y zonas de vida prioritarias para la conservación

    Directory of Open Access Journals (Sweden)

    Bert Kohlmann

    2010-08-01

    Full Text Available This paper undertook an analysis of the distribution of high species richness and areas of endemism based on plants (Araceae, Arecaceae, and Bromeliaceae and dung beetles (Scarabaeinae inhabiting the different Holdridge Life Zones of Costa Rica. Using a geographic information system (GIS we analyzed biogeographic provinces, in terms of their representativity in sampling areas, life zones, and protected areas. Species richness and endemism maps served as a base for conducting a gap analysis and defining 6 different levels of high priority conservation areas. What percentages of these priority areas are under some type of protection or conservation scheme and which of these areas should be enlarged were also investigated. The degree of feasibility that these areas under protection have for enlargement is indicated. A list is included of all the aforementioned registered species for Costa Rica, as well as their presence in the different Holdridge Life Zones and their endemism status. Four areas with the highest species richness were identified, and 3 new areas of endemism are proposed. The most important conservation priority areas are the tropical wet forests on the northeastern lowlands, the Osa Peninsula region, and the premontane wet forest along the Guanacaste, Tilarán and Central mountain ranges. This study clearly demonstrates the need to include and compare different groups of organisms in biodiversity-endemism studies, in order to obtain more robust and finer-grained studies.El presente estudio analiza la distribución de áreas de alta riqueza específica y endemismos basado en plantas (Araceae, Arecaceae, y Bromeliaceae y escarabajos del estiércol (Scarabaeinae, que habitan las diferentes Zonas de Vida de Holdridge en Costa Rica. Mediante el uso de un sistema de información geográfica (SIG analizamos provincias biogeográficas, en relación a la representatividad de las áreas de muestreo, las zonas de vida y las áreas protegidas

  4. European Atlantic: the hottest oil spill hotspot worldwide

    Science.gov (United States)

    Vieites, David R.; Nieto-Román, Sandra; Palanca, Antonio; Ferrer, Xavier; Vences, Miguel

    2004-11-01

    Oil spills caused by maritime transport of petroleum products are still an important source of ocean pollution, especially in main production areas and along major transport routes. We here provide a historical and geographic analysis of the major oil spills (>700 t) since 1960. Spills were recorded from several key marine ecosystems and marine biodiversity hotspots. The past four decades have been characterized by an overall decrease in the number of accidents and tonnes of oil spilled in the sea, but this trend was less distinct in the European Atlantic area. Recent black tides from the Erika and Prestige vessels provided new evidence for the high risk of accidents with serious ecological impact in this area, which according to our analysis is historically the most important oil spill hotspot worldwide. The English Channel and waters around Galicia in Spain were the areas with most accidents. Maritime transport in European Atlantic waters has been predicted to continue increasing. Together with our own results this suggests that, in addition to measures for increased traffic safety, deployment of emergency capacities in the spill hotspot areas may be crucial for a sustainable conservation of sea resources and ecosystems.

  5. Hotspot temperature calculation and quench analysis on ITER busbar

    International Nuclear Information System (INIS)

    Rong, J.; Huang, X.Y.; Song, Y.T.; Wu, S.T.

    2014-01-01

    Highlights: • The hotspot temperature is calculated in the case of different extra copper in this paper. • The MQE (minimum quench energy) is carried out as the external heating to trigger a quench in busbar. • The temperature changes after quench is analyzed by Gandalf code in the case of different extra copper and no helium. • The normal length is carried out in the case of different extra copper by Gandalf code. - Abstract: This paper describes the analysis of ITER feeder busbar, the hotspot temperature of busbar is calculated by classical method in the case of 0%, 50%, 75% and 100% extra copper (copper strands). The quench behavior of busbar is simulated by 1-D Gandalf code, and the MQE (minimum quench energy) is estimated in classical method as initial external heat in Gandalf input file. The temperature and the normal length of conductor are analyzed in the case of 0%, 50% and 100% extra copper and no helium. By hotspot temperature, conductor temperature and normal length are contrasted in different extra copper cases, it is shown that the extra copper play an important role in quench protecting

  6. Dynamics of Reactive Microbial Hotspots in Concentration Gradient.

    Science.gov (United States)

    Hubert, A.; Farasin, J.; Tabuteau, H.; Dufresne, A.; Meheust, Y.; Le Borgne, T.

    2017-12-01

    In subsurface environments, bacteria play a major role in controlling the kinetics of a broad range of biogeochemical reactions. In such environments, nutrients fluxes and solute concentrations needed for bacteria metabolism may be highly variable in space and intermittent in time. This can lead to the formation of reactive hotspots where and when conditions are favorable to particular microorganisms, hence inducing biogeochemical reaction kinetics that differ significantly from those measured in homogeneous model environments. To investigate the impact of chemical gradients on the spatial structure and temporal dynamics of subsurface microorganism populations, we develop microfluidic cells allowing for a precise control of flow and chemical gradient conditions, as well as quantitative monitoring of the bacteria's spatial distribution and biofilm development. Using the non-motile Escherichia coli JW1908-1 strain and Gallionella capsiferriformans ES-2 as model organisms, we investigate the behavior and development of bacteria over a range of single and double concentration gradients in the concentrations of nutrients, electron donors and electron acceptors. We measure bacterial activity and population growth locally in precisely known hydrodynamic and chemical environments. This approach allows time-resolved monitoring of the location and intensity of reactive hotspots in micromodels as a function of the flow and chemical gradient conditions. We compare reactive microbial hotspot dynamics in our micromodels to classic growth laws and well-known growth parameters for the laboratory model bacteria Escherichia coli.We also discuss consequences for the formation and temporal dynamics of biofilms in the subsurface.

  7. Towards biodiversity hotspots effective for conserving mammals with small geographic ranges

    Science.gov (United States)

    Carrara, Rodolfo; San Blas, Germán; Agrain, Federico; Roig-Juñent, Sergio

    2017-01-01

    The main goal of using global biodiversity hotspots for conservation purposes is to protect taxa with small geographic ranges because these are highly vulnerable to extinction. However, the extent to what different hotspots types are effective for meeting this goal remains controversial because hotspots have been previously defined as either the richest or most threatened and richest sites in terms of total, endemic or threatened species. In this regard, the use of species richness to set conservation priorities is widely discussed because strategies focused on this diversity measure tend to miss many of the taxa with small geographic ranges. Here we use data on global terrestrial mammal distributions to show that, hotspots of total species, endemism and threat defined in terms of species richness are effective in including 27%, 29% and 11% respectively, of the taxa with small geographic ranges. Whilst, the same hotspot types defined in terms of a simple diversity index, which is a function of species richness and range-size rarity, include 68%, 44% and 90% respectively, of these taxa. In addition, we demonstrate that index hotspot types are highly efficient because they conserve 79% of mammal species (21% more species than richness hotspot types), with 59% of species shared by three hotspot types (31% more than richness hotspot types). These results suggest that selection of different diversity measures to define hotspots may strongly affect the achievement of conservation goals.

  8. What makes labour and birth traumatic? A survey of intrapartum 'hotspots'.

    Science.gov (United States)

    Harris, Rachel; Ayers, Susan

    2012-01-01

    Evidence suggests between 1% and 6% of women develop post-traumatic stress disorder (PTSD) after childbirth. 'Hotspots' are moments of extreme distress during traumatising events that are implicated in symptoms of PTSD. This cross-sectional internet survey of hotspots examined (1) the content of intrapartum hotspots and (2) whether particular events, cognitions or emotions during hotspots are related to PTSD. Women (N = 675) who experienced a difficult or traumatic birth completed a questionnaire composed of a validated measure of PTSD, questions concerning the existence of hotspots, and a newly developed measure of emotions and cognitions during hotspots. The majority of women (67.4%) reported at least one hotspot during birth and 52.9% had re-experiencing symptoms of these hotspots. Women were more likely to have PTSD if hotspots involved fear and lack of control (odds ratio (OR) 1.30, 95% CI 1.17-1.43) or intrapartum dissociation (OR 1.12, 95% CI 1.05-1.19). Risk of PTSD was higher if hotspots concerned interpersonal difficulties (OR 4.34, 95% CI 2.15-8.77) or obstetric complications (OR 3.35, 95% CI 1.64-6.87) compared to complications with the baby.

  9. Forest and Land Fire Prevention Through the Hotspot Movement Pattern Approach

    Science.gov (United States)

    Turmudi, T.; Kardono, P.; Hartanto, P.; Ardhitasari, Y.

    2018-02-01

    Indonesia has experienced a great forest fire disaster in 2015. The losses incurred were enormous. But actually the incidence of forest and land fires occurs almost every year. Various efforts were made to cope with the fire disaster. The appearance of a hotspot becomes an early indication of the fire incident both location and time. By studying the location and time of the hotspot's appearance indicates that the hotspot has certain movement patterns from year to year. This study aims to show the pattern of movement of hotspots from year to year that can be used for the prevention of forest and land fires. The method used is time series analysis of land cover and hotspot distribution. The data used were land cover data from 2005 to 2016, hotspot data from 2005 to 2016. The location of this study is the territory of Meranti Kepulauan District. The results show that the highest hotspot is 425 hotspots occurs in the shrubs and bushes. From year to year, the pattern of hotspot movement occurs in the shrubs and bushes cover. The hotspot pattern follows the direction of unused land for cultivation and is dominated by shrubs. From these results, we need to pay more attentiont for the land with the cover of shrubs adjacent to the cultivated land.

  10. Predicting Hotspots for Influenza Virus Reassortment

    Science.gov (United States)

    Gilbert, Marius; Martin, Vincent; Cappelle, Julien; Hosseini, Parviez; Njabo, Kevin Y.; Abdel Aziz, Soad; Xiao, Xiangming; Daszak, Peter; Smith, Thomas B.

    2013-01-01

    The 1957 and 1968 influenza pandemics, each of which killed ≈1 million persons, arose through reassortment events. Influenza virus in humans and domestic animals could reassort and cause another pandemic. To identify geographic areas where agricultural production systems are conducive to reassortment, we fitted multivariate regression models to surveillance data on influenza A virus subtype H5N1 among poultry in China and Egypt and subtype H3N2 among humans. We then applied the models across Asia and Egypt to predict where subtype H3N2 from humans and subtype H5N1 from birds overlap; this overlap serves as a proxy for co-infection and in vivo reassortment. For Asia, we refined the prioritization by identifying areas that also have high swine density. Potential geographic foci of reassortment include the northern plains of India, coastal and central provinces of China, the western Korean Peninsula and southwestern Japan in Asia, and the Nile Delta in Egypt. PMID:23628436

  11. Multiwavelength study of Cygnus A. V. The hotspots in the lobe

    Science.gov (United States)

    Pyrzas, S.; Steenbrugge, K. C.; Blundell, K. M.

    2015-02-01

    Context. The jets in Faranoff-Riley type II AGN are supposed come to an abrupt halt in hotspots on opposite sides of the nucleus. Quite commonly, two hotspots are observed in each lobe. The origin of the second hotspot is currently poorly understood. Aims: Our aims are to determine the origin of the secondary hotspot in the western lobe of Cygnus A from high resolution multifrequency radio images; to determine the minimum Lorentz factor of the electrons in the hotspots, often referred to as the low-energy turnover; and to study the magnetic field configuration of the hotspots. Methods: We used 151 MHz Merlin and 327 MHz, 1.4, 5, 8, 15, and 43 GHz VLA images to determine the centroid of the peak luminosity, the spectral shape, and polarization fraction of both hotspots in the western lobe of Cygnus A. Results: We find a spatial shift in peak luminosity between the lower and higher frequency images for both hotspots. We determine the minimum Lorentz factor of the electrons to be ~1000, and show that most of the emission from the primary hotspot is linearly polarized. The minimum energy magnetic field strength is found to range between ~0.14 and ~0.5 mG in both the primary and secondary hotspots. Conclusions: From the low polarization and the determined outflow velocity, we conclude that the secondary hotspot is no longer a strong shock, and is an expanding, and hence a fading hotspot. This hotspot has an age that is of the same order of magnitude as the jet precession period.

