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  • International Union of Crystallography (IUCr)  (15)
  • American Association for the Advancement of Science (AAAS)  (4)
  • American Heart Association (AHA)  (3)
Document type
  • 1
    Publication Date: 2012-07-20
    Description: Objective— The postural tachycardia syndrome (POTS) has multiple symptoms, chief among which are tachycardia, weakness, and recurrent blackouts while standing. Previous research has implicated dysfunction of the norepinephrine transporter. A coding mutation in the norepinephrine transporter gene ( SLC6A2 ) sequence has been reported in 1 family kindred only. The goal of the present study was to further characterize the role and regulation of the SLC6A2 gene in POTS. Methods and Results— Sympathetic nervous system responses to head-up tilt were examined by combining norepinephrine plasma kinetics measurements and muscle sympathetic nerve activity recordings in patients with POTS compared with that in controls. The SLC6A2 gene sequence was investigated in leukocytes from POTS patients and healthy controls using single nucleotide polymorphisms genotyping, bisulphite sequencing, and chromatin immunoprecipitation assays for histone modifications and binding of the transcriptional regulatory complex, methyl-CpG binding protein 2. The expression of norepinephrine transporter was lower in POTS patients compared with healthy volunteers. In the absence of altered SLC6A2 gene sequence or promoter methylation, this reduced expression was directly correlated with chromatin modifications. Conclusion— We propose that chromatin-modifying events associated with SLC6A2 gene suppression may constitute a mechanism of POTS.
    Keywords: Gene regulation, Genomics, Other etiology
    Print ISSN: 1079-5642
    Electronic ISSN: 1524-4636
    Topics: Medicine
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  • 2
    Publication Date: 2011-04-30
    Description: Stem cells cycle through active and quiescent states. Large populations of stem cells in an organ may cycle randomly or in a coordinated manner. Although stem cell cycling within single hair follicles has been studied, less is known about regenerative behavior in a hair follicle population. By combining predictive mathematical modeling with in vivo studies in mice and rabbits, we show that a follicle progresses through cycling stages by continuous integration of inputs from intrinsic follicular and extrinsic environmental signals based on universal patterning principles. Signaling from the WNT/bone morphogenetic protein activator/inhibitor pair is coopted to mediate interactions among follicles in the population. This regenerative strategy is robust and versatile because relative activator/inhibitor strengths can be modulated easily, adapting the organism to different physiological and evolutionary needs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321266/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321266/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Plikus, Maksim V -- Baker, Ruth E -- Chen, Chih-Chiang -- Fare, Clyde -- de la Cruz, Damon -- Andl, Thomas -- Maini, Philip K -- Millar, Sarah E -- Widelitz, Randall -- Chuong, Cheng-Ming -- AR47364/AR/NIAMS NIH HHS/ -- AR60306/AR/NIAMS NIH HHS/ -- R01 AR042177/AR/NIAMS NIH HHS/ -- R01 AR042177-17/AR/NIAMS NIH HHS/ -- R01 AR042177-18/AR/NIAMS NIH HHS/ -- R01 AR060306/AR/NIAMS NIH HHS/ -- R01 AR060306-02/AR/NIAMS NIH HHS/ -- R01 AR060306-03/AR/NIAMS NIH HHS/ -- R01-AR42177/AR/NIAMS NIH HHS/ -- R01-AR47709/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2011 Apr 29;332(6029):586-9. doi: 10.1126/science.1201647.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Southern California (USC), Los Angeles, CA 90033, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21527712" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Morphogenetic Proteins/*metabolism ; Computer Simulation ; Hair Follicle/*cytology/*growth & development/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Models, Biological ; Rabbits ; *Regeneration ; *Signal Transduction ; Stem Cells/*physiology ; Stochastic Processes ; Wnt Proteins/*metabolism
