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  • Articles  (134)
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  • Articles  (134)
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  • 1
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    Quantifying the contribution of recessive coding variation to developmental disorders (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018
    Description: 〈p〉We estimated the genome-wide contribution of recessive coding variation in 6040 families from the Deciphering Developmental Disorders study. The proportion of cases attributable to recessive coding variants was 3.6% in patients of European ancestry, compared with 50% explained by de novo coding mutations. It was higher (31%) in patients with Pakistani ancestry, owing to elevated autozygosity. Half of this recessive burden is attributable to known genes. We identified two genes not previously associated with recessive developmental disorders, 〈i〉KDM5B〈/i〉 and 〈i〉EIF3F〈/i〉, and functionally validated them with mouse and cellular models. Our results suggest that recessive coding variants account for a small fraction of currently undiagnosed nonconsanguineous individuals, and that the role of noncoding variants, incomplete penetrance, and polygenic mechanisms need further exploration.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Hierarchical interlocked orthogonal faulting in the 2019 Ridgecrest earthquake sequence (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉 A nearly 20-year hiatus in major seismic activity in southern California ended on 4 July 2019 with a sequence of intersecting earthquakes near the city of Ridgecrest, California. This sequence included a foreshock with a moment magnitude (〈i〉M〈/i〉〈sub〉w〈/sub〉) of 6.4 followed by a 〈i〉M〈/i〉〈sub〉w〈/sub〉 7.1 mainshock nearly 34 hours later. Geodetic, seismic, and seismicity data provided an integrative view of this sequence, which ruptured an unmapped multiscale network of interlaced orthogonal faults. This complex fault geometry persists over the entire seismogenic depth range. The rupture of the mainshock terminated only a few kilometers from the major regional Garlock fault, triggering shallow creep and a substantial earthquake swarm. The repeated occurrence of multifault ruptures, as revealed by modern instrumentation and analysis techniques, poses a formidable challenge in quantifying regional seismic hazards.〈/p〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    A Bayesian Monte-Carlo Inversion of Spatial Auto-Correlation (SPAC) for Near-Surface Vs Structure Applied to both Broadband and Geophone Data (2019)
    Oxford University Press
    Details
    Publication Date: 2019
    Description: 〈span〉〈div〉Summary〈/div〉We propose a new Bayesian method to reveal the 〈span〉Vs〈/span〉 structure of the near surface of the earth using spatial autocorrelation (SPAC) functions and apply this new method to synthetic, broadband, and geophone datasets. The principle of SPAC is introduced, and an implementation of the Bayesian Monte Carlo inversion (BMCI) for modeling SPAC coherency functions is described. To demonstrate its effectiveness, BMCI is applied to synthetic tests, data from 14 SPAC array sites in the Salt Lake Valley (SLV), Utah, and two arrays (one broadband and one geophone) located in south central Utah. The 〈span〉Vs〈/span〉 models derived from previous SPAC analysis of the 14 SLV sites differ by 10 per cent at most from those determined by BMCI and lie within uncertainties determined for the BMCI models. These agreements demonstrate the effectiveness of the BMCI method. The synthetic tests and applications to the SLV SPAC data show BMCI has great potential to resolve 〈span〉Vs〈/span〉 structure down to at least 400 m. To achieve resolution for deeper 〈span〉Vs〈/span〉 structure, longer duration deployments, wider array apertures, and additional seismometers or geophones can be employed. Additionally, when the target frequencies are greater than 0.1 Hz, there is no apparent disadvantage in using geophone data for BMCI compared to broadband data. Most significantly, BMCI places a quantifiable constraint on the uncertainties of the 〈span〉Vs〈/span〉 models as well as 〈span〉Vs30〈/span〉.〈/span〉
    Print ISSN: 2051-1965
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 4
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    Willingness to use couples HIV testing and discussion of sexual agreements among heterosexuals (2015)
    SpringerOpen
    Details
    Publication Date: 2015-04-14
    Description: Couples HIV Testing and Counseling (CHTC) has been used as an HIV prevention strategy in Africa for over 20 years where the HIV epidemic is largely concentrated among sexually active heterosexuals. In recent years, CHTC has been adapted for men who have sex with men (MSM) in the US. A central element of the CHTC intervention as adapted for male couples in the US is the discussion of sexual agreements by the dyad during the CHTC session. Given the success of CHTC for heterosexual couples in Africa, it seems appropriate that CHTC could also be provided to heterosexual couples in the US. However, little is known about heterosexual’s willingness to utilize CHTC services including discussion of sexual agreements. This small, preliminary qualitative study sheds new light on the potential for CHTC adoption among heterosexuals in the US. Four focus groups were conducted with heterosexual men and women attending a publicly-funded STI clinic, to explore the potential feasibility and acceptability of CHTC with heterosexuals. The results are similar to those seen for MSM: high levels of willingness to use CHTC, perceptions of the advantages of using CHTC, and willingness to discuss sexual agreements; all necessary conditions for the successful roll-out of CHTC. Further work is now needed with larger samples of high-risk heterosexuals to more completely understand the typologies of sexual agreements and the common language used for sexual agreements in heterosexual relationships. These early data show great promise that CHTC can achieve the same levels of willingness, fit, and acceptability among heterosexual couples as currently experienced by male couples in the US.
