196,411 research outputs found
Dynamic ligand binding of dualsteric (allosteric/orthosteric) molecular probes controls the graded activation of muscarinic acetylcholine receptors
No full textWe investigated a class of bitopic (dualsteric) ligands of the M2 acetylcholine muscarinic receptor (M2AChR), i.e. compounds whose pharmacophoric groups are able to target the orthosteric as well as the allosteric binding site of the receptor.1,2 These model derivatives are composed of an allosteric fragment, an intermediate linker and an orthosteric moiety. As an example, ligands 1 and 2 incorporate the molecular portion of the allosteric compound Naphmethonium and the potent muscarinic agonist Iperoxo, which are connected by a flexible or a rigidified spacer group, respectively (Figure 1). These bipharmacophoric molecular probes were found to switch between two different binding orientations, resulting in both active and inactive populations of receptors bound by a given ligand, a behavior that has been termed dynamic ligand binding.3
Figure 1
In this study, pharmacological data analysis and computational simulations based on active and inactive M2AChR crystal structures led to identify two distinct binding topographies in a group of dualsteric partial agonists. One binding mode, which resembled that of the co-crystallized orthosteric ligand Iperoxo, engendered an agonist response. Conversely, dualsteric ligands binding to the allosteric site only showed a receptor-complex comparable to that of allosteric modulators. Thus, the observed agonist efficacies depended on the fraction of dualsteric (i.e. active) vs. purely allosteric (i.e. inactive) binding modes.4
References
1. Antony, J.; Kellershon, K.; Mohr-Andrä, M.; Kebig, A.; Prilla, S.; Muth, M.; Heller, E.; Disingrini, T.; Dallanoce, C.; Bertoni, S.; Schrobang, J.; Tränkle, C.; Kostenis, E.; Christopoulos, A.; Höltje, H.-D.; Barocelli, E.; De Amici, M.; Holzgrabe, U.; Mohr, K. FASEB J. 2009, 23, 442-450.
2. Bock, A.; Merten, N.; Schrage, R.; Dallanoce, C.; Bätz, J.; Klöckner, J.; Schmitz, J.; Matera, C.; Simon, K.; Kebig, A.; Peters, L.; Müller, A.; Schrobang-Ley, J.; Tränkle, C.; Hoffmann, C.; De Amici, M.; Holzgrabe, U.; Kostenis, E.; Mohr; K. Nat. Commun. 2012, 3:1044, doi: 10.1038/ncomms2028.
3. Bock, A.; Chirinda, B.; Krebs, F.; Messerer, R.; Bätz, J.; Muth, M.; Dallanoce, C.; Klingenthal, D.; Tränkle, C.; Hoffmann, C.; De Amici, M.; Holzgrabe, U.; Kostenis, E.; Mohr, K. Nat. Chem. Biol. 2014, 10, 18-20.
4. Bock, A.; Bermudez, M.; Krebs, F.; Matera, C.; Chirinda, B.; Sydow, D.; Dallanoce, C.; Holzgrabe, H.; De Amici, M.; Lohse, M.; Wolber, G.; Mohr, K. J. Biol. Chem., in press
Intramedullary cavernoma: a surgical resection technique
No full textIntramedullary spinal cavernoma is a rare vascular disease constituting 5-12% of all spinal vascular tumors. The clinical course is usually characterized either by an acute neurological deterioration, recurrent episodes of neurological deficits or by a slowly progressive neurological decline. Microsurgical removal is recommended when the symptoms become clinically relevant and the lesion appears accessible. In this article, we present a surgical technique to completely resect an intramedullary cavernoma with the aid of intraoperative electrophysiological monitoring and intraoperative real-time ultrasound guidance. A brief description of current management of this pathology is also presented
Peculiarities of Use of Progressive Methods of Teaching Choreographic Disciplines in the Conditions of Pedagogical Activity of A. M. Messerer
No full textУ статті висвітлено та узагальнено професійну діяльність Асафа Михайловича Мессерера, досліджується питання необхідності постійного пошуку та застосування прогресивних ідей і методів навчання хореографічних дисциплін, які сприяють розвитку історії мистецтва в цілому. На основі досягнень професійної діяльності балетмейстера 20-го ст. розвивається та збагачується теорія та методика викладання класичного танцю та поява подальших напрямів хореографічних дисциплін. Доведено, що науково-педагогічна діяльність А. М. Мессерера – це інтелектуальна творча Діяльність, що спрямована на здобуття й використання нових теоретичних знань з практичним підґрунтям.The article highlights and generalizes peculiarities of use of progressive methods of teaching choreographic disciplines on the example of vital, creative and pedagogical activity of A. M. Messerer. To achieve the goal, a set of methods, in particular general scientific (analysis, synthesis, generalization, systematization), which were used to determine the state of development of the problem and characteristics of progressive methods of teaching choreographic disciplines in the conditions of A. S. Messerer's professional activity and specific scientific (biographical, historical-genetic and retrospective analysis), which allowed to highlight life and creative path of Asaf Messerer and his contribution to development of choreographic education.