  12. Key Biodiversity Areas in the Indo-Burma Hotspot: Process, Progress and Future Directions

    Directory of Open Access Journals (Sweden)

    A.W. Tordoff

    2012-08-01

    Full Text Available Key Biodiversity Areas (KBAs provide geographic targets for the expansion of protected area coverage, and identify sites for urgent conservation action. Identification of KBAs in the Indo-Burma Hotspot was undertaken during 2003, for a region of analysis comprising Cambodia, Lao PDR, Myanmar (Burma, Thailand and Vietnam, plus parts of southern China. The starting point was information on 282 Important Bird Areas identified by BirdLife International and collaborators. These data were then overlaid with point locality data on globally threatened mammals, reptiles, amphibians, freshwater fish and plants, with additional KBAs identified as required. Through this process, a total of 438 KBAs were identified, covering 258,085km2 or 11.5 percent of the region of analysis. Only 58 percent of the KBAs are wholly or partly included within protected areas, suggesting that there may be a need for further expansion of protected area networks, particularly in Myanmar and Vietnam. The criteria for KBA identification are triggered by 812 species, of which 23 are believed only to occur at a single KBA globally. The KBAs have proven to be a useful conservation priority setting tool in Indo-Burma, helping to guide investments by various donors and application of environmental safeguard policies by international financial institutions. There are fewer examples of KBAs being used to guide expansion of protected area systems in Indo-Burma. In large part, this is because the period of rapid expansion of protected areas in most hotspot countries predated the KBA identification process, and political support for further significant expansion is currently limited.

  13. Five-way smoking status classification using text hot-spot identification and error-correcting output codes.

    Science.gov (United States)

    Cohen, Aaron M

    2008-01-01

    We participated in the i2b2 smoking status classification challenge task. The purpose of this task was to evaluate the ability of systems to automatically identify patient smoking status from discharge summaries. Our submission included several techniques that we compared and studied, including hot-spot identification, zero-vector filtering, inverse class frequency weighting, error-correcting output codes, and post-processing rules. We evaluated our approaches using the same methods as the i2b2 task organizers, using micro- and macro-averaged F1 as the primary performance metric. Our best performing system achieved a micro-F1 of 0.9000 on the test collection, equivalent to the best performing system submitted to the i2b2 challenge. Hot-spot identification, zero-vector filtering, classifier weighting, and error correcting output coding contributed additively to increased performance, with hot-spot identification having by far the largest positive effect. High performance on automatic identification of patient smoking status from discharge summaries is achievable with the efficient and straightforward machine learning techniques studied here.

  14. Mapping soil erosion hotspots and assessing the potential impacts of land management practices in the highlands of Ethiopia

    Science.gov (United States)

    Tamene, Lulseged; Adimassu, Zenebe; Ellison, James; Yaekob, Tesfaye; Woldearegay, Kifle; Mekonnen, Kindu; Thorne, Peter; Le, Quang Bao

    2017-09-01

    An enormous effort is underway in Ethiopia to address soil erosion and restore overall land productivity. Modelling and participatory approaches can be used to delineate erosion hotspots, plan site- and context-specific interventions and assess their impacts. In this study, we employed a modelling interface developed based on the Revised Universal Soil Loss Equation adjusted by the sediment delivery ratio to map the spatial distribution of net soil loss and identify priority areas of intervention. Using the modelling interface, we also simulated the potential impacts of different soil and water conservation measures in reducing net soil loss. Model predictions showed that net soil loss in the study area ranges between 0.4 and 88 t ha- 1 yr- 1 with an average of 12 t ha- 1 yr- 1. The dominant soil erosion hotspots were associated with steep slopes, gullies, communal grazing and cultivated areas. The average soil loss observed in this study is higher than the tolerable soil loss rate estimated for the highland of Ethiopia. The scenario analysis results showed that targeting hotspot areas where soil loss exceeds 10 t ha- 1 yr- 1 could reduce net soil loss to the tolerable limit (interventions. Future work should include cost-benefit and tradeoff analyses of the various management options for achieving a given level of erosion reduction.

  15. The evolution of publication hotspots in the field of telemedicine from 1962 to 2015 and differences among six countries.

    Science.gov (United States)

    Wang, Yanjun; Zhao, Ye; Zheng, Jianzhong; Zhang, Ailian; Dong, Haiyuan

    2018-04-01

    Introduction Telemedicine has been implemented in many countries and has captured the attention of many researchers. Herein, we aim to quantify publication hotspots in the field of telemedicine, analyse their evolution, compare them in different countries, and provide visual representations. Methods We used software tools to process PubMed entries for a 54-year period and identified publication hotspots using keyword frequency analysis. We employed a keyword co-occurrence analysis, principal component analysis, multidimensional scaling analysis, and network visualization technology. Results The number of Medical Subject Heading (MeSH) terms increased with time. The most common subcategories of telemedicine between 1962 and 2015 were Remote Consultation, Teleradiology, and Telepathology. The most popular information communication technologies in telemedicine publications were related to the Internet and cell phones. The topics of Patient Satisfaction, Treatment Outcomes, and Home Care Services associated with telemedicine were highlighted after the 1990s. Use frequency of the terms Cell Phones and Self-Care increased drastically in the past six years, and the publication focus in six countries that had the highest output was different. Knowledge network maps and perceptual maps show the relationship between high-frequency MeSH terms. Discussion The telemedicine field has experienced significant growth and expansion in knowledge and innovation in the last 54 years. Publication hotspots for telemedicine lean towards clinical treatment, home care services, and personal care, and countries emphasize publishing in areas related to their national characteristics. This study quantitatively discusses publication hotspots, provides an objective and systematic understanding of this field, and suggests directions for future telemedicine research.

  16. Spatial Distribution of Volcanic Hotspots and Paterae on Io: Implications for Tidal Heating Models and Magmatic Pathways

    Science.gov (United States)

    Hamilton, C. W.; Beggan, C. D.; Lopes, R.; Williams, D. A.; Radenbaugh, J.

    2011-01-01

    Io, the innermost of Jupiter's Galilean satellites, is the most volcanically active body in the Solar. System. Io's global mean heat flow is approximately 2 W/square m, which is approximately 20 times larger than on Earth. High surface temperatures concentrate within "hotspots" and, to date, 172 Ionian hotspots have been identified by spacecraft and Earth-based telescopes. The Laplace resonance between Io, Europa, and Ganymede maintains these satellites in noncircular orbits and causes displacement of their tidal bulges as the overhead position of Jupiter changes for each moon. Gravitational interactions between Jupiter and Io dominate the orbital evolution of the Laplacian system and generate enormous heat within to as tidal energy is dissipated. If this energy were transferred out of Io at the same rate as it is generated, then the associated surface heat flux would be 2.24 +/- 0.45 W/square m. This estimate is in good agreement with observed global heat flow, but to better constrain tidal dissipation mechanisms and infer how thermal energy is transferred to Io's surface, it is critical to closely examine the spatial distribution of volcanic features. End-member tidal dissipation models either consider that heating occurs completely in the mantle, or completely in the asthenosphere. Mixed models typically favor one-third mantle and two-thirds asthenosphere heating. Recent models also consider the effects of mantle-asthenosphere boundary permeability and asthenospheric instabilities. Deep-mantle heating models predict maximum surface heat flux near the poles, whereas asthenosphere heating models predict maxima near the equator-particularly in the Sub-Jovian and Anti-Jovian hemispheres, with smaller maxima occurring at orbit tangent longitudes. Previous studies have examined the global distribution of Ionian hotspots and patera (i.e., irregular or complex craters with scalloped edges that are generally interpreted to be volcanic calderas), but in this study, we

  17. Analysis of Traffic Crashes Involving Pedestrians Using Big Data: Investigation of Contributing Factors and Identification of Hotspots.

    Science.gov (United States)

    Xie, Kun; Ozbay, Kaan; Kurkcu, Abdullah; Yang, Hong

    2017-08-01

    This study aims to explore the potential of using big data in advancing the pedestrian risk analysis including the investigation of contributing factors and the hotspot identification. Massive amounts of data of Manhattan from a variety of sources were collected, integrated, and processed, including taxi trips, subway turnstile counts, traffic volumes, road network, land use, sociodemographic, and social media data. The whole study area was uniformly split into grid cells as the basic geographical units of analysis. The cell-structured framework makes it easy to incorporate rich and diversified data into risk analysis. The cost of each crash, weighted by injury severity, was assigned to the cells based on the relative distance to the crash site using a kernel density function. A tobit model was developed to relate grid-cell-specific contributing factors to crash costs that are left-censored at zero. The potential for safety improvement (PSI) that could be obtained by using the actual crash cost minus the cost of "similar" sites estimated by the tobit model was used as a measure to identify and rank pedestrian crash hotspots. The proposed hotspot identification method takes into account two important factors that are generally ignored, i.e., injury severity and effects of exposure indicators. Big data, on the one hand, enable more precise estimation of the effects of risk factors by providing richer data for modeling, and on the other hand, enable large-scale hotspot identification with higher resolution than conventional methods based on census tracts or traffic analysis zones. © 2017 Society for Risk Analysis.

  18. The potential of shifting recombination hotspots to increase genetic gain in livestock breeding.

    Science.gov (United States)

    Gonen, Serap; Battagin, Mara; Johnston, Susan E; Gorjanc, Gregor; Hickey, John M

    2017-07-04

    This study uses simulation to explore and quantify the potential effect of shifting recombination hotspots on genetic gain in livestock breeding programs. We simulated three scenarios that differed in the locations of quantitative trait nucleotides (QTN) and recombination hotspots in the genome. In scenario 1, QTN were randomly distributed along the chromosomes and recombination was restricted to occur within specific genomic regions (i.e. recombination hotspots). In the other two scenarios, both QTN and recombination hotspots were located in specific regions, but differed in whether the QTN occurred outside of (scenario 2) or inside (scenario 3) recombination hotspots. We split each chromosome into 250, 500 or 1000 regions per chromosome of which 10% were recombination hotspots and/or contained QTN. The breeding program was run for 21 generations of selection, after which recombination hotspot regions were kept the same or were shifted to adjacent regions for a further 80 generations of selection. We evaluated the effect of shifting recombination hotspots on genetic gain, genetic variance and genic variance. Our results show that shifting recombination hotspots reduced the decline of genetic and genic variance by releasing standing allelic variation in the form of new allele combinations. This in turn resulted in larger increases in genetic gain. However, the benefit of shifting recombination hotspots for increased genetic gain was only observed when QTN were initially outside recombination hotspots. If QTN were initially inside recombination hotspots then shifting them decreased genetic gain. Shifting recombination hotspots to regions of the genome where recombination had not occurred for 21 generations of selection (i.e. recombination deserts) released more of the standing allelic variation available in each generation and thus increased genetic gain. However, whether and how much increase in genetic gain was achieved by shifting recombination hotspots depended

  19. In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites

    DEFF Research Database (Denmark)

    Grey, Corinne; Clément, Julie A.J.; Buard, Jérôme

    2017-01-01

    In mouse and human meiosis, DNA double-strand breaks (DSBs) initiate homologous recombination and occur at specific sites called hotspots. The localization of these sites is determined by the sequence-specific DNA binding domain of the PRDM9 histone methyl transferase. Here, we performed...

  20. Biodiversity hotspots through time: an introduction.

    Science.gov (United States)

    Willis, Katherine J; Gillson, Lindsey; Knapp, Sandra

    2007-02-28

    International targets set for reducing the rate of biodiversity loss--the 2010 target--and ensuring environmental stability (Millennium Development Goals) have helped to focus the efforts of the scientific community on providing the data necessary for their implementation. The urgency of these goals, coupled with the increased rate of habitat alteration worldwide, has meant that actions have largely not taken into account the increasing body of data about the biodiversity change in the past. We know a lot about how our planet has been altered and recovered in the past, both in deep time and through prehistory. Linking this knowledge to conservation action has not been widely practised, by either the palaeoecology or the conservation communities. Long-term data, however, have much to offer current conservation practice, and in the papers for this volume we have tried to bring together a variety of different perspectives as to how this might happen in the most effective way. We also identify areas for productive collaboration and some key synergies for work in the near future to enable our knowledge of the past to be used for conservation action in the here and now. Lateral thinking, across knowledge systems and with open-mindness about bridging data gaps, will be necessary for our accumulating knowledge about our planet's past to be brought to bear on our attempts to conserve it in the future.