    Electronic ISSN: 2193-1801
    Topics: Natural Sciences in General
    Published by SpringerOpen
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  • 5
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    Acceptability and willingness among men who have sex with men (MSM) to use a tablet-based HIV risk assessment in a clinical setting (2014)
    SpringerOpen
    Details
    Publication Date: 2014-12-03
    Description: We developed an iPad-based application to administer an HIV risk assessment tool in a clinical setting. We conducted focus group discussions (FGDs) with gay, bisexual and other men who have sex with men (MSM) to assess their opinions about using such a device to share risk behavior information in a clinical setting. Participants were asked about their current assessment of their risk or any risk reduction strategies that they discussed with their healthcare providers. Participants were then asked to provide feedback about the iPad-based risk assessment, their opinions about using it in a clinic setting, and suggestions on how the assessment could be improved. FGD participants were generally receptive to the idea of using an iPad-based risk assessment during healthcare visits. Based on the results of the FGDs, an iPad-based risk assessment is a promising method for identifying those patients at highest risk for HIV transmission.
    Electronic ISSN: 2193-1801
    Topics: Natural Sciences in General
    Published by SpringerOpen
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  • 6
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    The crustal structure of Ellesmere Island, Arctic Canada--teleseismic mapping across a remote intraplate orogenic belt (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-30
    Description: Ellesmere Island in Arctic Canada displays a complex geological evolution. The region was affected by two distinct orogenies, the Palaeozoic Ellesmerian orogeny (the Caledonian equivalent in Arctic Canada and Northern Greenland) and the Palaeogene Eurekan orogeny, related to the opening of Baffin Bay and the consequent convergence of the Greenland plate. The details of this complex evolution and the present-day deep structure are poorly constrained in this remote area and deep geophysical data are sparse. Receiver function analysis of seven temporary broad-band seismometers of the Ellesmere Island Lithosphere Experiment complemented by two permanent stations provides important data on the crustal velocity structure of Ellesmere Island. The crustal expression of the northernmost tectonic block of Ellesmere Island (~82°–83°N), Pearya, which was accreted during the Ellesmerian orogeny, is similar to that at the southernmost part, which is part of the Precambrian Laurentian (North America-Greenland) craton. Both segments have thick crystalline crust (~35–36 km) and comparable velocity–depth profiles. In contrast, crustal thickness in central Ellesmere Island decreases from ~24–30 km in the Eurekan fold and thrust belt (~79.7°–80.6°N) to ~16–20 km in the Hazen Stable Block (HSB; ~80.6°–81.4°N) and is covered by a thick succession of metasediments. A deep crustal root (~48 km) at ~79.6°N is interpreted as cratonic crust flexed beneath the Eurekan fold and thrust belt. The Carboniferous to Palaeogene sedimentary succession of the Sverdrup Basin is inferred to be up to 1–4 km thick, comparable to geologically-based estimates, near the western margin of the HSB.