    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
    Publication Date: 2011-07-19
    Description: Brown rot decay removes cellulose and hemicellulose from wood--residual lignin contributing up to 30% of forest soil carbon--and is derived from an ancestral white rot saprotrophy in which both lignin and cellulose are decomposed. Comparative and functional genomics of the "dry rot" fungus Serpula lacrymans, derived from forest ancestors, demonstrated that the evolution of both ectomycorrhizal biotrophy and brown rot saprotrophy were accompanied by reductions and losses in specific protein families, suggesting adaptation to an intercellular interaction with plant tissue. Transcriptome and proteome analysis also identified differences in wood decomposition in S. lacrymans relative to the brown rot Postia placenta. Furthermore, fungal nutritional mode diversification suggests that the boreal forest biome originated via genetic coevolution of above- and below-ground biota.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eastwood, Daniel C -- Floudas, Dimitrios -- Binder, Manfred -- Majcherczyk, Andrzej -- Schneider, Patrick -- Aerts, Andrea -- Asiegbu, Fred O -- Baker, Scott E -- Barry, Kerrie -- Bendiksby, Mika -- Blumentritt, Melanie -- Coutinho, Pedro M -- Cullen, Dan -- de Vries, Ronald P -- Gathman, Allen -- Goodell, Barry -- Henrissat, Bernard -- Ihrmark, Katarina -- Kauserud, Havard -- Kohler, Annegret -- LaButti, Kurt -- Lapidus, Alla -- Lavin, Jose L -- Lee, Yong-Hwan -- Lindquist, Erika -- Lilly, Walt -- Lucas, Susan -- Morin, Emmanuelle -- Murat, Claude -- Oguiza, Jose A -- Park, Jongsun -- Pisabarro, Antonio G -- Riley, Robert -- Rosling, Anna -- Salamov, Asaf -- Schmidt, Olaf -- Schmutz, Jeremy -- Skrede, Inger -- Stenlid, Jan -- Wiebenga, Ad -- Xie, Xinfeng -- Kues, Ursula -- Hibbett, David S -- Hoffmeister, Dirk -- Hogberg, Nils -- Martin, Francis -- Grigoriev, Igor V -- Watkinson, Sarah C -- New York, N.Y. -- Science. 2011 Aug 5;333(6043):762-5. doi: 10.1126/science.1205411. Epub 2011 Jul 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉College of Science, University of Swansea, Singleton Park, Swansea SA2 8PP, UK. d.c.eastwood@swansea.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21764756" target="_blank"〉PubMed〈/a〉
    Keywords: Angiosperms/microbiology ; Basidiomycota/classification/enzymology/*genetics/physiology ; *Biodiversity ; Biological Evolution ; Biota ; Cell Wall/*metabolism ; Coniferophyta/microbiology ; Coriolaceae/enzymology/genetics/physiology ; Gene Expression Profiling ; Genes, Fungal ; Genomics ; Lignin/metabolism ; Mycorrhizae/enzymology/*genetics/physiology ; Oxidoreductases/genetics/metabolism ; Peroxidases/genetics/metabolism ; Phylogeny ; Proteome ; Symbiosis ; Trees/*microbiology ; Wood/metabolism/*microbiology
    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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  • 4
    Publication Date: 2016-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burke, M -- Craxton, M -- Kolstad, C D -- Onda, C -- Allcott, H -- Baker, E -- Barrage, L -- Carson, R -- Gillingham, K -- Graff-Zivin, J -- Greenstone, M -- Hallegatte, S -- Hanemann, W M -- Heal, G -- Hsiang, S -- Jones, B -- Kelly, D L -- Kopp, R -- Kotchen, M -- Mendelsohn, R -- Meng, K -- Metcalf, G -- Moreno-Cruz, J -- Pindyck, R -- Rose, S -- Rudik, I -- Stock, J -- Tol, R S J -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):292-3. doi: 10.1126/science.aad9634. Epub 2016 Apr 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stanford University, Stanford, CA, USA. ; Stanford University, Stanford, CA, USA. ckolstad@stanford.edu. ; New York University, New York, NY, USA. ; University of Massachusetts, Amherst, MA, USA. ; Brown University, Providence, RI, USA. ; University of California, San Diego, CA, USA. ; Yale University, New Haven, CT, USA. ; University of Chicago, Chicago, IL, USA. ; World