  1. Bioquality Hotspots in the Tropical African Flora.

    Science.gov (United States)

    Marshall, Cicely A M; Wieringa, Jan J; Hawthorne, William D

    2016-12-05

    Identifying areas of high biodiversity is an established way to prioritize areas for conservation [1-3], but global approaches have been criticized for failing to render global biodiversity value at a scale suitable for local management [4-6]. We assembled 3.1 million species distribution records for 40,401 vascular plant species of tropical Africa from sources including plot data, herbarium databases, checklists, and the Global Biodiversity Information Facility (GBIF) and cleaned the records for geographic accuracy and taxonomic consistency. We summarized the global ranges of tropical African plant species into four weighted categories of global rarity called Stars. We applied the Star weights to summaries of species distribution data at fine resolutions to map the bioquality (range-restricted global endemism) of areas [7]. We generated confidence intervals around bioquality scores to account for the remaining uncertainty in the species inventory. We confirm the broad significance of the Horn of Africa, Guinean forests, coastal forests of East Africa, and Afromontane regions for plant biodiversity but also reveal the variation in bioquality within these broad regions and others, particularly at local scales. Our framework offers practitioners a quantitative, scalable, and replicable approach for measuring the irreplaceability of particular local areas for global biodiversity conservation and comparing those areas within their global and regional context. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Measuring the attractiveness of Dutch landscapes: identifying national hotspots using Google Maps

    NARCIS (Netherlands)

    De Vries, Sjerp; Buijs, Arjen; Langers, Fransje; Farjon, H.; van Hinsberg, Arjen; Sijtsma, Frans

    2013-01-01

    In a Cost-Benefit Analysis (CBA) or an Environmental Impact Assessment (EIA), determining the value that the general public attaches to a landscape is often problematic. To aid the inclusion of this social value in such analyses, a Google Maps-based tool, called the HotSpotMonitor (HSM), was

  3. A geostatistical approach to identify and mitigate agricultural nitrous oxide emission hotspots

    Science.gov (United States)

    Anthropogenic emissions of nitrous oxide (N2O), a trace gas with severe environmental costs, are greatest from agricultural soils amended with nitrogen (N) fertilizer. However, accurate N2O emission estimates at fine spatial scales are made difficult by their high variability, which represents a cr...

  4. Intense, Pervasive and Shared Faculty Dialogue: Generating Understanding and Identifying "Hotspots" in Five Days

    Science.gov (United States)

    Janke, Emily; Holland, Barbara; Medlin, Kristin

    2016-01-01

    Once an institution has chosen to recognize and reward community-engaged scholarship in its university-wide promotion and tenure policy, what are some strategies for aligning unit and department policies as well? This chapter describes the path followed at The University of North Carolina at Greensboro to align policies across all units and…

  5. Identifying ecosystem service hotspots for targeting land degradation neutrality investments in south-eastern Africa

    NARCIS (Netherlands)

    Willemen, Louise; Crossman, Neville D.; Quatrini, Simone; Egoh, Benis; Kalaba, Felix K.; Mbilinyi, Boniface; Groot, de Dolf

    2017-01-01

    Land degradation response actions need motivated stakeholders and investments to improve land management. In this study we present methods to prioritise locations for degradation mitigation investments based on stakeholder preferences for ecosystem services. We combine participatory and spatial

  6. Identifying ecosystem service hotspots for targeting land degradation neutrality investments in south-eastern Africa

    NARCIS (Netherlands)

    Willemen, Louise; Crossman, Neville D.; Quatrini, Simone; Egoh, Benis; Kalaba, Felix K.; Mbilinyi, Boniface; de Groot, Rudolf

    2017-01-01

    Land degradation response actions need motivated stakeholders and investments to improve land management. In this study we present methods to prioritise locations for degradation mitigation investments based on stakeholder preferences for ecosystem services. We combine participatory and spatial

  7. On - road mobile source pollutant emissions : identifying hotspots and ranking roads.

    Science.gov (United States)

    2010-12-30

    A considerable amount of pollution to the air in the forms of hydrocarbons, carbon : monoxide (CO), nitrogen oxides (NOx), particulate matter (PM) and air toxics comes : from the on-road mobile sources. Estimation of the emissions of these pollutants...

  8. A suggested classification and explanation for hotspots in some powerful radio sources

    International Nuclear Information System (INIS)

    Kronberg, P.P.; Jones, T.W.

    1982-01-01

    High resolution (1''→0.1') maps of the outer complexes of some ''well formed'' powerful radio sources suggest that we can now distinguish two physically distinct types of outer hotspots. The authors denote them as type ''A'' and ''B'' and describe them as follows: Type A hotspots, occur at the outer leading edge, and have a cusp-like, or otherwise elongated shape. This strongly suggests that their shape and energy density are determined by the ram-pressure interaction between the end of a beam or momentum flux ''pipeline'', and the ambient i.g.m. Type B hotspots generally lie off the A hotspot-galaxy/QSO axis, and are also behind the Type A hotspots. In at least some cases, they are compact and have a higher minimum energy density than the outer, Type A hotspots. (Auth.)

  9. Testing the Efficacy of Global Biodiversity Hotspots for Insect Conservation: The Case of South African Katydids.

    Directory of Open Access Journals (Sweden)

    Corinna S Bazelet

    Full Text Available The use of endemism and vascular plants only for biodiversity hotspot delineation has long been contested. Few studies have focused on the efficacy of global biodiversity hotspots for the conservation of insects, an important, abundant, and often ignored component of biodiversity. We aimed to test five alternative diversity measures for hotspot delineation and examine the efficacy of biodiversity hotspots for conserving a non-typical target organism, South African katydids. Using a 1° fishnet grid, we delineated katydid hotspots in two ways: (1 count-based: grid cells in the top 10% of total, endemic, threatened and/or sensitive species richness; vs. (2 score-based: grid cells with a mean value in the top 10% on a scoring system which scored each species on the basis of its IUCN Red List threat status, distribution, mobility and trophic level. We then compared katydid hotspots with each other and with recognized biodiversity hotspots. Grid cells within biodiversity hotspots had significantly higher count-based and score-based diversity than non-hotspot grid cells. There was a significant association between the three types of hotspots. Of the count-based measures, endemic species richness was the best surrogate for the others. However, the score-based measure out-performed all count-based diversity measures. Species richness was the least successful surrogate of all. The strong performance of the score-based method for hotspot prediction emphasizes the importance of including species' natural history information for conservation decision-making, and is easily adaptable to other organisms. Furthermore, these results add empirical support for the efficacy of biodiversity hotspots in conserving non-target organisms.

  10. Temperature dependence of the current to sustain a normal hotspot in superconducting microbridges

    International Nuclear Information System (INIS)

    Yamaguchi, Y.; Ishii, C.

    1981-01-01

    A modification of the boundary condition to determine the SN boundary in the hotspot model of superconducting microbridges is proposed and successfully applied to the interpretation of recent measurements of the hotspot-sustaining current by Mizuno and Aomine. It is shown that suppression of the order parameter due to the applied current gives rise to an additional temperature dependence of the hotspot-sustaining current in the extreme vicinity of the transition temperature. (orig.)

  11. Testing the Efficacy of Global Biodiversity Hotspots for Insect Conservation: The Case of South African Katydids.

    Science.gov (United States)

    Bazelet, Corinna S; Thompson, Aileen C; Naskrecki, Piotr

    2016-01-01

    The use of endemism and vascular plants only for biodiversity hotspot delineation has long been contested. Few studies have focused on the efficacy of global biodiversity hotspots for the conservation of insects, an important, abundant, and often ignored component of biodiversity. We aimed to test five alternative diversity measures for hotspot delineation and examine the efficacy of biodiversity hotspots for conserving a non-typical target organism, South African katydids. Using a 1° fishnet grid, we delineated katydid hotspots in two ways: (1) count-based: grid cells in the top 10% of total, endemic, threatened and/or sensitive species richness; vs. (2) score-based: grid cells with a mean value in the top 10% on a scoring system which scored each species on the basis of its IUCN Red List threat status, distribution, mobility and trophic level. We then compared katydid hotspots with each other and with recognized biodiversity hotspots. Grid cells within biodiversity hotspots had significantly higher count-based and score-based diversity than non-hotspot grid cells. There was a significant association between the three types of hotspots. Of the count-based measures, endemic species richness was the best surrogate for the others. However, the score-based measure out-performed all count-based diversity measures. Species richness was the least successful surrogate of all. The strong performance of the score-based method for hotspot prediction emphasizes the importance of including species' natural history information for conservation decision-making, and is easily adaptable to other organisms. Furthermore, these results add empirical support for the efficacy of biodiversity hotspots in conserving non-target organisms.

  12. 40 CFR 93.123 - Procedures for determining localized CO, PM10, and PM2.5 concentrations (hot-spot analysis).

    Science.gov (United States)

    2010-07-01

    ... CO, PM10, and PM2.5 concentrations (hot-spot analysis). 93.123 Section 93.123 Protection of... concentrations (hot-spot analysis). (a) CO hot-spot analysis. (1) The demonstrations required by § 93.116... make a categorical hot-spot finding that (93.116(a) is met without further hot-spot analysis for any...

  13. Detecting Malaria Hotspots: A Comparison of Rapid Diagnostic Test, Microscopy, and Polymerase Chain Reaction.

    Science.gov (United States)

    Mogeni, Polycarp; Williams, Thomas N; Omedo, Irene; Kimani, Domtila; Ngoi, Joyce M; Mwacharo, Jedida; Morter, Richard; Nyundo, Christopher; Wambua, Juliana; Nyangweso, George; Kapulu, Melissa; Fegan, Gregory; Bejon, Philip

    2017-11-27

    Malaria control strategies need to respond to geographical hotspots of transmission. Detection of hotspots depends on the sensitivity of the diagnostic tool used. We conducted cross-sectional surveys in 3 sites within Kilifi County, Kenya, that had variable transmission intensities. Rapid diagnostic test (RDT), microscopy, and polymerase chain reaction (PCR) were used to detect asymptomatic parasitemia, and hotspots were detected using the spatial scan statistic. Eight thousand five hundred eighty-one study participants were surveyed in 3 sites. There were statistically significant malaria hotspots by RDT, microscopy, and PCR for all sites except by microscopy in 1 low transmission site. Pooled data analysis of hotspots by PCR overlapped with hotspots by microscopy at a moderate setting but not at 2 lower transmission settings. However, variations in degree of overlap were noted when data were analyzed by year. Hotspots by RDT were predictive of PCR/microscopy at the moderate setting, but not at the 2 low transmission settings. We observed long-term stability of hotspots by PCR and microscopy but not RDT. Malaria control programs may consider PCR testing to guide asymptomatic malaria hotspot detection once the prevalence of infection falls. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  14. Automated Selection of Hotspots (ASH): enhanced automated segmentation and adaptive step finding for Ki67 hotspot detection in adrenal cortical cancer.

    Science.gov (United States)

    Lu, Hao; Papathomas, Thomas G; van Zessen, David; Palli, Ivo; de Krijger, Ronald R; van der Spek, Peter J; Dinjens, Winand N M; Stubbs, Andrew P

    2014-11-25

    In prognosis and therapeutics of adrenal cortical carcinoma (ACC), the selection of the most active areas in proliferative rate (hotspots) within a slide and objective quantification of immunohistochemical Ki67 Labelling Index (LI) are of critical importance. In addition to intratumoral heterogeneity in proliferative rate i.e. levels of Ki67 expression within a given ACC, lack of uniformity and reproducibility in the method of quantification of Ki67 LI may confound an accurate assessment of Ki67 LI. We have implemented an open source toolset, Automated Selection of Hotspots (ASH), for automated hotspot detection and quantification of Ki67 LI. ASH utilizes NanoZoomer Digital Pathology Image (NDPI) splitter to convert the specific NDPI format digital slide scanned from the Hamamatsu instrument into a conventional tiff or jpeg format image for automated segmentation and adaptive step finding hotspots detection algorithm. Quantitative hotspot ranking is provided by the functionality from the open source application ImmunoRatio as part of the ASH protocol. The output is a ranked set of hotspots with concomitant quantitative values based on whole slide ranking. We have implemented an open source automated detection quantitative ranking of hotspots to support histopathologists in selecting the 'hottest' hotspot areas in adrenocortical carcinoma. To provide wider community easy access to ASH we implemented a Galaxy virtual machine (VM) of ASH which is available from http://bioinformatics.erasmusmc.nl/wiki/Automated_Selection_of_Hotspots . The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_216.

  15. Validation of Hotspots Detected by Satellites in Sentinel Asia

    Science.gov (United States)

    Kaku, K.; Kushida, K.; Fukuda, M.