    Keywords: Geodynamics and Tectonics
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 7
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    Characterization of crustal structure by comparing reflectivity patterns of wide-angle and near vertical seismic data from the Parnaíba Basin, Brazil (2019)
    Oxford University Press
    Details
    Publication Date: 2019
    Description: 〈span〉〈div〉SUMMARY〈/div〉Recently an ambitious experiment combining deep seismic surveys from near-vertical and wide-angle acquisition methods was carried out in Brazil. The seismic lines are essentially coincident and crossed the Parnaíba Basin from west to east near latitude 5°S. Here, the wide-angle reflection and refraction (WARR) and deep seismic reflection (DSR) results, which were previously interpreted independently, are compared by directly correlating WARR interfaces converted to TWTT with the major reflective horizons identified in the zero-offset image and by considering coincident reflectivity patterns displayed in both data sets. This integrated WARR and DSR analysis allowed a spatial association of the apparently acoustically featureless crust imaged in the DSR profile to the high reflectivity observed in the WARR data. Numerical tests and elastic modelling show that variations of the elastic properties of the crust, particularly as they are characterized by low 〈span〉Vp〈/span〉 and 〈span〉Vs〈/span〉 contrasts with a possible increase of the 〈span〉Vp〈/span〉/〈span〉Vs〈/span〉 ratio, can only weakly explain the observed reflectivity patterns but that fine-scale lithological heterogeneity within the crust is capable of replicating the observed contrasting seismic responses. The segment of the Parnaíba Basin crust that is characterized by fine-scale lithological heterogeneity lies directly above a mafic crustal underplate defined by the WARR model and was named as the Grajaú domain on the basis of WARR-derived velocity model. The applied methodologies allow added value to be taken from the independent seismic data sets and provide new information about crustal structure that may have important implications for overlying intracontinental basin evolution.〈/span〉
    Print ISSN: 2051-1965
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 8
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    Adaptation of the African couples HIV testing and counseling model for men who have sex with men in the United States: an application of the ADAPT-ITT framework (2014)
    SpringerOpen
    Details
    Publication Date: 2014-05-17
    Description: To respond to the need for new HIV prevention services for men who have sex with men (MSM) in the United States, and to respond to new data on the key role of main partnerships in US MSM epidemics, we sought to develop a new service for joint HIV testing of male couples. We used the ADAPT-ITT framework to guide our work. From May 2009 to July 2013, a multiphase process was undertaken to identify an appropriate service as the basis for adaptation, collect data to inform the adaptation, adapt the testing service, develop training materials, test the adapted service, and scale up and evaluate the initial version of the service. We chose to base our adaptation on an African couples HIV testing service that was developed in the 1980s and has been widely disseminated in low- and middle-income countries. Our adaptation was informed by qualitative data collections from MSM and HIV counselors, multiple online surveys of MSM, information gathering from key stakeholders, and theater testing of the adapted service with MSM and HIV counselors. Results of initial testing indicate that the adapted service is highly acceptable to MSM and to HIV counselors, that there are no evident harms (e.g., intimate partner violence, relationship dissolution) associated with the service, and that the service identifies a substantial number of HIV serodiscordant male couples. The story of the development and scale-up of the adapted service illustrates how multiple public and foundation funding sources can collaborate to bring a prevention adaptation from concept to public health application, touching on research, program evaluation, implementation science, and public health program delivery. The result of this process is an adapted couples HIV testing approach, with training materials and handoff from academic partners to public health for assessment of effectiveness and consideration of the potential benefits of implementation; further work is needed to optimally adapt the African couples testing service for use with male-female couples in the United States.
    Electronic ISSN: 2193-1801
    Topics: Natural Sciences in General
    Published by SpringerOpen
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  • 9
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    A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-06-01
