Model evaluation of the radiative and temperature effects of the ozone content changes in the global atmosphere of 1980's

Radiative and temperature effects of the observed ozone and greenhouse gas atmospheric content changes in 1980 - 1990 are evaluated using the two-dimensional energy balance radiative-convective model of the zonally and annually averaged troposphere and stratosphere. Calculated radiative flux changes for standard conditions quantitatively agree with their estimates in WMO/UNEP 1991 review. Model estimates indicate rather small influence of ozone depletion in the lower stratosphere on the greenhouse tropospheric warming rate, being more significant in the non-tropical Southern Hemisphere. The calculated cooling of the lower stratosphere is close to the observed temperature trends there in the last decade

DrugBank 3.0: a comprehensive resource for ‘Omics’ research on drugs

DrugBank (http://www.drugbank.ca) is a richly annotated database of drug and drug target information. It contains extensive data on the nomenclature, ontology, chemistry, structure, function, action, pharmacology, pharmacokinetics, metabolism and pharmaceutical properties of both small molecule and large molecule (biotech) drugs. It also contains comprehensive information on the target diseases, proteins, genes and organisms on which these drugs act. First released in 2006, DrugBank has become widely used by pharmacists, medicinal chemists, pharmaceutical researchers, clinicians, educators and the general public. Since its last update in 2008, DrugBank has been greatly expanded through the addition of new drugs, new targets and the inclusion of more than 40 new data fields per drug entry (a 40% increase in data ‘depth’). These data field additions include illustrated drug-action pathways, drug transporter data, drug metabolite data, pharmacogenomic data, adverse drug response data, ADMET data, pharmacokinetic data, computed property data and chemical classification data. DrugBank 3.0 also offers expanded database links, improved search tools for drug–drug and food–drug interaction, new resources for querying and viewing drug pathways and hundreds of new drug entries with detailed patent, pricing and manufacturer data. These additions have been complemented by enhancements to the quality and quantity of existing data, particularly with regard to drug target, drug description and drug action data. DrugBank 3.0 represents the result of 2 years of manual annotation work aimed at making the database much more useful for a wide range of ‘omics’ (i.e. pharmacogenomic, pharmacoproteomic, pharmacometabolomic and even pharmacoeconomic) applications

Age-Related Attenuation of Dominant Hand Superiority

The decline of motor performance of the human hand-arm system with age is well-documented. While dominant hand performance is superior to that of the non-dominant hand in young individuals, little is known of possible age-related changes in hand dominance. We investigated age-related alterations of hand dominance in 20 to 90 year old subjects. All subjects were unambiguously right-handed according to the Edinburgh Handedness Inventory. In Experiment 1, motor performance for aiming, postural tremor, precision of arm-hand movement, speed of arm-hand movement, and wrist-finger speed tasks were tested. In Experiment 2, accelerometer-sensors were used to obtain objective records of hand use in everyday activities

Gene therapy of mass pathologies

Описан комплекс исследований, которым позволяет пройти путь от идеи до экспериментального решения принципиальной возможности генной терапии массовых патологий, на примере инсулинзависимого сахарного диабета и атеросклероза. Произведен подбор и анализ регуляторных элементов, которые позволяют осуществлять экспрессию экзогенных генов независимо от состояния общей клеточной регуляции . На клетках различных тканей и организмов, а также in vivo показано экспрессию генетического материала , вводимого (как модельного гена бактериальной β-галактозидазы, так и генов инсулина и аполипопротеина высокой плотности Al, которые имеют отношение к вышеупомянутым патологий ) . Отмечено неправомерность экстраполяции результатов, полученных в культуре клеток, на животных; показано неоднозначность экспрессии рекомбинантных молекул в зависимости от генного окружения и типа клеток реципиентов. Как в культуре клеток, так и в организму обнаружено индивидуально– клеточную гетерогенность количественных характеристик экспрессии : введенного извне гена. Кроме того, отмечено индивидуально – организменном и возрастную гетерогенность экспрессии экзогенной информации. Сделан вывод о необходимости индивидуализации генной терапии массовых патологов .Описано комплекс досліджень, яким дозволяє пройти шлях від ідеї до експериментального вирішення принципової можливості генної терапії масових патологій, на прикладі інсулінзалежного цукрового діабету та атеросклерозу. Зроблено добір та аналіз регуляторних елементів, які дозволяють здійснювати експресію екзогенних генів незалежно від стану загальної клітинної регуляції. На клітинах різних тканин та організмів, а також in vivo показано експресію генетичного матеріалу, що вводиться (як модельного гена бактеріальної β-галактозидази, так і генів інсуліну та аполіпопротеїну високої щільності Al, які мають відношення до вищезгаданих патологїй). Відзначено неправомірність екстраполяції результатів, отриманих в культурі клітин, на тварин; показано неоднозначність експресії рекомбінантних молекул залежно від генного оточення і типу клітин реципієнтів. Як в культурі клітин, так і в організмові виявлено індивідуально-клітинну гетерогенність кількісних характеристик експресі: введеного ззовні гена. Крім того, відзначено індивідуально-організмову та вікову гетерогенність експресії екзогенної інформації. Зроблено висновок про необхідність індивідуалізації генної терапії масових патологів.The whole complex of investigations is described that allows to run the way from the idea to experimental realization of a fundamental possibility of gene therapy and its application to mass pathologies on the sample of insulin-dependent diabetes and atherosclerosis. The search and analysis were performed of such regulatory elements that would permit an expression irrespective of the state of a general cell regulation. Expression of the implanted gene material is shown on cells of different tissues and different organisms and also in vivo (both the model gene of β-galactosidase Escherichia coli and insulin- and apolipoprotein high density Al-coding genes related to above stated pathologies). It is concluded that the results obtained in the culture outside the organisms shouldn't be extrapolated on the animals, i. e. on the organism's level. The expression of recombinant molecules is shown to be ambiguous and depend on gene's surroundings and the type of recipient cells. Both in the culture and in the organism the individual cell heterogeneity is observed in the quantitative characteristics of the expression of gene implanted from outside. Besides, an individual organism and age heterogeneity with regard to the expression of the exogenous gene is reported. The conclusion is made about the necessity to individualize gene therapy of mass pathologies