    2008-12-01

    The Sentinel Asia (SA) initiative is a collaboration between space agencies and disaster management agencies, applying remote sensing and Web-GIS technologies to assist disaster management in the Asia- Pacific region. It aims to: "EImprove safety in society by ICT and space technology "EImprove speed and accuracy of disaster preparedness and early warning "EMinimize the number of victims and social/economic losses. SA is a voluntary initiative led by the Asia-Pacific Regional Space Agency Forum (APRSAF) to share disaster information in near-real-time across the Asia-Pacific region. Wildfire is a major and recurring phenomenon that has a serious impact on property and human health, affecting many countries in the Asia region. Compared to other disasters in the area, it does not necessarily cause many immediate fatalities. However, it causes serious impact on property and human health due to smoke. Furthermore, its effects are of great relevance both at a regional and global level, and accordingly bear substantial influence on global warming. Responding to requirements from Asian countries, under Sentinel Asia a dedicated Wildfire Working Group (WG) has been established to apply remote sensing technology to the management of wildfire. Having accurate information on the location and intensity of the fires, and subsequent control of wildfire, are therefore very important and urgent tasks across the region. SA primarily addresses the issue of near-real-time information distribution on wildfires in the region. Concerning hotspot data obtained by satellites, it is essential to validate and improve its accuracy. In the framework of Sentinel Asia Wildfire WG, various approaches to hotspot detection, including MOD14 algorithm for MODIS hotspots, were studied, and their validations were carried out, comparing them with active fires extracted from satellite imagery and ground truth data in Chiengmai, Thailand and in Kalimantan, Indonesia.

  16. Hotspots of climate change impacts in sub-Saharan Africa and implications for adaptation and development.

    Science.gov (United States)

    Müller, Christoph; Waha, Katharina; Bondeau, Alberte; Heinke, Jens

    2014-08-01

    Development efforts for poverty reduction and food security in sub-Saharan Africa will have to consider future climate change impacts. Large uncertainties in climate change impact assessments do not necessarily complicate, but can inform development strategies. The design of development strategies will need to consider the likelihood, strength, and interaction of climate change impacts across biosphere properties. We here explore the spread of climate change impact projections and develop a composite impact measure to identify hotspots of climate change impacts, addressing likelihood and strength of impacts. Overlapping impacts in different biosphere properties (e.g. flooding, yields) will not only claim additional capacity to respond, but will also narrow the options to respond and develop. Regions with severest projected climate change impacts often coincide with regions of high population density and poverty rates. Science and policy need to propose ways of preparing these areas for development under climate change impacts. © 2014 John Wiley & Sons Ltd.

  17. Coldspots and hotspots - Global tectonics and mantle dynamics of Venus

    Science.gov (United States)

    Bindschadler, Duane L.; Schubert, Gerald; Kaula, William M.

    1992-01-01

    Based on geologic observations provided by Magellan's first cycle of data collection and recent models of mantle convection in spherical shells and crustal deformation, the major topographic and geologic features of Venus are incorporated into a model of global mantle dynamics. Consideration is given to volcanic rises, such as Beta Regio and Atla Regio, plateau-shaped highlands dominated by complex ridged terrain (e.g., Ovda Regio and Alpha Regio), and circular lowland regions, such as Atalanta Planitia. Each of these features is related to either mantle plumes (hotspots) or mantle downwellings (coldspots).

  18. French Polynesia Hotspot Swells Explained By Dynamic Topography

    Science.gov (United States)

    Adam, C.; Yoshida, M.; Isse, T.; Suetsugu, D.; Shiobara, H.; Sugioka, H.; Kanazawa, T.; Fukao, Y.; Barruol, G.

    2007-12-01

    Situated on the South Pacific Superswell, French Polynesia is a region characterized by numerous geophysical anomalies among which a high volcanism concentration. Seven hotspots are required to explain the observed chains, volcanism ages and geochemical trends. Many open questions still remain on the origin of these hotspot chains: are they created by passive uplift of magma due to discontinuities in the structure of the lithosphere or by the ascent of mantle plumes? In this case, at which depth do these plumes initiate in the mantle? Many geophysical observations (bathymetry, gravity, magnetism, volcanism ages..) are used to understand the unique phenomenon occurring on this region. The most useful information may come from tomography models since they provide a 3D view of the mantle. Until recently, the tomography models over the region were quite inaccurate because of the sparse location of the seismic stations. The deployment of two new seismic stations networks (BBOBS and temporary island stations) has lately remedied this failing. The resulting tomography model obtained through the inversion of Rayleigh waves provides the most accurate view of the shallowest part of the mantle (depths ≤ 240 km) beneath French Polynesia. Indeed, for the first time the accuracy of a tomography model is good enough to provide information about plume phenomenology in this complex region. In order to quantify the plumes effect on the seafloor, we compute the dynamic topography through an instantaneous flow model. The general trend of the observed depths anomalies (highs and lows) is well recovered. For example the amplitude, location and extension of the swells associated with the Society, Macdonald and Rarotonga are accurately described by the dynamic model. We also find that dynamic uplift is associated with the Tuamotu archipelago which means that a part of the observed swell is due to the present day action of plumes. Since no volcanism ages are available over this chain

  19. Discovery of small molecules binding to the normal conformation of prion by combining virtual screening and multiple biological activity evaluation methods

    Science.gov (United States)

    Li, Lanlan; Wei, Wei; Jia, Wen-Juan; Zhu, Yongchang; Zhang, Yan; Chen, Jiang-Huai; Tian, Jiaqi; Liu, Huanxiang; He, Yong-Xing; Yao, Xiaojun

    2017-12-01

    Conformational conversion of the normal cellular prion protein, PrPC, into the misfolded isoform, PrPSc, is considered to be a central event in the development of fatal neurodegenerative diseases. Stabilization of prion protein at the normal cellular form (PrPC) with small molecules is a rational and efficient strategy for treatment of prion related diseases. However, few compounds have been identified as potent prion inhibitors by binding to the normal conformation of prion. In this work, to rational screening of inhibitors capable of stabilizing cellular form of prion protein, multiple approaches combining docking-based virtual screening, steady-state fluorescence quenching, surface plasmon resonance and thioflavin T fluorescence assay were used to discover new compounds interrupting PrPC to PrPSc conversion. Compound 3253-0207 that can bind to PrPC with micromolar affinity and inhibit prion fibrillation was identified from small molecule databases. Molecular dynamics simulation indicated that compound 3253-0207 can bind to the hotspot residues in the binding pocket composed by β1, β2 and α2, which are significant structure moieties in conversion from PrPC to PrPSc.

  20. Tlys, a newly identified Sulfolobus spindle-shaped virus 1 transcript expressed in the lysogenic state, encodes a DNA-binding protein interacting at the promoters of the early genes

    DEFF Research Database (Denmark)

    Fusco, Salvatore; She, Qunxin; Bartolucci, Simonetta

    2013-01-01

    -binding motif. DNA-binding assays demonstrated that the recombinant F55, purified from Escherichia coli, is indeed a putative transcription factor able to recognize site specifically target sequences in the promoters of the early induced T5, T6, and Tind transcripts, as well as of its own promoter. Binding...... the growth of the lysogenic host. The correponding gene f55 lies between two transcriptional units (T6 and Tind) that are upregulated upon UV irradiation. The open reading frame f55 encodes a 6.3-kDa protein which shows sequence identity with negative regulators that fold into the ribbon-helix-helix DNA....... Taking together the transcriptional analysis data and the biochemical evidences, we surmise that the protein F55 is involved in the regulation of the lysogenic state of SSV1....

  1. Use of eluted peptide sequence data to identify the binding characteristics of peptides to the insulin-dependent diabetes susceptibility allele HLA-DQ8 (DQ 3.2).

    Science.gov (United States)

    Godkin, A; Friede, T; Davenport, M; Stevanovic, S; Willis, A; Jewell, D; Hill, A; Rammensee, H G

    1997-06-01

    HLA-DQ8 (A1*0301, B1*0302) and -DQ2 (A1*0501, B1*0201) are both associated with diseases such as insulin-dependent diabetes mellitus and coeliac disease. We used the technique of pool sequencing to look at the requirements of peptides binding to HLA-DQ8, and combined these data with naturally sequenced ligands and in vitro binding assays to describe a novel motif for HLA-DQ8. The motif, which has the same basic format as many HLA-DR molecules, consists of four or five anchor regions, in the positions from the N-terminus of the binding core of n, n + 3, n + 5/6 and n + 8, i.e. P1, P4, P6/7 and P9. P1 and P9 require negative or polar residues, with mainly aliphatic residues at P4 and P6/7. The features of the HLA-DQ8 motif were then compared to a pool sequence of peptides eluted from HLA-DQ2. A consensus motif for the binding of a common peptide which may be involved in disease pathogenesis is described. Neither of the disease-associated alleles HLA-DQ2 and -DQ8 have Asp at position 57 of the beta-chain. This Asp, if present, may form a salt bridge with an Arg at position 79 of the alpha-chain and so alter the binding specificity of P9. HLA-DQ2 and -DQ8 both appear to prefer negatively charged amino acids at P9. In contrast, HLA-DQ7 (A1*0301, B1*0301), which is not associated with diabetes, has Asp at beta 57, allowing positively charged amino acids at P9. This analysis of the sequence features of DQ-binding peptides suggests molecular characteristics which may be useful to predict epitopes involved in disease pathogenesis.

  2. Hotspots of human-induced biomass productivity decline and their social-ecological types toward supporting national policy and local studies on combating land degradation

    Science.gov (United States)

    Vu, Quyet Manh; Le, Quang Bao; Vlek, Paul L. G.

    2014-10-01

    Identification and social-ecological characterization of areas that experience high levels of persistent productivity decline are essential for planning appropriate management measures. Although land degradation is mainly induced by human actions, the phenomenon is concurrently influenced by global climate changes that need to be taken into account in land degradation assessments. This study aims to delineate the geographic hotspots of human-induced land degradation in the country and classify the social-ecological characterizations of each specific degradation hotspot type. The research entailed a long-term time-series (1982-2006) of Normalized Difference Vegetation Index to specify the extents of areas with significant biomass decline or increase in Vietnam. Annual rainfall and temperature time-series were then used to separate areas of human-induced biomass productivity decline from those driven by climate dynamics. Next, spatial cluster analyses identified social-ecological types of degradation for guiding further investigations at regional and local scales. The results show that about 19% of the national land mass experienced persistent declines in biomass productivity over the last 25 years. Most of the degraded areas are found in the Southeast and Mekong River Delta (17,984 km2), Northwest Mountains (14,336 km2), and Central Highlands (13,504 km2). We identified six and five social-ecological types of degradation hotspots in agricultural and forested zones, respectively. Constraints in soil nutrient availability and nutrient retention capability are widely spreading in all degradation hotspot types. These hotspot types are different from each other in social and ecological conditions, suggesting that region-specific strategies are needed for the formulation of land degradation combating policy.

  3. The identification of 'hotspots' of heavy metal pollution in soil-rice systems at a regional scale in eastern China.

    Science.gov (United States)

    Li, Wanlu; Xu, Binbin; Song, Qiujin; Liu, Xingmei; Xu, Jianming; Brookes, Philip C

    2014-02-15

    Chinese agricultural soils and crops are suffering from increasing damage from heavy metals, which are introduced from various pollution sources including agriculture, traffic, mining and especially the flourishing private metal recycling industry. In this study, 219 pairs of rice grain and corresponding soil samples were collected from Wenling in Zhejiang Province to identify the spatial relationship and pollution hotspots of Cd, Cu, Ni and Zn in the soil-rice system. The mean soil concentrations of heavy metals were 0.316 mg kg(-1) for Cd, 47.3 mg kg(-1) for Cu, 31.7 mg kg(-1) for Ni and 131 mg kg(-1) for Zn, and the metal concentrations in rice grain were 0.132 mg kg(-1) for Cd, 2.46 mg kg(-1) for Cu, 0.223 mg kg(-1) for Ni and 17.4 mg kg(-1) for Zn. The coefficient of variability (CV) of soil Cd, Cu and rice Cd were 147%, 146% and 180%, respectively, indicating an extensive variability. While the CVs of other metals ranged from 23.4% to 84.3% with a moderate variability. Kriging interpolation procedure and the Local Moran's I index detected the locations of pollution hotspots of these four metals. Cd and Cu had a very similar spatial pattern, with contamination hotspots located simultaneously in the northwestern part of the study area, and there were obvious hotspots for soil Zn in the north area, while in the northeast for soil Ni. The existence of hotspots may be due to industrialization and other anthropogenic activities. An Enrichment Index (EI) was employed to measure the uptake of heavy metals by rice. The results indicated that the accumulation and availability of heavy metals in the soil-rice system may be influenced by both soil heavy metal concentrations and soil physico-chemical properties. Cross-correlograms quantitatively illustrated that EIs were significantly correlated with soil properties. Soil pH and organic matter were the most important factors controlling the uptake of heavy metals by rice. As results, positive measures should be taken into

  4. Detecting and confirming residual hotspots of lymphatic filariasis transmission in American Samoa 8 years after stopping mass drug administration.