    Description: The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mural, Richard J -- Adams, Mark D -- Myers, Eugene W -- Smith, Hamilton O -- Miklos, George L Gabor -- Wides, Ron -- Halpern, Aaron -- Li, Peter W -- Sutton, Granger G -- Nadeau, Joe -- Salzberg, Steven L -- Holt, Robert A -- Kodira, Chinnappa D -- Lu, Fu -- Chen, Lin -- Deng, Zuoming -- Evangelista, Carlos C -- Gan, Weiniu -- Heiman, Thomas J -- Li, Jiayin -- Li, Zhenya -- Merkulov, Gennady V -- Milshina, Natalia V -- Naik, Ashwinikumar K -- Qi, Rong -- Shue, Bixiong Chris -- Wang, Aihui -- Wang, Jian -- Wang, Xin -- Yan, Xianghe -- Ye, Jane -- Yooseph, Shibu -- Zhao, Qi -- Zheng, Liansheng -- Zhu, Shiaoping C -- Biddick, Kendra -- Bolanos, Randall -- Delcher, Arthur L -- Dew, Ian M -- Fasulo, Daniel -- Flanigan, Michael J -- Huson, Daniel H -- Kravitz, Saul A -- Miller, Jason R -- Mobarry, Clark M -- Reinert, Knut -- Remington, Karin A -- Zhang, Qing -- Zheng, Xiangqun H -- Nusskern, Deborah R -- Lai, Zhongwu -- Lei, Yiding -- Zhong, Wenyan -- Yao, Alison -- Guan, Ping -- Ji, Rui-Ru -- Gu, Zhiping -- Wang, Zhen-Yuan -- Zhong, Fei -- Xiao, Chunlin -- Chiang, Chia-Chien -- Yandell, Mark -- Wortman, Jennifer R -- Amanatides, Peter G -- Hladun, Suzanne L -- Pratts, Eric C -- Johnson, Jeffery E -- Dodson, Kristina L -- Woodford, Kerry J -- Evans, Cheryl A -- Gropman, Barry -- Rusch, Douglas B -- Venter, Eli -- Wang, Mei -- Smith, Thomas J -- Houck, Jarrett T -- Tompkins, Donald E -- Haynes, Charles -- Jacob, Debbie -- Chin, Soo H -- Allen, David R -- Dahlke, Carl E -- Sanders, Robert -- Li, Kelvin -- Liu, Xiangjun -- Levitsky, Alexander A -- Majoros, William H -- Chen, Quan -- Xia, Ashley C -- Lopez, John R -- Donnelly, Michael T -- Newman, Matthew H -- Glodek, Anna -- Kraft, Cheryl L -- Nodell, Marc -- Ali, Feroze -- An, Hui-Jin -- Baldwin-Pitts, Danita -- Beeson, Karen Y -- Cai, Shuang -- Carnes, Mark -- Carver, Amy -- Caulk, Parris M -- Center, Angela -- Chen, Yen-Hui -- Cheng, Ming-Lai -- Coyne, My D -- Crowder, Michelle -- Danaher, Steven -- Davenport, Lionel B -- Desilets, Raymond -- Dietz, Susanne M -- Doup, Lisa -- Dullaghan, Patrick -- Ferriera, Steven -- Fosler, Carl R -- Gire, Harold C -- Gluecksmann, Andres -- Gocayne, Jeannine D -- Gray, Jonathan -- Hart, Brit -- Haynes, Jason -- Hoover, Jeffery -- Howland, Tim -- Ibegwam, Chinyere -- Jalali, Mena -- Johns, David -- Kline, Leslie -- Ma, Daniel S -- MacCawley, Steven -- Magoon, Anand -- Mann, Felecia -- May, David -- McIntosh, Tina C -- Mehta, Somil -- Moy, Linda -- Moy, Mee C -- Murphy, Brian J -- Murphy, Sean D -- Nelson, Keith A -- Nuri, Zubeda -- Parker, Kimberly A -- Prudhomme, Alexandre C -- Puri, Vinita N -- Qureshi, Hina -- Raley, John C -- Reardon, Matthew S -- Regier, Megan A -- Rogers, Yu-Hui C -- Romblad, Deanna L -- Schutz, Jakob -- Scott, John L -- Scott, Richard -- Sitter, Cynthia D -- Smallwood, Michella -- Sprague, Arlan C -- Stewart, Erin -- Strong, Renee V -- Suh, Ellen -- Sylvester, Karena -- Thomas, Reginald -- Tint, Ni Ni -- Tsonis, Christopher -- Wang, Gary -- Wang, George -- Williams, Monica S -- Williams, Sherita M -- Windsor, Sandra M -- Wolfe, Keriellen -- Wu, Mitchell M -- Zaveri, Jayshree -- Chaturvedi, Kabir -- Gabrielian, Andrei E -- Ke, Zhaoxi -- Sun, Jingtao -- Subramanian, Gangadharan -- Venter, J Craig -- Pfannkoch, Cynthia M -- Barnstead, Mary -- Stephenson, Lisa D -- New York, N.Y. -- Science. 2002 May 31;296(5573):1661-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Celera Genomics, 45 West Gude Drive, Rockville, MD 20850, USA. richard.mural@celera.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12040188" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Composition ; Chromosomes/*genetics ; Chromosomes, Human/genetics ; Computational Biology ; Conserved Sequence ; Databases, Nucleic Acid ; Evolution, Molecular ; Genes ; Genetic Markers ; *Genome ; *Genome, Human ; Genomics ; Humans ; Mice ; Mice, Inbred A/genetics ; Mice, Inbred DBA/genetics ; Mice, Inbred Strains/*genetics ; Molecular Sequence Data ; Physical Chromosome Mapping ; Proteins/chemistry/genetics ; Sequence Alignment ; *Sequence Analysis, DNA ; Species Specificity ; *Synteny
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 10
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    Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors (2018)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2018-08-10
    Description: Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines the identities of malignant cells and the diversity of tumor tissue. We studied 72,501 single-cell transcriptomes of human renal tumors and normal tissue from fetal, pediatric, and adult kidneys. We matched childhood Wilms tumor with specific fetal cell types, thus providing evidence for the hypothesis that Wilms tumor cells are aberrant fetal cells. In adult renal cell carcinoma, we identified a canonical cancer transcriptome that matched a little-known subtype of proximal convoluted tubular cell. Analyses of the tumor composition defined cancer-associated normal cells and delineated a complex vascular endothelial growth factor (VEGF) signaling circuit. Our findings reveal the precise cellular identities and compositions of human kidney tumors.
    Keywords: Development, Medicine, Diseases
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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