Based on historical and scientific works of choreographic art researchers, enrichment of teaching methods, teaching techniques and system of classical dance during the choreographer's teaching have been highlighted. Progressive methods of teaching choreographic disciplines, which enriched the system of classical dance with their existence, opened new names of classical ballet teachers, students, performers of the main parties in ballet performances by the choreographer during his pedagogical work have been revealed. The teachers-followers of the teaching system of A. Messerer, who adopted pedagogical background of the choreographer, are characterized.
It has been found out that in the process of their activity pedagogues, choreographers, choreographers, dancers should all the time be in search of new teaching methods, but take into account the canons and methods of teaching formed for many years.
The study does not exhaust all the aspects of the problem and requires further research and search for new methods of teaching choreographic disciplines in choreographic education
Dietary supplements : trends, demographics and mortality among users
No full textDietary supplements have received growing attention in society and sales numbers indicate increased use. Still, time trends in prevalence of users have been unknown. In order to accurately explore associations between diet and diseases, valid assessment methods for micronutrient intake from foods and dietary supplements are needed.The prevalence of dietary supplement users in Sweden, estimated in three nationally representative surveys, conducted during the last decades, increased by 70% and was 22% and 33% for men and women, respectively, in 1997. Use of natural remedies increased threefold. The increase was observed in all age groups, all socio-economic groups, and all parts of Sweden. The use of these preparations was associated with several sociodemographic and health behaviour factors. The best predictors of use were age, sex and subjective health. Women and older individuals were more likely to be users as well as people reporting a poor health status. Subjects who were underweight and subjects reporting moderate to high levels of exercise were also more often users.To evaluate if a self-reported food frequency questionnaire (FFQ) can measure use of dietary supplements and the total micronutrient intake, sensitivity, specificity and validity was compared to fourteen 24-hour recalls (collected monthly by telephone) in 248 men (40-75 years old) in a random sample from central Sweden. The sensitivity of the FFQ for measuring use of dietary supplements was 78% and the specificity 93%. Validity for micronutrient intake (Spearman correlation coefficients) increased by 13% (from 0.49 to 0.62), when nutrients from supplements were included. The classification of micronutrient intake from the FFQ into corresponding quintile in the 24-hour recalls was also improved from 37% to 5 1 % when supplements were included. The average reproducibility (intraclass correlation coefficients) for total nutrient intake was 0.61 between two FFQs completed one year apart. The observed increase in the validity of micronutrient estimates due to inclusion of supplements has important implications for epidemiological studies.In a population-based prospective cohort of 48,645 Swedish men, we investigated the association between use of dietary supplement and all-cause, cardiovascular and cancer mortality. By linking the cohort to the Death Register and the Register of Causes of Death, 2499 deaths (all cause) was ascertained during 246,522 person-years of follow-up, while 540 deaths occurred due to cardiovascular diseases and 398 deaths due to cancer during 153,796 person-years of follow-up for the specific cause mortality. In the multivariate adjusted model, there was no association observed between use of dietary supplements and all-cause mortality, cardiovascular or cancer mortality. However, both confounding and reversed causality seemed to be important issues to consider in this type of study. Independent of adjusting for several lifestyle factors, there was still an adverse association among former smokers, between regular use of dietary supplements and all-cause mortality and a suggested association among current smokers.In conclusion, the use of dietary supplements is associated with several lifestyle factors and the prevalence of users has increased during the last decades. Thus, use of dietary supplements has