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Blaess, Sandra ; Bodea, Gabriela O. ; Kabanova, Anna ; Chanet, Soline ; Mugniery, Emilie ; Derouiche, Amin ; Stephen, Daniel ; Joyner, Alexandra L.
Background: The ventral midbrain contains a diverse array of neurons, including dopaminergic neurons of the ventral tegmental area (VTA) and substantia nigra (SN) and neurons of the red nucleus (RN). Dopaminergic and RN neurons have been shown to arise from ventral mesencephalic precursors that express Sonic Hedgehog (Shh). However, Shh expression, which is initially confined to the mesencephalic ventral midline, expands laterally and is then downregulated in the ventral midline. In contrast, expression of the Hedgehog target gene Gli1 initiates in the ventral midline prior to Shh expression, but after the onset of Shh expression it is expressed in precursors lateral to Shh-positive cells. Given these dynamic gene expression patterns, Shh and Gli1 expression could delineate different progenitor populations at distinct embryonic time points. Results: We employed genetic inducible fate mapping (GIFM) to investigate whether precursors that express Shh (Shh-GIFM) or transduce Shh signaling (Gli1-GIFM) at different time points give rise to different ventral midbrain cell types. We find that precursors restricted to the ventral midline are labeled at embryonic day (E)7.5 with Gli1-GIFM, and with Shh-GIFM at E8.5. These precursors give rise to all subtypes of midbrain dopaminergic neurons and the anterior RN. A broader domain of progenitors that includes the ventral midline is marked with Gli1-GIFM at E8.5 and with Shh-GIFM at E9.5; these fate-mapped cells also contribute to all midbrain dopaminergic subtypes and to the entire RN. In contrast, a lateral progenitor domain that is labeled with Gli1-GIFM at E9.5 and with Shh-GIFM at E11.5 has a markedly reduced potential to give rise to the RN and to SN dopaminergic neurons, and preferentially gives rise to the ventral-medial VTA. In addition, cells derived from Shh- and Gli1-expressing progenitors located outside of the ventral midline give rise to astrocytes. Conclusions: We define a ventral midbrain precursor map based on the timing of Gli1 and Shh expression, and suggest that the diversity of midbrain dopaminergic neurons is at least partially determined during their precursor stage when their medial-lateral position, differential gene expression and the time when they leave the ventricular zone influence their fate decisions.
Blagosklonny, Mikhail V. ; Campisi, Judy ; Sinclair, David A. ; Bartke, Andrzej ; Blasco, Maria A. ; Bonner, William M. ; Bohr, Vilhelm A. ; Brosh, Robert M. ; Brunet, Anne ; DePinho, Ronald A. ; Donehower, Lawrence A. ; Finch, Caleb E. ; Finkel, Toren ; Gorospe, Myriam ; Gudkov, Andrei V. ; Hall, Michael N. ; Hekimi, Siegfried ; Helfand, Stephen L. ; Karlseder, Jan ; Kenyon, Cynthia ; Kroemer, Guido ; Longo, Valter ; Nussenzweig, Andre ; Osiewacz, Heinz D. ; Peeper, Daniel S. ; Rando, Thomas A. ; Rudolph, K. Lenhard ; Sassone-Corsi, Paolo ; Serrano, Manuel ; Sharpless, Norman E. ; Skulachev, Vladimir P. ; Tilly, Jonathan L. ; Tower, John ; Verdin, Eric ; Vijg, Jan
The editorial board of Aging reviews research papers published in 2009,which they believe have or will have a significant impact on aging research.Among many others, the topics include genes that accelerate aging or incontrast promote longevity in model organisms, DNA damage responsesand telomeres, molecular mechanisms of life span extension by calorierestriction and pharmacologic interventions into aging. The emergingmessage in 2009 is that aging is not random but determined by agenetically-regulated longevity network and can be decelerated bothgenetically and pharmacologically.
Himmelstein, Daniel S. ; Rodriguez Romero, Ariel ; McLaughlin, Stephen Reid ; Tzovaras, Bastian Greshake ; Greene, Casey S.