    Science.gov (United States)

    Lau, Colleen L; Sheridan, Sarah; Ryan, Stephanie; Roineau, Maureen; Andreosso, Athena; Fuimaono, Saipale; Tufa, Joseph; Graves, Patricia M

    2017-09-01

    suspected hotspots, including a 9 year old child. Our results provide field evidence that integrating LF surveillance with other surveys is effective and feasible for identifying potential hotspots, and conducting surveillance at worksites provides an efficient method of sampling large populations of adults.

  5. Effects of Demographic History on the Detection of Recombination Hotspots from Linkage Disequilibrium.

    Science.gov (United States)

    Dapper, Amy L; Payseur, Bret A

    2018-02-01

    In some species, meiotic recombination is concentrated in small genomic regions. These "recombination hotspots" leave signatures in fine-scale patterns of linkage disequilibrium, raising the prospect that the genomic landscape of hotspots can be characterized from sequence variation. This approach has led to the inference that hotspots evolve rapidly in some species, but are conserved in others. Historic demographic events, such as population bottlenecks, are known to affect patterns of linkage disequilibrium across the genome, violating population genetic assumptions of this approach. Although such events are prevalent, demographic history is generally ignored when making inferences about the evolution of recombination hotspots. To determine the effect of demography on the detection of recombination hotspots, we use the coalescent to simulate haplotypes with a known recombination landscape. We measure the ability of popular linkage disequilibrium-based programs to detect hotspots across a range of demographic histories, including population bottlenecks, hidden population structure, population expansions, and population contractions. We find that demographic events have the potential to greatly reduce the power and increase the false positive rate of hotspot discovery. Neither the power nor the false positive rate of hotspot detection can be predicted without also knowing the demographic history of the sample. Our results suggest that ignoring demographic history likely overestimates the power to detect hotspots and therefore underestimates the degree of hotspot sharing between species. We suggest strategies for incorporating demographic history into population genetic inferences about recombination hotspots. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  6. A Method for Improving Hotspot Directional Signatures in BRDF Models Used for MODIS

    Science.gov (United States)

    Jiao, Ziti; Schaaf, Crystal B.; Dong, Yadong; Roman, Miguel; Hill, Michael J.; Chen, Jing M.; Wang, Zhuosen; Zhang, Hu; Saenz, Edward; Poudyal, Rajesh; hide

    2016-01-01

    The semi-empirical, kernel-driven, linear RossThick-LiSparseReciprocal (RTLSR) Bidirectional Reflectance Distribution Function (BRDF) model is used to generate the routine MODIS BRDFAlbedo product due to its global applicability and the underlying physics. A challenge of this model in regard to surface reflectance anisotropy effects comes from its underestimation of the directional reflectance signatures near the Sun illumination direction; also known as the hotspot effect. In this study, a method has been developed for improving the ability of the RTLSR model to simulate the magnitude and width of the hotspot effect. The method corrects the volumetric scattering component of the RTLSR model using an exponential approximation of a physical hotspot kernel, which recreates the hotspot magnitude and width using two free parameters (C(sub 1) and C(sub 2), respectively). The approach allows one to reconstruct, with reasonable accuracy, the hotspot effect by adjusting or using the prior values of these two hotspot variables. Our results demonstrate that: (1) significant improvements in capturing hotspot effect can be made to this method by using the inverted hotspot parameters; (2) the reciprocal nature allow this method to be more adaptive for simulating the hotspot height and width with high accuracy, especially in cases where hotspot signatures are available; and (3) while the new approach is consistent with the heritage RTLSR model inversion used to estimate intrinsic narrowband and broadband albedos, it presents some differences for vegetation clumping index (CI) retrievals. With the hotspot-related model parameters determined a priori, this method offers improved performance for various ecological remote sensing applications; including the estimation of canopy structure parameters.

  7. What, When, Where, and Why of Secondary Hawaiian Hotspot Volcanism

    Science.gov (United States)

    Garcia, M. O.; Ito, G.; Applegate, B.; Weis, D.; Swinnard, L.; Flinders, A.; Hanano, D.; Nobre-Silva, I.; Bianco, T.; Naumann, T.; Geist, D.; Blay, C.; Sciaroni, L.; Maerschalk, C.; Harpp, K.; Christensen, B.

    2007-12-01

    Secondary hotspot volcanism occurs on most oceanic island groups (Hawaii, Canary, Society) but its origins remain enigmatic. A 28-day marine expedition used multibeam bathymetry and acoustic imagery to map the extent of submarine volcanic fields around the northern Hawaiian Islands (Kauai, Niihau and Kaula), and the JASON2 ROV to sample many volcanoes to characterize the petrology, geochemistry (major and trace elements, and isotopes) and ages of the lavas from these volcanoes. Our integrated geological, geochemical and geophysical study attempts to examine the what (compositions and source), where (distribution and volumes), when (ages), and why (mechanisms) of secondary volcanism on and around the northern Hawaiian Islands. A first-order objective was to establish how the submarine volcanism relates in space, time, volume, and composition to the nearby shield volcanoes and their associated onshore secondary volcanism. Our surveying and sampling revealed major fields of submarine volcanoes extending from the shallow slopes of these islands to more than 100 km offshore. These discoveries dramatically expand the volumetric importance, distribution and geodynamic framework for Hawaiian secondary volcanism. New maps and rock petrology on the samples collected will be used to evaluate currently proposed mechanisms for secondary volcanism and to consider new models such as small-scale mantle convection driven by thermal and melt-induced buoyancy to produce the huge volume of newly discovered lava. Our results seem to indicate substantial revisions are needed to our current perceptions of hotspot dynamics for Hawaii and possibly elsewhere.

  8. Hot-Spot Ignition Mechanisms for Explosives and Propellants

    Science.gov (United States)

    Field, J. E.; Bourne, N. K.; Palmer, S. J. P.; Walley, S. M.

    1992-05-01

    This paper describes the response of explosives to stress and impact and in particular the mechanisms of `hot-spot' production. Samples in the form of single crystals, powder layers, pressed pellets, gels, polymer bonded explosives (PBXs) and propellants have been studied. Techniques used include a drop-weight facility with transparent anvils which allows photography at microsecond framing intervals, an instrumented drop-weight machine, a miniaturized Hopkinson bar system for high strain rate property measurement, laser speckle for studying the deformation and fracture of PBXs, an automated system for analysing speckle patterns and heat sensitive film for recording the positions and temperatures of hot spots. Polishing and staining methods have been developed to observe the microstructure of PBXs and failure during quasi-static loading. Ignition, when it occurred, took place at local hot-spot sites. Evidence is discussed for a variety of ignition mechanisms including adiabatic shear of the explosive, adiabatic heating of trapped gases during cavity collapse, viscous flow, friction, fracture and shear of added particles and triboluminescent discharge.

  9. Biodiversity hotspots: A shortcut for a more complicated concept

    Directory of Open Access Journals (Sweden)

    Christian Marchese

    2015-01-01

    Full Text Available In an era of human activities, global environmental changes, habitat loss and species extinction, conservation strategies are a crucial step toward minimizing biodiversity loss. For instance, oceans acidification and land use are intensifying in many places with negative and often irreversible consequences for biodiversity. Biodiversity hotspots, despite some criticism, have become a tool for setting conservation priorities and play an important role in decision-making for cost-effective strategies to preserve biodiversity in terrestrial and, to some extent, marine ecosystems. This area-based approach can be applied to any geographical scale and it is considered to be one of the best approaches for maintaining a large proportion of the world’s biological diversity. However, delineating hotspots includes quantitative criteria along with subjective considerations and the risk is to neglect areas, such as coldspots, with other types of conservation value. Nowadays, it is widely acknowledged that biodiversity is much more than just the number of species in a region and a conservation strategy cannot be based merely on the number of taxa present in an ecosystem. Therefore, the idea that strongly emerges is the need to reconsider conservation priorities and to go toward an interdisciplinary approach through the creation of science-policy partnerships.

  10. Lack of visible change around active hotspots on Io

    Science.gov (United States)

    1996-01-01

    Detail of changes around two hotspots on Jupiter's moon Io as seen by Voyager 1 in April 1979 (left) and NASA's Galileo spacecraft on September 7th, 1996 (middle and right). The right frame was created with images from the Galileo Solid State Imaging system's near-infrared (756 nm), green, and violet filters. For better comparison, the middle frame mimics Voyager colors. The calderas at the top and at the lower right of the images correspond to the locations of hotspots detected by the Near Infrared Mapping Spectrometer aboard the Galileo spacecraft during its second orbit. There are no significant morphologic changes around these hot calderas; however, the diffuse red deposits, which are simply dark in the Voyager colors, appear to be associated with recent and/or ongoing volcanic activity. The three calderas range in size from approximately 100 kilometers to approximately 150 kilometers in diameter. The caldera in the lower right of each frame is named Malik. North is to the top of all frames.The Jet Propulsion Laboratory, Pasadena, CA manages the Galileo mission for NASA's Office of Space Science, Washington, DC. JPL is an operating division of California Institute of Technology (Caltech).This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://galileo.jpl.nasa.gov. Background information and educational context for the images can be found at URL http://www.jpl.nasa.gov/galileo/sepo

  11. Are splash plumes the origin of minor hotspots?

    Science.gov (United States)

    Davies, J. H.; Bunge, H.-P.

    2006-05-01

    It has been claimed that focused hot cylindrical upwelling plumes cause many of the surface volcanic hotspots on Earth. It has also been argued that they must originate from thermal boundary layers. In this paper, we present spherical simulations of mantle circulation at close to Earth-like vigor with significant internal heating. These show, in addition to thermal boundary layer plumes, a new class of plumes that are not rooted in thermal boundary layers. These plumes develop as instabilities from the edge of bowls of hot mantle, which are produced by cold downwelling material deforming hot sheets of mantle. The resulting bowl and plume structure can look a bit like the “splash” of a water droplet. These splash plumes might provide an explanation for some hotspots that are not underlain by thermal boundary layer sourced plumes and not initiated by large igneous provinces. We suggest that in Earth's mantle, lithospheric instabilities or small pieces of subducting slab could play the role of the model downwelling material in initiating splash plumes. Splash plumes would have implications for interpreting ocean-island basalt geochemistry, plume fixity, excess plume temperature, and estimating core heat flux. Improved seismic imaging will ultimately test this hypothesis.

  12. Chronic kidney disease hotspots in developing countries in South Asia.

    Science.gov (United States)

    Abraham, Georgi; Varughese, Santosh; Thandavan, Thiagarajan; Iyengar, Arpana; Fernando, Edwin; Naqvi, S A Jaffar; Sheriff, Rezvi; Ur-Rashid, Harun; Gopalakrishnan, Natarajan; Kafle, Rishi Kumar

    2016-02-01

    In many developing countries in the South Asian region, screening for chronic diseases in the community has shown a widely varying prevalence. However, certain geographical regions have shown a high prevalence of chronic kidney disease (CKD) of unknown etiology. This predominantly affects the young and middle-aged population with a lower socioeconomic status. Here, we describe the hotspots of CKD of undiagnosed etiology in South Asian countries including the North, Central and Eastern provinces of Sri Lanka and the coastal region of the state of Andhra Pradesh in India. Screening of these populations has revealed cases of CKD in various stages. Race has also been shown to be a factor, with a much lower prevalence of CKD in whites compared to Asians, which could be related to the known influence of ethnicity on CKD development as well as environmental factors. The difference between developed and developing nations is most stark in the realm of healthcare, which translates into CKD hotspots in many regions of South Asian countries. Additionally, the burden of CKD stage G5 remains unknown due to the lack of registry reports, poor access to healthcare and lack of an organized chronic disease management program. The population receiving various forms of renal replacement therapy has dramatically increased in the last decade due to better access to point of care, despite the disproportionate increase in nephrology manpower. In this article we will discuss the nephrology care provided in various countries in South Asia, including India, Bangladesh, Pakistan, Nepal, Bhutan, Sri Lanka and Afghanistan.