Bank, Washington, DC, USA. ; Arizona State University, Tempe, AZ, USA. ; Columbia University, New York, NY, USA. ; University of California, Berkeley, CA, USA. ; Northwestern University, Evanston, IL, USA. ; University of Miami, Coral Gables, FL, USA. ; Resources for the Future, Washington, DC, USA. ; University of California, Santa Barbara, CA, USA. ; Tufts University, Medford, MA, USA. ; Georgia Institute of Technology, Atlanta, GA, USA. ; Massachusetts Institute of Technology, Cambridge, MA, USA. ; Electric Power Research Institute, Palo Alto, CA, USA. ; Iowa State University, Ames, IA, USA. ; Harvard University, Cambridge, MA, USA. ; University of Sussex, Falmer, UK, and Vrije Universiteit Amsterdam, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081055" target="_blank"〉PubMed〈/a〉
    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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  • 5
    Publication Date: 2014-08-14
    Description: More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks’ gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks’ gestation, the consumption of ≥3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70–0.77) and 0.68 (0.63–0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss 〈10 weeks, and mean uterine artery resistance index (area under the receiver operator curve [95% confidence interval] in training and validation cohorts, 0.89 [0.78–1.0] and 0.78 [0.58–0.99], respectively). Neither model included pregnancy-associated plasma protein A, previously reported to predict preeclampsia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preeclampsia.
    Keywords: Other hypertension, Clinical Studies
    Print ISSN: 0194-911X
    Topics: Medicine
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  • 6
    Publication Date: 2015-07-21
    Description: Background— Aspirin is the most widely used antiplatelet drug postmyocardial infarction, yet its optimal maintenance dose after percutaneous coronary intervention with stenting remains uncertain. Methods and Results— We compared outcomes of 10 213 patients with myocardial infarction who underwent percutaneous coronary intervention and were discharged on dual-antiplatelet therapy at 228 US hospitals in the Treatment with ADP Receptor Inhibitors: Longitudinal Assessment of Treatment Patterns and Events after Acute Coronary Syndrome (TRANSLATE-ACS) study from 2010 to 2012. Major adverse cardiovascular events and bleeding within 6 months postdischarge were compared between high-dose (325 mg) and low-dose aspirin (81 mg) by using regression models with inverse probability-weighted propensity adjustment. Overall, 6387 patients (63%) received high-dose aspirin at discharge. Major adverse cardiovascular events risk was not significantly different between groups (high versus low: unadjusted 8.2% versus 9.2%; adjusted hazard ratio, 0.99; 95% confidence interval, 0.85–1.17). High-dose aspirin use was associated with greater risk of any Bleeding Academic Research Consortium–defined bleeding events (unadjusted 24.2% versus 22.7%; adjusted odds ratio, 1.19; 95% confidence interval, 1.06–1.33), driven mostly by minor Bleeding Academic Research Consortium type 1 or 2 bleeding events not requiring hospitalization (unadjusted 21.4% versus 19.5%; adjusted odds ratio, 1.19; 95% confidence interval, 1.05–1.34). Bleeding events requiring hospitalization were similar by aspirin dosing groups (unadjusted 2.8% versus 3.2%, adjusted odds ratio, 1.22; 95% confidence interval, 0.87–1.70). Similar associations were observed in landmark analyses accounting for aspirin dosing change over time, and across subgroup analyses by age, sex, baseline aspirin use, and type of ADP receptor inhibitor (clopidogrel versus prasugrel/ticagrelor). Conclusions— Among percutaneous coronary intervention–treated patients with myocardial infarction, high-maintenance-dose aspirin was associated with similar rates of major adverse cardiovascular events, but a greater risk of minor bleeding than those discharged on low-dose aspirin.