KB-Rank: efficient protein structure and functional annotation identification via text query

The KB-Rank tool was developed to help determine the functions of proteins. A user provides text query and protein structures are retrieved together with their functional annotation categories. Structures and annotation categories are ranked according to their estimated relevance to the queried text. The algorithm for ranking first retrieves matches between the query text and the text fields associated with the structures. The structures are next ordered by their relative content of annotations that are found to be prevalent across all the structures retrieved. An interactive web interface was implemented to navigate and interpret the relevance of the structures and annotation categories retrieved by a given search. The aim of the KB-Rank tool is to provide a means to quickly identify protein structures of interest and the annotations most relevant to the queries posed by a user. Informational and navigational searches regarding disease topics are described to illustrate the tool’s utilities. The tool is available at the URL http://protein.tcmedc.org/KB-Rank

Does the routine use of global coronary heart disease risk scores translate into clinical benefits or harms? A systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>Guidelines now recommend routine assessment of global coronary heart disease (CHD) risk scores. We performed a systematic review to assess whether global CHD risk scores result in clinical benefits or harms.</p> <p>Methods</p> <p>We searched MEDLINE (1966 through June 13, 2007) for articles relevant to our review. Using predefined inclusion and exclusion criteria, we included studies of any design that provided physicians with global risk scores or allowed them to calculate scores themselves, and then measured clinical benefits and/or harms. Two reviewers reviewed potentially relevant studies for inclusion and resolved disagreement by consensus. Data from each article was then abstracted into an evidence table by one reviewer and the quality of evidence was assessed independently by two reviewers.</p> <p>Results</p> <p>11 studies met criteria for inclusion in our review. Six studies addressed clinical benefits and 5 addressed clinical harms. Six studies were rated as "fair" quality and the others were deemed "methodologically limited". Two fair quality studies showed that physician knowledge of global CHD risk is associated with increased prescription of cardiovascular drugs in high risk (but not all) patients. Two additional fair quality studies showed no effect on their primary outcomes, but one was underpowered and the other focused on prescribing of lifestyle changes, rather than drugs whose prescribing might be expected to be targeted by risk level. One of these aforementioned studies showed improved blood pressure in high-risk patients, but no improvement in the proportion of patients at high risk, perhaps due to the high proportion of participants with baseline risks significantly exceeding the risk threshold. Two fair quality studies found no evidence of harm from patient knowledge of global risk scores when they were accompanied by counseling, and optional or scheduled follow-up. Other studies were too methodologically limited to draw conclusions.</p> <p>Conclusion</p> <p>Our review provides preliminary evidence that physicians' knowledge of global CHD risk scores may translate into modestly increased prescribing of cardiovascular drugs and modest short-term reductions in CHD risk factors without clinical harm. Whether these results are replicable, and translate across other practice settings or into improved long-term CHD outcomes remains to be seen.</p

GIT2 Acts as a Potential Keystone Protein in Functional Hypothalamic Networks Associated with Age-Related Phenotypic Changes in Rats

The aging process affects every tissue in the body and represents one of the most complicated and highly integrated inevitable physiological entities. The maintenance of good health during the aging process likely relies upon the coherent regulation of hormonal and neuronal communication between the central nervous system and the periphery. Evidence has demonstrated that the optimal regulation of energy usage in both these systems facilitates healthy aging. However, the proteomic effects of aging in regions of the brain vital for integrating energy balance and neuronal activity are not well understood. The hypothalamus is one of the main structures in the body responsible for sustaining an efficient interaction between energy balance and neurological activity. Therefore, a greater understanding of the effects of aging in the hypothalamus may reveal important aspects of overall organismal aging and may potentially reveal the most crucial protein factors supporting this vital signaling integration. In this study, we examined alterations in protein expression in the hypothalami of young, middle-aged, and old rats. Using novel combinatorial bioinformatics analyses, we were able to gain a better understanding of the proteomic and phenotypic changes that occur during the aging process and have potentially identified the G protein-coupled receptor/cytoskeletal-associated protein GIT2 as a vital integrator and modulator of the normal aging process