  13. Tectonics, climate, and the rise and demise of continental aquatic species richness hotspots.

    Science.gov (United States)

    Neubauer, Thomas A; Harzhauser, Mathias; Georgopoulou, Elisavet; Kroh, Andreas; Mandic, Oleg

    2015-09-15

    Continental aquatic species richness hotspots are unevenly distributed across the planet. In present-day Europe, only two centers of biodiversity exist (Lake Ohrid on the Balkans and the Caspian Sea). During the Neogene, a wide variety of hotspots developed in a series of long-lived lakes. The mechanisms underlying the presence of richness hotspots in different geological periods have not been properly examined thus far. Based on Miocene to Recent gastropod distributions, we show that the existence and evolution of such hotspots in inland-water systems are tightly linked to the geodynamic history of the European continent. Both past and present hotspots are related to the formation and persistence of long-lived lake systems in geological basins or to isolation of existing inland basins and embayments from the marine realm. The faunal evolution within hotspots highly depends on warm climates and surface area. During the Quaternary icehouse climate and extensive glaciations, limnic biodiversity sustained a severe decline across the continent and most former hotspots disappeared. The Recent gastropod distribution is mainly a geologically young pattern formed after the Last Glacial Maximum (19 ky) and subsequent formation of postglacial lakes. The major hotspots today are related to long-lived lakes in preglacially formed, permanently subsiding geological basins.

  14. Biodiversity hotspots on the Dutch Continental Shelf: a marine strategy framework directive perspective

    NARCIS (Netherlands)

    Bos, O.G.; Witbaard, R.; Lavaleye, M.S.S.; Moorsel, G.W.N.M.; Teal, L.R.; Hal, van R.; Hammen, van der T.; Hofstede, ter R.; Bemmelen, van R.S.A.; Witte, R.H.; Geelhoed, S.C.V.; Dijkman, E.M.

    2011-01-01

    This report presenst hotspots of biodiversity for benthos, fish, birds, marine mammals and habitats on the Dutch Continental Shelf. These hotspots are based on a spatial application of biodiversity metrics developed in this study for the GES(Good Environmental Status)-descriptor 1 ‘Biological

  15. DNA Sequence-Mediated, Evolutionarily Rapid Redistribution of Meiotic Recombination Hotspots

    Science.gov (United States)

    Wahls, Wayne P.; Davidson, Mari K.

    2011-01-01

    Hotspots regulate the position and frequency of Spo11 (Rec12)-initiated meiotic recombination, but paradoxically they are suicidal and are somehow resurrected elsewhere in the genome. After the DNA sequence-dependent activation of hotspots was discovered in fission yeast, nearly two decades elapsed before the key realizations that (A) DNA site-dependent regulation is broadly conserved and (B) individual eukaryotes have multiple different DNA sequence motifs that activate hotspots. From our perspective, such findings provide a conceptually straightforward solution to the hotspot paradox and can explain other, seemingly complex features of meiotic recombination. We describe how a small number of single-base-pair substitutions can generate hotspots de novo and dramatically alter their distribution in the genome. This model also shows how equilibrium rate kinetics could maintain the presence of hotspots over evolutionary timescales, without strong selective pressures invoked previously, and explains why hotspots localize preferentially to intergenic regions and introns. The model is robust enough to account for all hotspots of humans and chimpanzees repositioned since their divergence from the latest common ancestor. PMID:22084420

  16. Hotspots in trauma memories and their relationship to successful trauma-focused psychotherapy: a pilot study.

    Science.gov (United States)

    Nijdam, Mirjam J; Baas, Melanie A M; Olff, Miranda; Gersons, Berthold P R

    2013-02-01

    Imaginal exposure is an essential element of trauma-focused psychotherapies for posttraumatic stress disorder (PTSD). Exposure should in particular focus on the "hotspots," the parts of trauma memories that cause high levels of emotional distress which are often reexperienced. Our aim was to investigate whether differences in the focus on hotspots differentiate between successful and unsuccessful trauma-focused psychotherapies. As part of a randomized trial, 45 PTSD patients completed brief eclectic psychotherapy for PTSD. We retrospectively assessed audio recordings of therapy sessions of 20 patients. Frequency of hotspots and the associated emotions, cognitions, and characteristics were compared for the most successful (n = 10) versus the least successful (n = 10) treatments. The mean number of unique hotspots per patient was 3.20, and this number did not differ between successful and unsuccessful treatments. In successful treatments, however, hotspots were more frequently addressed (r = .48), and they were accompanied by more characteristics of hotspots (r = .39), such as an audible change in affect, indicating medium- to large-sized effects. Repeatedly focusing on hotspots and looking for associated characteristics of hotspots may help clinicians to enhance the efficacy of imaginal exposure for patients who would otherwise show insufficient response to treatment. Copyright © 2013 International Society for Traumatic Stress Studies.

  17. The Meiotic Recombination Activator PRDM9 Trimethylates Both H3K36 and H3K4 at Recombination Hotspots In Vivo.

    Science.gov (United States)

    Powers, Natalie R; Parvanov, Emil D; Baker, Christopher L; Walker, Michael; Petkov, Petko M; Paigen, Kenneth

    2016-06-01

    In many mammals, including humans and mice, the zinc finger histone methyltransferase PRDM9 performs the first step in meiotic recombination by specifying the locations of hotspots, the sites of genetic recombination. PRDM9 binds to DNA at hotspots through its zinc finger domain and activates recombination by trimethylating histone H3K4 on adjacent nucleosomes through its PR/SET domain. Recently, the isolated PR/SET domain of PRDM9 was shown capable of also trimethylating H3K36 in vitro, raising the question of whether this reaction occurs in vivo during meiosis, and if so, what its function might be. Here, we show that full-length PRDM9 does trimethylate H3K36 in vivo in mouse spermatocytes. Levels of H3K4me3 and H3K36me3 are highly correlated at hotspots, but mutually exclusive elsewhere. In vitro, we find that although PRDM9 trimethylates H3K36 much more slowly than it does H3K4, PRDM9 is capable of placing both marks on the same histone molecules. In accord with these results, we also show that PRDM9 can trimethylate both K4 and K36 on the same nucleosomes in vivo, but the ratio of K4me3/K36me3 is much higher for the pair of nucleosomes adjacent to the PRDM9 binding site compared to the next pair further away. Importantly, H3K4me3/H3K36me3-double-positive nucleosomes occur only in regions of recombination: hotspots and the pseudoautosomal (PAR) region of the sex chromosomes. These double-positive nucleosomes are dramatically reduced when PRDM9 is absent, showing that this signature is PRDM9-dependent at hotspots; the residual double-positive nucleosomes most likely come from the PRDM9-independent PAR. These results, together with the fact that PRDM9 is the only known mammalian histone methyltransferase with both H3K4 and H3K36 trimethylation activity, suggest that trimethylation of H3K36 plays an important role in the recombination process. Given the known requirement of H3K36me3 for double strand break repair by homologous recombination in somatic cells, we

  18. Causes of plant diversification in the Cape biodiversity hotspot of South Africa.

    Science.gov (United States)

    Schnitzler, Jan; Barraclough, Timothy G; Boatwright, James S; Goldblatt, Peter; Manning, John C; Powell, Martyn P; Rebelo, Tony; Savolainen, Vincent

    2011-05-01

    The Cape region of South Africa is one of the most remarkable hotspots of biodiversity with a flora comprising more than 9000 plant species, almost 70% of which are endemic, within an area of only ± 90,000 km2. Much of the diversity is due to an exceptionally large contribution of just a few clades that radiated substantially within this region, but little is known about the causes of these radiations. Here, we present a comprehensive analysis of plant diversification, using near complete species-level phylogenies of four major Cape clades (more than 470 species): the genus Protea, a tribe of legumes (Podalyrieae) and two speciose genera within the iris family (Babiana and Moraea), representing three of the seven largest plant families in this biodiversity hotspot. Combining these molecular phylogenetic data with ecological and biogeographical information, we tested key hypotheses that have been proposed to explain the radiation of the Cape flora. Our results show that the radiations started throughout the Oligocene and Miocene and that net diversification rates have remained constant through time at globally moderate rates. Furthermore, using sister-species comparisons to assess the impact of different factors on speciation, we identified soil type shifts as the most important cause of speciation in Babiana, Moraea, and Protea, whereas shifts in fire-survival strategy is the most important factor for Podalyrieae. Contrary to previous findings in other groups, such as orchids, pollination syndromes show a high degree of phylogenetic conservatism, including groups with a large number of specialized pollination syndromes like Moraea. We conclude that the combination of complex environmental conditions together with relative climatic stability promoted high speciation and/or low extinction rates as the most likely scenario leading to present-day patterns of hyperdiversity in the Cape.

  19. Spatial-Temporal Hotspot Pattern Analysis of Provincial Environmental Pollution Incidents and Related Regional Sustainable Management in China in the Period 1995–2012

    Directory of Open Access Journals (Sweden)

    Lei Ding

    2015-10-01

    Full Text Available Spatial-temporal hotspot pattern analysis of environmental pollution incidents provides an indispensable source of information for the further development of incident prevention measures. In this study, the spatial-temporal patterns of environmental pollution incidents in China in the period of 1995–2012 were analyzed, using the Spatial Getis-Ord statistic and an Improved Prediction Accuracy Index (IAPI. The results show that, in this period, the occurrence of environmental incidents exhibited a dynamic growth pattern but then dropped and continued to drop after the year 2006, which was considered a crucial turning point. Not coincidentally, this corresponds to the year when the State Council issued its National Environmental Emergency Plan, and following the examination of major incidents, special actions were taken to strengthen the control of incidents and emergency responses. The results from Getis-Ord General G statistical analysis show that the spatial agglomeration phenomenon was statistically significant after 1999 and that the level of spatial agglomeration was rising, while the Getis-Ord Gi* statistical analysis reveals that environmental pollution incidents were mainly agglomerated in the Pan Yangtze River Delta and Pan Pearl River Delta regions. Accordingly, the spatial-temporal hotspot pattern based on the IAPI values at the provincial scale could be categorized into: stable hotspots, unstable hotspots, and cold-spot areas. The stable hotspots category was further divided into three subtypes: industrial distribution type, industrial transfer type, and extensive economic growth type. Finally, the corresponding measures for sustainable management were proposed: stable hotspots were classified as essential regions requiring the immediate prevention and control of environmental pollution incidents; unstable hotspots were characterized by their need for ongoing and continual prevention measures, and cold-spots were those areas that

  20. Structured association analysis leads to insight into Saccharomyces cerevisiae gene regulation by finding multiple contributing eQTL hotspots associated with functional gene modules.

    Science.gov (United States)

    Curtis, Ross E; Kim, Seyoung; Woolford, John L; Xu, Wenjie; Xing, Eric P

    2013-03-21

    , we provide experimental evidence suggesting that the identified candidates do regulate the target genes predicted by GFlasso. Thus, this structured association analysis of a yeast eQTL dataset via GFlasso, coupled with extensive bioinformatics analysis, discovers a novel regulation pattern between multiple eQTL hotspots and functional gene modules. Furthermore, this analysis demonstrates the potential of GFlasso as a powerful computational tool for eQTL studies that exploit the rich structural information among expression traits due to correlation, regulation, or other forms of biological dependencies.

  1. Paleo-drainage basin connectivity predicts evolutionary relationships across three Southeast Asian biodiversity hotspots.

    Science.gov (United States)

    de Bruyn, Mark; Rüber, Lukas; Nylinder, Stephan; Stelbrink, Björn; Lovejoy, Nathan R; Lavoué, Sébastien; Tan, Heok Hui; Nugroho, Estu; Wowor, Daisy; Ng, Peter K L; Siti Azizah, M N; Von Rintelen, Thomas; Hall, Robert; Carvalho, Gary R

    2013-05-01

    Understanding factors driving diversity across biodiversity hotspots is critical for formulating conservation priorities in the face of ongoing and escalating environmental deterioration. While biodiversity hotspots encompass a small fraction of Earth's land surface, more than half the world's plants and two-thirds of terrestrial vertebrate species are endemic to these hotspots. Tropical Southeast (SE) Asia displays extraordinary species richness, encompassing four biodiversity hotspots, though disentangling multiple potential drivers of species richness is confounded by the region's dynamic geological and climatic history. Here, we use multilocus molecular genetic data from dense multispecies sampling of freshwater fishes across three biodiversity hotspots, to test the effect of Quaternary climate change and resulting drainage rearrangements on aquatic faunal diversification. While Cenozoic geological processes have clearly shaped evolutionary history in SE Asian halfbeak fishes, we show that paleo-drainage re-arrangements resulting from Quaternary climate change played a significant role in the spatiotemporal evolution of lowland aquatic taxa, and provide priorities for conservation efforts.

