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41.
Makin OS Atkins E Sikorski P Johansson J Serpell LC 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(2):315-320
The molecular structure of the amyloid fibril has remained elusive because of the difficulty of growing well diffracting crystals. By using a sequence-designed polypeptide, we have produced crystals of an amyloid fiber. These crystals diffract to high resolution (1 A) by electron and x-ray diffraction, enabling us to determine a detailed structure for amyloid. The structure reveals that the polypeptides form fibrous crystals composed of antiparallel beta-sheets in a cross-beta arrangement, characteristic of all amyloid fibers, and allows us to determine the side-chain packing within an amyloid fiber. The antiparallel beta-sheets are zipped together by means of pi-bonding between adjacent phenylalanine rings and salt-bridges between charge pairs (glutamic acid-lysine), thus controlling and stabilizing the structure. These interactions are likely to be important in the formation and stability of other amyloid fibrils. 相似文献
42.
Maciej Tomaszewski James Eales Matthew Denniff Stephen Myers Guat Siew Chew Christopher P. Nelson Paraskevi Christofidou Aishwarya Desai Cara Büsst Lukasz Wojnar Katarzyna Musialik Jacek Jozwiak Radoslaw Debiec Anna F. Dominiczak Gerjan Navis Wiek H. van Gilst Pim van der Harst Nilesh J. Samani Stephen Harrap Pawel Bogdanski Ewa Zukowska-Szczechowska Fadi J. Charchar 《Journal of the American Society of Nephrology : JASN》2015,26(12):3151-3160
The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65×10−5) and diastolic BP (P=7.61×10−3) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0×10−3). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP. 相似文献
43.
Serruys PW García-García HM Buszman P Erne P Verheye S Aschermann M Duckers H Bleie O Dudek D Bøtker HE von Birgelen C D'Amico D Hutchinson T Zambanini A Mastik F van Es GA van der Steen AF Vince DG Ganz P Hamm CW Wijns W Zalewski A;Integrated Biomarker Imaging Study- Investigators 《Circulation》2008,118(11):1172-1182
44.
45.
Krzysztof Kaczmarek M.D. Jan Ruta M.D. Jerzy Wranicz M.D. Ph.D. Pawel Ptaszynski M.D. 《Annals of noninvasive electrocardiology》2014,19(5):501-503
Dual atrioventricular nodal nonreentrant tachycardia (DAVNNT) is very rarely observed clinically. The first review of this arrhythmia was published in 2011 by Wang, where four types of DAVNNT were described. Our case report presents a phenomenon that has never been published before. We revealed a very specific sequence of double fire phenomenon, 1:1 atrioventricular (AV) conduction and AV block. 相似文献
46.
Pawel Namsolleck Chiara Recarti Sébastien Foulquier Ulrike Muscha Steckelings Thomas Unger 《Current hypertension reports》2014,16(2):1-10
The converging clinical effectiveness of mineralocorticoid receptor antagonists (MRAs) Spironolactone and Eplerenone has made their safety profiles/cost-effectiveness key determinants of “agents of choice” across a broad range of clinical indications. The clinical biology of the aldosterone molecule and its range of effects in varied organ systems have been well elucidated from recent mechanistic and systematic studies. Clinical experience with Spironolactone is well established, as is its adverse effects profile. The range of adverse effects experienced with Spironolactone subsequently led to its modification and synthesis of Eplerenone. Recent published reports have confirmed lower prevalence rates of sex-related adverse effects attributable to Eplerenone compared to Spironolactone. There is, however, not much to choose between these agents in regards to other adverse effects including hyperkalemia and kidney failure. As was the experience with Spironolactone, as more robust observational data on Eplerenone accrues, it is possible that the real-life experience of its adverse profile may be discordant with that reported by randomized controlled clinical trials (RCTs). In addition, its metabolism by the vulnerable and highly polymorphic cytochrome dependent pathway also makes it susceptible to various drug interactions. The potential implication of the latter (including morbidity and mortality) may take years to evolve. 相似文献
47.
Meng Niu Brenda Morsey Benjamin G. Lamberty Katy Emanuel Fang Yu Rosiris Len-Rivera Joan W. Berman Peter J. Gaskill Stephanie M. Matt Pawel S. Ciborowski Howard S. Fox 《Viruses》2020,12(11)
Both substance use disorder and HIV infection continue to affect many individuals. Both have untoward effects on the brain, and the two conditions often co-exist. In the brain, macrophages and microglia are infectable by HIV, and these cells are also targets for the effects of drugs of abuse, such as the psychostimulant methamphetamine. To determine the interaction of HIV and methamphetamine, we isolated microglia and brain macrophages from SIV-infected rhesus monkeys that were treated with or without methamphetamine. Cells were subjected to single-cell RNA sequencing and results were analyzed by statistical and bioinformatic analysis. In the animals treated with methamphetamine, a significantly increased proportion of the microglia and/or macrophages were infected by SIV. In addition, gene encoding functions in cell death pathways were increased, and the brain-derived neurotropic factor pathway was inhibited. The gene expression patterns in infected cells did not cluster separately from uninfected cells, but clusters comprised of microglia and/or macrophages from methamphetamine-treated animals differed in neuroinflammatory and metabolic pathways from those comprised of cells from untreated animals. Methamphetamine increases CNS infection by SIV and has adverse effects on both infected and uninfected microglia and brain macrophages, highlighting the dual and interacting harms of HIV infection and drug abuse on the brain. 相似文献
48.
Diana Gassó Luca Rossi Gregorio Mentaberre Encarna Casas Roser Velarde Pawel Nosal Emmanuel Serrano Joaquim Segales Pedro Fernandez-Llario Carles Feliu 《Parasitology research》2014,113(9):3495-3500
Species of the Metastrongylus genus, the lung nematodes of pigs that require an intermediate host (earthworm) to complete their cycle, pose a potential risk to both livestock and humans. This parasite which can result in lung pathology and mixed infections with other pathogens (e.g. viruses) can be fatal to pigs. Although this genus is distributed worldwide, there are no classification keys for identifying this common parasite species. In this work, we take advantage of parasitological surveys of wild boar (Sus scrofa) in northern and central Spain and southern Poland to develop a morphological identification key for the five most common Metastrongylus species (Metastrongylus apri, Metastrongylus pudendotectus, Metastrongylus salmi, Metastrongylus confusus and Metastrongylus asymetricus). In addition, we provide the first record of M. confusus in Spain, probably unidentified until now due to the lack of appropriate identification keys. We hope that this user-friendly identification key will enable parasitologists and veterinary practitioners to avoid further misclassifications of Metastrongylus species. 相似文献
49.
50.
Martin Picard Jiangwen Zhang Saege Hancock Olga Derbeneva Ryan Golhar Pawel Golik Sean O’Hearn Shawn Levy Prasanth Potluri Maria Lvova Antonio Davila Chun Shi Lin Juan Carlos Perin Eric F. Rappaport Hakon Hakonarson Ian A. Trounce Vincent Procaccio Douglas C. Wallace 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(38):E4033-E4042