The website Sci-Hub provides access to scholarly literature via full text PDF downloads. The site enables users to access articles that would otherwise be paywalled. Since its creation in 2011, SciHub has grown rapidly in popularity. However, until now, the extent of Sci-Hub’s coverage was unclear. As of March 2017, we find that Sci-Hub’s database contains 68.9% of all 81.6 million scholarly articles, which rises to 85.2% for those published in toll access journals. Coverage varies by discipline, with 92.8% coverage of articles in chemistry journals compared to 76.3% for computer science. Coverage also varies by publisher, with the coverage of the largest publisher, Elsevier, at 97.3%. Our interactive browser at greenelab.github.io/scihub allows users to explore these findings in more detail. We find Sci-Hub preferentially covers popular, paywalled content, containing 96.2% of citations to toll access journals since 2015. For recently requested articles by Unpaywall users, oaDOI provided access to 48.8% whereas Sci-Hub contained 81.5%. Together, oaDOI and Sci-Hub covered 94.1%, demonstrating that gaps in Sci-Hub’s coverage, especially for open access articles, can be filled using licit services. For the first time, nearly all scholarly literature is available gratis to anyone with an Internet connection. Sci-Hub’s scope suggests the subscription publishing model is becoming unsustainable.
Himmelstein, Daniel S. ; Rodriguez Romero, Ariel ; Levernier, Jacob ; Munro, Thomas Anthony ; McLaughlin, Stephen Reid ; Tzovaras, Bastian Greshake ; Greene, Casey S.
The website Sci-Hub enables users to download PDF versions of scholarly articles, including many articles that are paywalled at their journal’s site. Sci-Hub has grown rapidly since its creation in 2011, but the extent of its coverage was unclear. Here we report that, as of March 2017, Sci-Hub’s database contains 68.9% of the 81.6 million scholarly articles registered with Crossref and 85.2% of articles published in toll access journals. We find that coverage varies by discipline and publisher and that Sci-Hub preferentially covers popular, paywalled content. For toll access articles, green open access via licit services is quite limited, while Sci-Hub provides greater coverage than a major research university. Our interactive browser at https://greenelab.github.io/scihub allows users to explore these findings in more detail. For the first time, nearly all scholarly literature is available gratis to anyone with an Internet connection, suggesting the toll access business model will become unsustainable.
Himmelstein, Daniel S. ; Rodriguez Romero, Ariel ; Levernier, Jacob ; Munro, Thomas Anthony ; McLaughlin, Stephen Reid ; Tzovaras, Bastian Greshake ; Greene, Casey S.
The website Sci-Hub enables users to download PDF versions of scholarly articles, including many articles that are paywalled at their journal’s site. Sci-Hub has grown rapidly since its creation in 2011, but the extent of its coverage has been unclear. Here we report that, as of March 2017, Sci-Hub’s database contains 68.9% of the 81.6 million scholarly articles registered with Crossref and 85.1% of articles published in toll access journals. We find that coverage varies by discipline and publisher, and that Sci-Hub preferentially covers popular, paywalled content. For toll access articles, we find that Sci-Hub provides greater coverage than the University of Pennsylvania, a major research university in the United States. Green open access to toll access articles via licit services, on the other hand, remains quite limited. Our interactive browser at https://greenelab.github.io/scihub allows users to explore these findings in more detail. For the first time, nearly all scholarly literature is available gratis to anyone with an Internet connection, suggesting the toll access business model may become unsustainable.
Himmelstein, Daniel S. ; Rodriguez Romero, Ariel ; McLaughlin, Stephen Reid ; Tzovaras, Bastian Greshake ; Greene, Casey S.
The website Sci-Hub provides access to scholarly literature via full text PDF downloads. The site enables users to access articles that would otherwise be paywalled. Since its creation in 2011, Sci-Hub has grown rapidly in popularity. However, until now, the extent of Sci-Hub's coverage was unclear. As of March 2017, we find that Sci-Hub's database contains 68.9% of all 81.6 million scholarly articles, which rises to 85.2% for those published in closed access journals. Furthermore, Sci-Hub contains 77.0% of the 5.2 million articles published by inactive journals. Coverage varies by discipline, with 92.8% coverage of articles in chemistry journals compared to 76.3% for computer science. Coverage also varies by publisher, with the coverage of the largest publisher, Elsevier, at 97.3%. Our interactive browser at https://greenelab.github.io/scihub allows users to explore these findings in more detail. Finally, we estimate that over a six-month period in 2015–2016, Sci-Hub provided access for 99.3% of valid incoming requests. Hence, the scope of this resource suggests the subscription publishing model is becoming unsustainable. For the first time, the overwhelming majority of scholarly literature is available gratis to anyone with an Internet connection.