  2. Diagnostic for determining the mix in inertial confinement fusion capsule hotspot

    Energy Technology Data Exchange (ETDEWEB)

    He, Shibei; Ding, Yongkun, E-mail: ding-yk@vip.sina.com; Miao, Wenyong; Zhang, Xing; Tu, Shaoyong; Yuan, Yongteng; Pu, Yudong; Yan, Ji; Wei, Minxi; Yin, Chuansheng [Research Center of Laser Fusion, China Academy of Engineering Physics, Mianyang 621900 (China)

    2016-07-15

    A diagnostic is developed for determining the hotspot mix in inertial confinement fusion experiments. A multi-channel pinhole camera measures Bremsstrahlung emissions from implosion capsules ranging from 6 keV to 30 keV and records an image of the hotspot. Meanwhile, a planar crystal spectrometer measures Ar line emissions used to deduce the electron density of the hotspot. An X-ray streaked camera records the burn duration. With the Bremsstrahlung spectrum, electron density, hotspot volume, and burn duration, the mix quantity is determined by solving a pair of linear equations. This inferred mix amount has an uncertainty due to the uncertainty of the electron density, but with the help of the measured neutron product, the most likely mix quantity value can be determined. This technique is applied to experimental images to infer the quantity of CH ablator mix into the hotspot.

  3. Diagnostic for determining the mix in inertial confinement fusion capsule hotspot

    International Nuclear Information System (INIS)

    He, Shibei; Ding, Yongkun; Miao, Wenyong; Zhang, Xing; Tu, Shaoyong; Yuan, Yongteng; Pu, Yudong; Yan, Ji; Wei, Minxi; Yin, Chuansheng

    2016-01-01

    A diagnostic is developed for determining the hotspot mix in inertial confinement fusion experiments. A multi-channel pinhole camera measures Bremsstrahlung emissions from implosion capsules ranging from 6 keV to 30 keV and records an image of the hotspot. Meanwhile, a planar crystal spectrometer measures Ar line emissions used to deduce the electron density of the hotspot. An X-ray streaked camera records the burn duration. With the Bremsstrahlung spectrum, electron density, hotspot volume, and burn duration, the mix quantity is determined by solving a pair of linear equations. This inferred mix amount has an uncertainty due to the uncertainty of the electron density, but with the help of the measured neutron product, the most likely mix quantity value can be determined. This technique is applied to experimental images to infer the quantity of CH ablator mix into the hotspot.

  4. Characterization of Small Molecule Scaffolds that Bind to the Shigella Type III Secretion System Protein IpaD

    Science.gov (United States)

    Dey, Supratim; Anbanandam, Asokan; Mumford, Ben E.; De Guzman, Roberto N.

    2017-01-01

    Many pathogens such as Shigella and other bacteria assemble the type III secretion system (T3SS) nanoinjector to inject virulence proteins into their target cells to cause infectious diseases in humans. The rise of drug resistance among pathogens that rely on the T3SS for infectivity, plus the dearth of new antibiotics require alternative strategies in developing new antibiotics. The Shigella T3SS tip protein IpaD is an attractive target for developing anti-infectives because of its essential role in virulence and its exposure on the bacterial surface. Currently, the only known small molecules that bind to IpaD are bile salts sterols. Here, we identified four new small molecule scaffolds that bind to IpaD based on the methylquinoline, pyrrolidin-aniline, hydroxyindole, and morpholinoaniline scaffolds. NMR mapping revealed potential hotspots in IpaD for binding small molecules. These scaffolds can be used as building blocks in developing small molecule inhibitors of IpaD that could lead to new anti-infectives. PMID:28750143

  5. Characterization of Small-Molecule Scaffolds That Bind to the Shigella Type III Secretion System Protein IpaD.

    Science.gov (United States)

    Dey, Supratim; Anbanandam, Asokan; Mumford, Ben E; De Guzman, Roberto N

    2017-09-21

    Many pathogens such as Shigella and other bacteria assemble the type III secretion system (T3SS) nanoinjector to inject virulence proteins into their target cells to cause infectious diseases in humans. The rise of drug resistance among pathogens that rely on the T3SS for infectivity, plus the dearth of new antibiotics require alternative strategies in developing new antibiotics. The Shigella T3SS tip protein IpaD is an attractive target for developing anti-infectives because of its essential role in virulence and its exposure on the bacterial surface. Currently, the only known small molecules that bind to IpaD are bile salt sterols. In this study we identified four new small-molecule scaffolds that bind to IpaD, based on the methylquinoline, pyrrolidine-aniline, hydroxyindole, and morpholinoaniline scaffolds. NMR mapping revealed potential hotspots in IpaD for binding small molecules. These scaffolds can be used as building blocks in developing small-molecule inhibitors of IpaD that could lead to new anti-infectives. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. A Novel Domain Cassette Identifies Plasmodium falciparum PfEMP1 Proteins Binding ICAM-1 and Is a Target of Cross-Reactive, Adhesion-Inhibitory Antibodies

    DEFF Research Database (Denmark)

    Bengtsson, Anja; Jørgensen, Louise; Rask, Thomas Salhøj

    2013-01-01

    Cerebral Plasmodium falciparum malaria is characterized by adhesion of infected erythrocytes (IEs) to the cerebral microvasculature. This has been linked to parasites expressing the structurally related group A subset of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family of IE...... to ICAM-1. The ICAM-1-binding capacity of DC4 was mapped to the C-terminal third of its Duffy-binding-like beta 3 domain. DC4 was the target of broadly cross-reactive and adhesion-inhibitory IgG Abs, and levels of DC4-specific and adhesion-inhibitory IgG increased with age among P. falciparum......-exposed children. Our study challenges earlier conclusions that group A PfEMP1 proteins are not central to ICAM-1-specific IE adhesion and support the feasibility of developing a vaccine preventing cerebral malaria by inhibiting cerebral IE sequestration. The Journal of Immunology, 2013, 190: 240-249....

  7. Schistosomiasis mansoni incidence data in Rwanda can improve prevalence assessments, by providing high-resolution hotspot and risk factors identification.

    Science.gov (United States)

    Nyandwi, E; Veldkamp, A; Amer, S; Karema, C; Umulisa, I

    2017-10-25

    Schistosomiasis mansoni constitutes a significant public health problem in Rwanda. The nationwide prevalence mapping conducted in 2007-2008 revealed that prevalence per district ranges from 0 to 69.5% among school children. In response, mass drug administration campaigns were initiated. However, a few years later some additional small-scale studies revealed the existence of areas of high transmission in districts formerly classified as low endemic suggesting the need for a more accurate methodology for identification of hotspots. This study investigated if confirmed cases of schistosomiasis recorded at health facility level can be used to, next to existing prevalence data, detect geographically more accurate hotspots of the disease and its associated risk factors. A GIS-based spatial and statistical analysis was carried out. Confirmed cases, recorded at primary health facilities level, were combined with demographic data to calculate incidence rates for each of 367 health facility service area. Empirical Bayesian smoothing was used to deal with rate instability. Incidence rates were compared with prevalence data to identify their level of agreement. Spatial autocorrelation of the incidence rates was analyzed using Moran's Index, to check if spatial clustering occurs. Finally, the spatial relationship between schistosomiasis distribution and potential risk factors was assessed using multiple regression. Incidence rates for 2007-2008 were highly correlated with prevalence values (R 2  = 0.79), indicating that in the case of Rwanda incidence data can be used as a proxy for prevalence data. We observed a focal distribution of schistosomiasis with a significant spatial autocorrelation (Moran's I > 0: 0,05-0.20 and p ≤ 0,05), indicating the occurrence of hotspots. Regarding risk factors, it was identified that the spatial pattern of schistosomiasis is significantly associated with wetland conditions and rice cultivation. In Rwanda the high density of health

  8. The Snake River Plain Volcanic Province: Insights from Project Hotspot

    Science.gov (United States)

    Shervais, J. W.; Potter, K. E.; Hanan, B. B.; Jean, M. M.; Duncan, R. A.; Champion, D. E.; Vetter, S.; Glen, J. M. G.; Christiansen, E. H.; Miggins, D. P.; Nielson, D. L.

    2017-12-01

    The Snake River Plain (SRP) Volcanic Province is the best modern example of a time-transgressive hotspot track beneath continental crust. The SRP began 17 Ma with massive eruptions of Columbia River basalt and rhyolite. After 12 Ma volcanism progressed towards Yellowstone, with early rhyolite overlain by basalts that may exceed 2 km thick. The early rhyolites are anorogenic with dry phenocryst assemblages and eruption temperatures up to 950C. Tholeiitic basalts have major and trace element compositions similar to ocean island basalts (OIB). Project Hotspot cored three deep holes in the central and western Snake River Plain: Kimama (mostly basalt), Kimberly (mostly rhyolite), and Mountain Home (lake sediments and basaslt). The Kimberly core documents rhyolite ash flows up to 700 m thick, possibly filling a caldera or sag. Chemical stratigraphy in Kimama and other basalt cores document fractional crystallization in relatively shallow magma chambers with episodic magma recharge. Age-depth relations in the Kimama core suggest accumulation rates of roughly 305 m/Ma. Surface and subsurface basalt flows show systematic variations in Sr-Nd-Pb isotopes with distance from Yellowstone interpreted to reflect changes in the proportion of plume source and the underlying heterogeneous cratonic lithosphere, which varies in age, composition, and thickness from west to east. Sr-Nd-Pb isotopes suggest <5% lithospheric input into a system dominated by OIB-like plume-derived basalts. A major flare-up of basaltic volcanism occurred 75-780 ka throughout the entire SRP, from Yellowstone in the east to Boise in the west. The youngest western SRP basalts are transitional alkali basalts that range in age from circa 900 ka to 2 ka, with trace element and isotopic compositions similar to the plume component of Hawaiian basalts. These observations suggest that ancient SCLM was replaced by plume mantle after the North America passed over the hotspot in the western SRP, which triggered renewed

  9. A novel Bayesian hierarchical model for road safety hotspot prediction.

    Science.gov (United States)

    Fawcett, Lee; Thorpe, Neil; Matthews, Joseph; Kremer, Karsten

    2017-02-01

    In this paper, we propose a Bayesian hierarchical model for predicting accident counts in future years at sites within a pool of potential road safety hotspots. The aim is to inform road safety practitioners of the location of likely future hotspots to enable a proactive, rather than reactive, approach to road safety scheme implementation. A feature of our model is the ability to rank sites according to their potential to exceed, in some future time period, a threshold accident count which may be used as a criterion for scheme implementation. Our model specification enables the classical empirical Bayes formulation - commonly used in before-and-after studies, wherein accident counts from a single before period are used to estimate counterfactual counts in the after period - to be extended to incorporate counts from multiple time periods. This allows site-specific variations in historical accident counts (e.g. locally-observed trends) to offset estimates of safety generated by a global accident prediction model (APM), which itself is used to help account for the effects of global trend and regression-to-mean (RTM). The Bayesian posterior predictive distribution is exploited to formulate predictions and to properly quantify our uncertainty in these predictions. The main contributions of our model include (i) the ability to allow accident counts from multiple time-points to inform predictions, with counts in more recent years lending more weight to predictions than counts from time-points further in the past; (ii) where appropriate, the ability to offset global estimates of trend by variations in accident counts observed locally, at a site-specific level; and (iii) the ability to account for unknown/unobserved site-specific factors which may affect accident counts. We illustrate our model with an application to accident counts at 734 potential hotspots in the German city of Halle; we also propose some simple diagnostics to validate the predictive capability of our

  10. Methodology and software to detect viral integration site hot-spots

    Science.gov (United States)

    2011-01-01

    Background Modern gene therapy methods have limited control over where a therapeutic viral vector inserts into the host genome. Vector integration can activate local gene expression, which can cause cancer if the vector inserts near an oncogene. Viral integration hot-spots or 'common insertion sites' (CIS) are scrutinized to evaluate and predict patient safety. CIS are typically defined by a minimum density of insertions (such as 2-4 within a 30-100 kb region), which unfortunately depends on the total number of observed VIS. This is problematic for comparing hot-spot distributions across data sets and patients, where the VIS numbers may vary. Results We develop two new methods for defining hot-spots that are relatively independent of data set size. Both methods operate on distributions of VIS across consecutive 1 Mb 'bins' of the genome. The first method 'z-threshold' tallies the number of VIS per bin, converts these counts to z-scores, and applies a threshold to define high density bins. The second method 'BCP' applies a Bayesian change-point model to the z-scores to define hot-spots. The novel hot-spot methods are compared with a conventional CIS method using simulated data sets and data sets from five published human studies, including the X-linked ALD (adrenoleukodystrophy), CGD (chronic granulomatous disease) and SCID-X1 (X-linked severe combined immunodeficiency) trials. The BCP analysis of the human X-linked ALD data for two patients separately (774 and 1627 VIS) and combined (2401 VIS) resulted in 5-6 hot-spots covering 0.17-0.251% of the genome and containing 5.56-7.74% of the total VIS. In comparison, the CIS analysis resulted in 12-110 hot-spots covering 0.018-0.246% of the genome and containing 5.81-22.7% of the VIS, corresponding to a greater number of hot-spots as the data set size increased. Our hot-spot methods enable one to evaluate the extent of VIS clustering, and formally compare data sets in terms of hot-spot overlap. Finally, we show that the

  11. Hotspots in clinical management of severe liver diseases

    Directory of Open Access Journals (Sweden)

    LYU Jiayu

    2017-09-01

    Full Text Available Severe liver diseases such as liver failure and acute decompensated cirrhosis have critical conditions and high mortality rates, and the prognosis of such patients is closely associated with early warning, timely dynamic assessment, and comprehensive and effective therapy. The patients require a series of effective clinical management measures for elimination of causative factors, organ support, and prevention and treatment of complications. Medical treatment-artificial liver-liver transplantation is an important modality for severe liver diseases. Granulocyte colony-stimulating factor, stem cell therapy, and bioartificial liver have a promising future, while there are still controversies over non-selective β-blocker. This article reviews the hotspots in the clinical management of severe liver diseases.