to be considered in nutritional surveys and when assessing associations between diet and diseases. The adverse association found between use of dietary supplements and mortality among former/current smokers needs further evaluation.List of scientific papersI. Messerer M, Johansson SE, Wolk A (2001). "Use of dietary supplements and natural remedies increased dramatically during the 1990s." J Intern Med 250(2): 160-6 https://pubmed.ncbi.nlm.nih.gov/11489066II. Messerer M, Johansson SE, Wolk A (2001). "Sociodemographic and health behaviour factors among dietary supplement and natural remedy users." Eur J Clin Nutr 55(12): 1104-10 https://pubmed.ncbi.nlm.nih.gov/11781678III. Messerer M, Wolk A (2004). "Sensitivity and specificity of self-reported use of dietary supplements. " Eur J Clin Nutr Jun 30 : Epub ahead of print https://pubmed.ncbi.nlm.nih.gov/15226758IV. Messerer M, Johansson SE, Wolk A (2004). "The validity of questionnaire-based micronutrient intake estimates is increased by including dietary supplement use in Swedish men." J Nutr 134(7): 1800-5 https://pubmed.ncbi.nlm.nih.gov/15226472V. Messerer M, Hakansson N, Wolk A, Akesson A (2004). "Dietary supplement use and mortality in a cohort of Swedish men." (Manuscript)</p
Intracranial pressure and outcome in critically ill patients with aneurysmal subarachnoid hemorrhage : a systematic review
No full textBACKGROUND: Evidences supporting the use of intracranial pressure (ICP) monitoring after aneurysmal subarachnoid hemorrhage (aSAH) are limited. The aim of our paper was to examine whether elevated intracranial pressure and ICP- derived variables predict mortality and functional outcomes after aSAH. EVIDENCE ACQUISITION: A systematic review of the literature was performed through PubMed and Cochrane databases up to June 2015. Population was restricted to aSAH patients requiring admission to the intensive care unit. ICP was included in the analysis as absolute value as well as variables derived from ICP monitoring (pressure reactivity index. ICP pulse wave amplitude. ICP-arterial blood pressure wave amplitude correlation and ICP variability). Outcomes included mortality, neurological recovery and delayed cerebral ischemia (DCI). Quality of evidence was rated using the GRADE system. EVIDENCE SYNTHESIS: Twenty-six studies were examined. Due to heterogeneity in qualifying studies, a meta-anal- ysis could not be generated. We found a correlation between elevated ICP and mortality. However. ICP absolute values were not independent predictors of long-term functional outcomes (low quality of evidence). A variable relationship between elevated ICP and DCI was found (very low quality of evidence). ICP-derived variables had higher accuracy than ICP absolute values in predicting functional outcomes (moderate quality of evidence). CONCLUSIONS: Elevated ICP was associated with higher mortality however absolute ICP values per se were not independent predictors of functional recovery. Variables derived from ICP monitoring are more accurate than ICP absolute values in predicting outcome. Given the absence of good quality data, additional large studies may help to better define the prognostic value of ICP after aSAH
Dr. Duane M. Jackson, Morehouse College, July 2011
No full textThis video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer
"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States" By M. Carey.
No full text"Reflections on the subject of Emigration from Europe with a view to Settlement in the United States: containing bried sketches of the moral and political character of those states.
By M. Carey, member of the American philosophical, and of the American Antiquarian Society, and author of The Olive Branch, Cindiciae Hibernicae, essays on banking, on political economy, and on internal improvement.
To which are now added the English editor's comments on the subject; together with Important Advice to Emigrants, and Cautions Against Impositions Practiced in the Outports
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Dr. Glendon Swarthout
No full textHosted by Roger M. Busfield, MSU Assistant Professor of Speech and Theater, Meet the Author is designed to introduce a general audience to a contemporary author and their work through in-depth interviews. This episode features a conversation between Dr. Glendon Swarthout, prolific author and English professor at MSU, and assistant professors Sam S. Baskett and Theodore B. Strandness
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