Tozer, Mark G. ; Turner, Ken ; Keith, David A. ; Tindall, Daniel ; Pennay, Christopher ; Simpson, Christopher C. ; MacKenzie, Berin ; Beukers, P. ; Cox, Stephen
Native vegetation of the NSW south coast, escarpment and southeast tablelands was classified into 191 floristic assemblages at a level of detail appropriate for the discrimination of Threatened Ecological Communities and other vegetation units referred to in government legislation. Assemblages were derived by a numerical analysis of 10832 field sample quadrats including 8523 compiled from 63 previous vegetation surveys. Past bias in the distribution of field data towards land under public tenure was corrected by extensive surveys carried out on private land. The classification revises and integrates the units described in recent vegetation studies of Eden, Cumberland Plain and Sydney-south coast into a single, consistent classification. Relationships between floristic assemblages and climate, terrain, substrate and vegetation structure were used to map the distribution of communities prior to clearing at 1:100 000 scale. The extent of clearing was mapped using interpretations of remote imagery (1991–2001) from previous work, standardised and merged into a single coverage and supplemented with additional work. Profiles for each assemblage, which we term ‘communities’ or ‘map units’, describe their species composition, vegetation structure, environmental habitat, the extent of clearing and conservation status. Lists of diagnostic species were defined using a statistical fidelity measure and a procedure for using these for community identification is described. Approximately 66% of the study area retains a cover of native vegetation, primarily in areas with low fertility soils and dissected topography. Communities subject to over-clearing (>70%) are concentrated in a few large areas characterised by clay/loam soils and flat to undulating terrain. These include the Sydney metropolis, Wingecarribee Plateau, Illawarra Plain, Shoalhaven floodplain, Araluen Valley and Bega Valley, and various smaller river valleys. Forty-one percent of remaining native vegetation is protected within conservation reserves while 31% occurs on private land, 20% in State Forests and 8% on other Crown lands. Forty-five Threatened Ecological Communities (TECs) were recorded in the study area. The majority of TECs are represented by a single map unit, although in some cases a TEC is included within a broader map unit. Twelve TECs are represented by combinations of two or more map units.
Krimphove, Marieke Johanna ; Reese, Stephen W. ; Chen, Xi ; Marchese, Maya ; Pucheril, Daniel ; Cone, Eugene ; Chou, Wesley ; Tully, Karl Heinrich ; Kibel, Adam S. ; Urman, Richard D. ; Chang, Steven L. ; Kluth, Luis A. ; Dasgupta, Prokar ; Trinh, Quoc-Dien
Purpose: Does surgical approach (minimally invasive vs. open) and type (radical vs. partial nephrectomy) affects opioid use and workplace absenteeism.
Materials and Methods: Retrospective multivariable regression analysis of 2,646 opioid-naïve patients between 18 and 64 undergoing radical or partial nephrectomy via either a minimally invasive vs. open approach for kidney cancer in the United States between 2012 and 2017 drawn from the IBM Watson Health Database was performed. Outcomes included: (1) opioid use in opioid-naïve patients as measured by opioid prescriptions in the post-operative setting at early, intermediate and prolonged time periods and (2) workplace absenteeism after surgery.
Results: Patients undergoing minimally invasive surgery had a lower odds of opioid use in the early and intermediate post-operative periods (early: odds ratio [OR], 0.77; 95% confidence interval [CI], 0.62–0.97; p=0.02, intermediate: OR, 0.60; 95% CI, 0.48–0.75; p<0.01), but not in the prolonged setting (prolonged: OR, 1.00; 95% CI, 0.75–1.34; p=0.98) and had earlier return to work (minimally invasive vs. open: −10.53 days; 95% CI, −17.79 to −3.26; p<0.01). Controlling for approach, patient undergoing partial nephrectomy had lower rates of opioid use across all time periods examined and returned to work earlier than patients undergoing radical nephrectomy (partial vs. radical: −14.41 days; 95% CI, −21.22 to −7.60; p<0.01).
Conclusions: Patients undergoing various forms of surgery for kidney cancer had lower rates of peri-operative opioid use, fewer days of workplace absenteeism, but no difference in long-term rates of opioid use in patients undergoing minimally invasive as compared to open surgery.