  12. Future of endemic flora of biodiversity hotspots in India.

    Directory of Open Access Journals (Sweden)

    Vishwas Sudhir Chitale

    Full Text Available India is one of the 12 mega biodiversity countries of the world, which represents 11% of world's flora in about 2.4% of global land mass. Approximately 28% of the total Indian flora and 33% of angiosperms occurring in India are endemic. Higher human population density in biodiversity hotspots in India puts undue pressure on these sensitive eco-regions. In the present study, we predict the future distribution of 637 endemic plant species from three biodiversity hotspots in India; Himalaya, Western Ghats, Indo-Burma, based on A1B scenario for year 2050 and 2080. We develop individual variable based models as well as mixed models in MaxEnt by combining ten least co-related bioclimatic variables, two disturbance variables and one physiography variable as predictor variables. The projected changes suggest that the endemic flora will be adversely impacted, even under such a moderate climate scenario. The future distribution is predicted to shift in northern and north-eastern direction in Himalaya and Indo-Burma, while in southern and south-western direction in Western Ghats, due to cooler climatic conditions in these regions. In the future distribution of endemic plants, we observe a significant shift and reduction in the distribution range compared to the present distribution. The model predicts a 23.99% range reduction and a 7.70% range expansion in future distribution by 2050, while a 41.34% range reduction and a 24.10% range expansion by 2080. Integration of disturbance and physiography variables along with bioclimatic variables in the models improved the prediction accuracy. Mixed models provide most accurate results for most of the combinations of climatic and non-climatic variables as compared to individual variable based models. We conclude that a regions with cooler climates and higher moisture availability could serve as refugia for endemic plants in future climatic conditions; b mixed models provide more accurate results, compared to single

  13. Future of endemic flora of biodiversity hotspots in India.

    Science.gov (United States)

    Chitale, Vishwas Sudhir; Behera, Mukund Dev; Roy, Partha Sarthi

    2014-01-01

    India is one of the 12 mega biodiversity countries of the world, which represents 11% of world's flora in about 2.4% of global land mass. Approximately 28% of the total Indian flora and 33% of angiosperms occurring in India are endemic. Higher human population density in biodiversity hotspots in India puts undue pressure on these sensitive eco-regions. In the present study, we predict the future distribution of 637 endemic plant species from three biodiversity hotspots in India; Himalaya, Western Ghats, Indo-Burma, based on A1B scenario for year 2050 and 2080. We develop individual variable based models as well as mixed models in MaxEnt by combining ten least co-related bioclimatic variables, two disturbance variables and one physiography variable as predictor variables. The projected changes suggest that the endemic flora will be adversely impacted, even under such a moderate climate scenario. The future distribution is predicted to shift in northern and north-eastern direction in Himalaya and Indo-Burma, while in southern and south-western direction in Western Ghats, due to cooler climatic conditions in these regions. In the future distribution of endemic plants, we observe a significant shift and reduction in the distribution range compared to the present distribution. The model predicts a 23.99% range reduction and a 7.70% range expansion in future distribution by 2050, while a 41.34% range reduction and a 24.10% range expansion by 2080. Integration of disturbance and physiography variables along with bioclimatic variables in the models improved the prediction accuracy. Mixed models provide most accurate results for most of the combinations of climatic and non-climatic variables as compared to individual variable based models. We conclude that a) regions with cooler climates and higher moisture availability could serve as refugia for endemic plants in future climatic conditions; b) mixed models provide more accurate results, compared to single variable based

  14. Revealing vilazodone's binding mechanism underlying its partial agonism to the 5-HT1A receptor in the treatment of major depressive disorder.

    Science.gov (United States)

    Zheng, Guoxun; Xue, Weiwei; Yang, Fengyuan; Zhang, Yang; Chen, Yuzong; Yao, Xiaojun; Zhu, Feng

    2017-11-01

    It has been estimated that major depressive disorder (MDD) will become the second largest global burden among all diseases by 2030. Various types of drugs, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and serotonin receptor partial agonist/reuptake inhibitors (SPARIs), have been approved and become the primary or first-line medications prescribed for MDD. SPARI was expected to demonstrate more enhanced drug efficacy and a rapid onset of action as compared to SSRI and SNRI. As one of the most famous SPARIs, vilazodone was approved by the FDA for the treatment of MDD. Because of the great clinical importance of vilazodone, its binding mechanism underlying its partial agonism to the 5-HT 1A receptor (5-HT 1A R) could provide valuable information to SPARIs' drug-like properties. However, this mechanism has not been reported to date; consequently, the rational design of new efficacious SPARI-based MDD drugs is severely hampered. To explore the molecular mechanism of vilazodone, an integrated computational strategy was adopted in this study to reveal its binding mechanism and prospective structural feature at the agonist binding site of 5-HT 1A R. As a result, 22 residues of this receptor were identified as hotspots, consistently favoring the binding of vilazodone and its analogues, and a common binding mechanism underlying their partial agonism to 5-HT 1A R was, therefore, discovered. Moreover, three main interaction features between vilazodone and 5-HT 1A R have been revealed and schematically summarized. In summary, this newly identified binding mechanism will provide valuable information for medicinal chemists working in the field of rational design of novel SPARIs for MDD treatment.

  15. HOTSPOTS DETECTION FROM TRAJECTORY DATA BASED ON SPATIOTEMPORAL DATA FIELD CLUSTERING

    Directory of Open Access Journals (Sweden)

    K. Qin

    2017-09-01

    Full Text Available City hotspots refer to the areas where residents visit frequently, and large traffic flow exist, which reflect the people travel patterns and distribution of urban function area. Taxi trajectory data contain abundant information about urban functions and citizen activities, and extracting interesting city hotspots from them can be of importance in urban planning, traffic command, public travel services etc. To detect city hotspots and discover a variety of changing patterns among them, we introduce a data field-based cluster analysis technique to the pick-up and drop-off points of taxi trajectory data and improve the method by introducing the time weight, which has been normalized to estimate the potential value in data field. Thus, in the light of the new potential function in data field, short distance and short time difference play a powerful role. So the region full of trajectory points, which is regarded as hotspots area, has a higher potential value, while the region with thin trajectory points has a lower potential value. The taxi trajectory data of Wuhan city in China on May 1, 6 and 9, 2015, are taken as the experimental data. From the result, we find the sustaining hotspots area and inconstant hotspots area in Wuhan city based on the spatiotemporal data field method. Further study will focus on optimizing parameter and the interaction among hotspots area.

  16. An Investigation on Hot-Spot Temperature Calculation Methods of Power Transformers

    OpenAIRE

    Ahmet Y. Arabul; Ibrahim Senol; Fatma Keskin Arabul; Mustafa G. Aydeniz; Yasemin Oner; Gokhan Kalkan

    2016-01-01

    In the standards of IEC 60076-2 and IEC 60076-7, three different hot-spot temperature estimation methods are suggested. In this study, the algorithms which used in hot-spot temperature calculations are analyzed by comparing the algorithms with the results of an experimental set-up made by a Transformer Monitoring System (TMS) in use. In tested system, TMS uses only top oil temperature and load ratio for hot-spot temperature calculation. And also, it uses some constants from standards which ar...

  17. Natural landscape features, human-related attractants, and conflict hotspots: A spatial analysis of human-grizzly bear conflicts

    Science.gov (United States)

    Wilson, S.M.; Madel, M.J.; Mattson, D.J.; Graham, J.M.; Burchfield, J.A.; Belsky, J.M.

    2005-01-01

    There is a long history of conflict in the western United States between humans and grizzly bears (Ursus arctos) involving agricultural attractants. However, little is known about the spatial dimensions of this conflict and the relative importance of different attractants. This study was undertaken to better understand the spatial and functional components of conflict between humans and grizzly bears on privately owned agricultural lands in Montana. Our investigations focused on spatial associations of rivers and creeks, livestock pastures, boneyards (livestock carcass dump sites), beehives, and grizzly bear habitat with reported human-grizzly bear conflicts during 1986-2001. We based our analysis on a survey of 61 of 64 livestock producers in our study in the Rocky Mountain East Front, Montana. With the assistance of livestock and honey producers, we mapped the locations of cattle and sheep pastures, boneyards, and beehives. We used density surface mapping to identify seasonal clusters of conflicts that we term conflict hotspots. Hotspots accounted for 75% of all conflicts and encompassed approximately 8% of the study area. We also differentiated chronic (4 or more years of conflicts) from non-chronic hotspots (fewer than 4 years of conflict). The 10 chronic hotpots accounted for 58% of all conflicts. Based on Monte Carlo simulations, we found that conflict locations were most strongly associated with rivers and creeks followed by sheep lambing areas and fall sheep pastures. Conflicts also were associated with cattle calving areas, spring cow-calf pastures, summer and fall cattle pastures, and boneyards. The Monte Carlo simulations indicated associations between conflict locations and unprotected beehives at specific analysis scales. Protected (fenced) beehives were less likely to experience conflicts than unprotected beehives. Conflicts occurred at a greater rate in riparian and wetland vegetation than would be expected. The majority of conflicts occurred in a

  18. Pictorial binding: endeavor to classify

    Directory of Open Access Journals (Sweden)

    Zinchenko S.

    2015-01-01

    Full Text Available The article is devoted to the classification of bindings of the 1-19th centuries with a unique and untypical book binding decoration technique (encaustic, tempera and oil paintings. Analysis of design features, materials and techniques of art decoration made it possible to identify them as a separate type - pictorial bindings and divide them into four groups. The first group consists of Coptic bindings, decorated with icon-painting images in encaustic technique. The second group is made up of leather Western bindings of the 13-14th centuries, which have the decoration and technique of ornamentation close to iconography. The third group involves parchment bindings, ornamentation technique of which is closer to the miniature. The last group comprises bindings of East Slavic origin of the 15-19th centuries, decorated with icon-painting pictures made in the technique of tempera or oil painting. The proposed classification requires further basic research as several specific kinds of bindings have not yet been investigated

  19. Predicting bycatch hotspots for endangered leatherback turtles on longlines in the Pacific Ocean.

    Science.gov (United States)

    Roe, John H; Morreale, Stephen J; Paladino, Frank V; Shillinger, George L; Benson, Scott R; Eckert, Scott A; Bailey, Helen; Tomillo, Pilar Santidrián; Bograd, Steven J; Eguchi, Tomoharu; Dutton, Peter H; Seminoff, Jeffrey A; Block, Barbara A; Spotila, James R

    2014-02-22

    Fisheries bycatch is a critical source of mortality for rapidly declining populations of leatherback turtles, Dermochelys coriacea. We integrated use-intensity distributions for 135 satellite-tracked adult turtles with longline fishing effort to estimate predicted bycatch risk over space and time in the Pacific Ocean. Areas of predicted bycatch risk did not overlap for eastern and western Pacific nesting populations, warranting their consideration as distinct management units with respect to fisheries bycatch. For western Pacific nesting populations, we identified several areas of high risk in the north and central Pacific, but greatest risk was adjacent to primary nesting beaches in tropical seas of Indo-Pacific islands, largely confined to several exclusive economic zones under the jurisdiction of national authorities. For eastern Pacific nesting populations, we identified moderate risk associated with migrations to nesting beaches, but the greatest risk was in the South Pacific Gyre, a broad pelagic zone outside national waters where management is currently lacking and may prove difficult to implement. Efforts should focus on these predicted hotspots to develop more targeted management approaches to alleviate leatherback bycatch.