    Keywords: Health policy and outcome research
    Electronic ISSN: 1524-4539
    Topics: Medicine
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  • 7
    Electronic Resource
    Electronic Resource
    Copenhagen : International Union of Crystallography (IUCr)
    Acta crystallographica 50 (1994), S. 302-316 
    ISSN: 1399-0047
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: The three-dimensional structure of human dicupric monooxalate lactoferrin, Cu2oxLf, has been determined to 2.0 Å resolution, using X-ray diffraction data collected by diffractometry to 2.5 Å resolution, and oscillation photography on a synchrotron source to 2.0 Å resolution. Difference electron-density maps calculated between Cu2oxLf and both dicupric lactoferrin, Cu2Lf, and diferric lactoferrin, Fe2Lf, showed that the oxalate had replaced a carbonate in the C-terminal binding site, and that, relative to Cu2Lf, there were no significant differences in the N-terminal site. The structure was then refined crystallographically by restrained least-squares methods. The final model, in which the r.m.s. deviation in bond distances is 0.017 Å, contains 5314 protein atoms (691 residues), two Cu2+ ions, one bicarbonate ion, one oxalate ion, 325 solvent molecules and one sugar residue. The crystallographic R factor of 0.193 is for 46 134 reflections in the range 8.0 to 2.0 Å resolution. The oxalate ion is coordinated to copper in a 1,2-bidentate fashion, and the added bulk of the anion results in the rearrangement of the side chains of nearby arginine and tyrosine residues. No other major alterations in the molecule can be observed, the overall protein structure being the same as that for Cu2Lf and Fe2Lf.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Copenhagen : International Union of Crystallography (IUCr)
    Acta crystallographica 50 (1994), S. 429-440 
    ISSN: 1399-0047
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: In protein crystallography, the initial experimental problem is the identification of physical and chemical conditions that will support nucleation and crystal growth. Ideally, experiments to search for such conditions would be based on a full-factorial structure, with variation in the temperature and solution composition. However, consideration of even a moderate number of possibilities for the composition of the system will result in factorial experiments which may be prohibitively large. In this paper it is proposed that search experiments for protein crystallization might be based on orthogonal arrays. These are subsets of full-factorial experiments which possess a great deal of symmetry, such that a uniform distribution of points throughout the experimental region is preserved. Such experiments have reasonable size, explore the proposed experimental region in a systematic fashion, and form a logical basis for a sequential approach to the search for crystallization conditions. Examples of such initial search experiments are given, and their application to some recent protein crystallization problems in this laboratory is described briefly. The relationship of this approach to other protein crystallization search procedures is also discussed.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1399-0047
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: The structure of cytochrome c′ from two bacterial species, Alcaligenes sp and Alcaligenes denitrificans, have been determined from X-ray diffraction data to 3.0 Å resolution using the anomalous scattering of the single Fe atom in each to identify and refine a weak molecular-replacement solution. Molecular-replacement studies, with the program AMORE, used two isomorphous data sets (from the two species), two independent search models (the cytochromes c′ from Rhodospirillum molischianum and Rhodospirillum rubrum), both with and without side chains, and two different resolution ranges (10.0–4.0 and 15.0–3.5Å) to generate a large number of potential solutions. No single solution stood out and none appeared consistently. The Fe-atom position in each structure was then determined from its anomalous-scattering contribution and all molecular- replacement solutions were discarded which did not (i) place the Fe atom correctly and (ii) orient the molecule such that a crystallographic twofold axis generated a dimer like those of the two search models. Finally, electron-density maps phased solely by the Fe-atom anomalous scattering were calculated. As these were combined and subjected to solvent flattening and histogram matching (with the program SQUASH), correlation with the remaining molecular-replacement solutions identified one as correct and enabled it to be improved and subjected to preliminary refinement. The correctness of the solution is confirmed by parallel isomorphous-replacement studies.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1399-0047
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: The iron-dependent alcohol dehydrogenase from Zymomonas mobilis has been crystallized in a form suitable for X-ray diffraction studies. The crystals grew in hanging drops by vapor diffusion, equilibrating with a solution comprising 25–27% methoxypolyethylene glycol 5000 and 1 mM Co2+ in a 0.2 M succinic acid/potassium hydroxide buffer at pH 5.5–5.7 at 281 K. Crystals are tetragonal, P4122 (or P4322), with unit-cell dimensions a = b = 125.7, c = 248.1 Å. Four molecules comprise the asymmetric unit, and a self-rotation function indicates twofold local symmetry perpendicular to the unique axis and 15° from a crystallographic twofold axis. Diffraction data to 3.0 Å have been collected.
    Type of Medium: Electronic Resource
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