Unique features of a global human ectoparasite identified through sequencing of the bed bug genome
(2016)
Benoit, Joshua B. ; Adelman, Zach N. ; Reinhardt, Klaus ; Dolan, Amanda ; Poelchau, Monica ; Jennings, Emily C. ; Szuter, Elise M. ; Hagan, Richard W. ; Gujar, Hemant ; Shukla, Jayendra Nath ; Zhu, Fang ; Mohan, Muthugounder ; Nelson, David R. ; Rosendale, Andrew J. ; Derst, Christian ; Resnik, Valentina ; Wernig, Sebastian ; Menegazzi, Pamela ; Wegener, Christian ; Peschel, Nicolai ; Hendershot, Jacob M. ; Blenau, Wolfgang ; Predel, Reinhard ; Johnston, Paul R. ; Ioannidis, Panagiotis ; Waterhouse, Robert M. ; Nauen, Ralf ; Schorn, Corinna ; Ott, Mark-Christoph ; Maiwald, Frank ; Johnston, J. Spencer ; Gondhalekar, Ameya D. ; Scharf, Michael E. ; Peterson, Brittany F. ; Raje, Kapil R. ; Hottel, Benjamin A. ; Armisén, David ; Crumière, Antonin Jean Johan ; Refki, Peter Nagui ; Santos, Maria Emilia ; Sghaier, Essia ; Viala, Séverine ; Khila, Abderrahman ; Ahn, Seung-Joon ; Childers, Christopher ; Lee, Chien-Yueh ; Lin, Han ; Hughes, Daniel S. T. ; Duncan, Elizabeth J. ; Murali, Shwetha C. ; Qu, Jiaxin ; Dugan, Shannon ; Lee, Sandra L. ; Chao, Hsu ; Dinh, Huyen ; Han, Yi ; Doddapaneni, Harshavardhan ; Worley, Kim C. ; Muzny, Donna Marie ; Wheeler, David ; Panfilio, Kristen A. ; Vargas Jentzsch, Iris M. ; Vargo, Edward L. ; Booth, Warren ; Friedrich, Markus ; Weirauch, Matthew T. ; Anderson, Michelle A. ; Jones, Jeffery W. ; Mittapalli, Omprakash ; Zhao, Chaoyang ; Zhou, Jing-Jiang ; Evans, Jay D. ; Attardo, Geoffrey M. ; Robertson, Hugh M. ; Zdobnov, Evgeny M. ; Ribeiro, José M. C. ; Gibbs, Richard A. ; Werren, John H. ; Palli, Subba Reddy ; Schal, Coby ; Richards, Stephen
The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.
Alber, Thomas ; Appelshäuser, Harald ; Bächler, Joachim ; Bartke, Jerzy ; Białkowska, Helena ; Bieser, Fred ; Bloomer, Matthew A. ; Blyth, Charles O. ; Bock, Rudolf ; Bormann, Christian ; Brady, Franklin Paul ; Brockmann, Robert ; Bunčić, Predrag ; Caines, Helen Louise ; Cebra, Daniel A. ; Chan, Phaikying ; Cooper, Glenn E. ; Cramer, John G. ; Cramer, Pauline B. ; Csató, Péter ; Derado, Ivan ; Dunn, Jason ; Eckardt, Volker ; Eckhardt, Frank ; Euler, Sebastian ; Ferguson, M. I. ; Fischer, Hans Gerhard ; Fodor, Zoltán ; Foka, Panagiota ; Freund, Peter ; Fuchs, Matthias ; Gál, József ; Gaździcki, Marek ; Gładysz-Dziaduś, Ewa ; Grebieszkow, Jaroslaw ; Günther, Jörg ; Harris, John W. ; Heck, W. ; Hegyi, Sándor ; Hill, L. A. ; Huang, Isaac ; Howe, Mark A. ; Igo, George J. ; Irmscher, Detlef ; Jacobs, Peter Martin ; Jones, Peter Graham ; Kadija, Krešo ; Kecskemeti, J. ; Kowalski, Marek ; Kühmichel, Andreas ; Lasiuk, Brian ; Margetis, Spyridon ; Mitchell, J. W. ; Mock, Andreas ; Nelson, John M. ; Odyniec, Grazyna Janina ; Pálinkás, József ; Pálla, Gabriella ; Panagiotou, Apostolos D. ; Petridis, Athanasios ; Piper, Andreas ; Poskanzer, Arthur M. ; Prindle, Duncan J. ; Pühlhofer, Falk ; Rauch, Wolfgang Hans ; Renfordt, Rainer Arno Ernst ; Retyk, Waldemar ; Ritter, Hans Georg ; Röhrich, Dieter ; Rudolph, Heinrich ; Runge, Kay ; Sandoval, Andres ; Sann, Hans ; Schäfer, Erich ; Schmitz, Norbert ; Schönfelder, Stefan ; Seyboth, Peter ; Seyerlein, Jürgen ; Sikler, Ferenc ; Skrzypczak, Ewa ; Stock, Reinhard ; Ströbele, Herbert ; Szentpetery, Imre ; Sziklai, János ; Toy, Milton Y. ; Trainor, Thomas A. ; Trentalange, Stephen ; Vassiliou, Maria ; Vesztergombi, György ; Vranić, Danilo ; Wenig, Siegfried ; Whitten, Charles A. ; Wienold, Thomas ; Wood, Lindsay ; Zimanyi, József ; Zhu, X. -Z. ; Zybert, Ryszard