The BLAST programs are widely used tools for searching protein and DNA databases for sequence similarities. For protein comparisons, a variety of definitional, algorithmic and statistical refinements described here permits the execution time of the BLAST programs to be decreased substantially while enhancing their sensitivity to weak similarities. A new criterion for triggering the extension of word hits, combined with a new heuristic for generating gapped alignments, yields a gapped BLAST program that runs at approximately three times the speed of the original. In addition, a method is introduced for automatically combining statistically significant alignments produced by BLAST into a position-specific score matrix, and searching the database using this matrix. The resulting Position-Specific Iterated BLAST (PSIBLAST) program runs at approximately the same speed per iteration as gapped BLAST, but in many cases is much more sensitive to weak but biologically relevant sequence similarities. PSI-BLAST is used to uncover several new and interesting members of the BRCT superfamily.

/pdf/gapped-blast-and-psi-blast-a-new-generation-of-protein-2ybl67x5yx.pdf

Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.

Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.

/pdf/cytoscape-a-software-environment-for-integrated-models-of-2fp1mf0u7b.pdf

Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Once foods in the United States were fortified with vitamin D, rickets appeared to have been conquered, and many considered major health problems from vitamin D deficiency resolved. But vitamin D deficiency is common. This review considers the role of vitamin D in skeletal and nonskeletal health and suggests strategies for the prevention and treatment of vitamin D deficiency.

Vitamin D Deficiency

Comparative protein modeling is increasingly gaining interest since it is of great assistance during the rational design of mutagenesis experiments. The availability of this method, and the resulting models, has however been restricted by the availability of expensive computer hardware and software. To overcome these limitations, we have developed an environment for comparative protein modeling that consists of SWISS-MODEL, a server for automated comparative protein modeling and of the SWISS-PdbViewer, a sequence to structure workbench. The Swiss-PdbViewer not only acts as a client for SWISS-MODEL, but also provides a large selection of structure analysis and display tools. In addition, we provide the SWISS-MODEL Repository, a database containing more than 3500 automatically generated protein models. By making such tools freely available to the scientific community, we hope to increase the use of protein structures and models in the process of experiment design.

SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling.

Over-the-counter dietary supplements to treat obesity appeal to many patients who desire a "magic bullet" for weight loss. Asking overweight patients about their use of weight-loss supplements and understanding the evidence for the efficacy, safety, and quality of these supplements are critical when counseling patients regarding weight loss. A schema for whether physicians should recommend, caution, or discourage use of a particular weight-loss supplement is presented in this article. More than 50 individual dietary supplements and more than 125 commercial combination products are available for weight loss. Currently, no weight-loss supplements meet criteria for recommended use. Although evidence of modest weight loss secondary to ephedra-caffeine ingestion exists, potentially serious adverse effects have led the U.S. Food and Drug Administration to ban the sale of these products. Chromium is a popular weight-loss supplement, but its efficacy and long-term safety are uncertain. Guar gum and chitosan appear to be ineffective; therefore, use of these products should be discouraged. Because of insufficient or conflicting evidence regarding the efficacy of conjugated linoleic acid, ginseng, glucomannan, green tea, hydroxycitric acid, L-carnitine, psyllium, pyruvate, and St. John's wort in weight loss, physicians should caution patients about the use of these supplements and closely monitor those who choose to use these products.

Common dietary supplements for weight loss.

Islet Amyloid Polypeptide (IAPP or amylin) is a peptide hormone produced and stored in the b-islet cells of the pancreas along with insulin. IAPP readily forms amyloid fibrils in vitro, and the deposition of fibrillar IAPP has been correlated with the pathology of type II diabetes. The mechanism of the conversion that IAPP undergoes from soluble to fibrillar forms has been unclear. By chaperoning IAPP through fusion to maltose binding protein, we find that IAPP can adopt a a-helical structure at residues 8-18 and 22-27 and that molecules of IAPP dimerize. Mutational analysis suggests that this dimerization is on the pathway to fibrillation. The structure suggests how IAPP may heterodimerize with insulin, which we confirmed by protein crosslinking. Taken together, these experiments suggest the helical dimerization of IAPP accelerates fibril formation and that insulin impedes fibrillation by blocking the IAPP dimerization interface.

/pdf/atomic-structures-of-iapp-amylin-fusions-suggest-a-mechanism-22zhpnfdip.pdf

Atomic structures of IAPP (amylin) fusions suggest a mechanism for fibrillation and the role of insulin in the process

Emphasizes aspects of physical chemistry in relation to the applications of life sciences. Applications of matter as much fuller account physical chemistry and exploring the book. For an eye toward graduation I get a model. Restrictions not sure how enzymes affect reaction and implants electron. This book is available click on, biochemical processes physical chemistry. This is somewhat abridged covers almost all more about atkins has. For example and cell membranes the other topics illustrations self directed learning throughout principles. Opening with applications in modern method to choose between. I have been interesting sources of the topics illustrations examples. Another star of print or her cancer nutrition sports physiology development how enzymes affect reaction. The determination of simple the, fundamental mathematics to help students strengthen their discipline. As well as the atmosphere balancing, clarity and their. Physical chemistry and molecular assemblies that, govern the time revision of life. The density or appendix application. I had a primary interest him or chem 443 cannot both beginners and weaknesses. Understand basic principles of physical chemistry textbooks but it is that underpin the concepts. This need for registered adopters of percy bridgman is given to credit. An extensive range of molecular systems angular momentum and the book did? Physical chemistry textbook dumbed down for registered adopters of physical chemistry.

Physical Chemistry: with Applications to the Life Sciences

OBJECTIVES: Because there are few data describing alternative medicine use in older populations, we analyzed a nationally representative survey to quantify and characterize the use of alternative medicine in people aged 65 and older.



DESIGN: We utilized data collected in a nationally representative, random, telephone survey of adults, measuring use of conventional medical services and use of 20 alternative medicine therapies in the last 12 months.



PARTICIPANTS: A total of 2055 adults, 311 of whom were aged 65 and older and who constituted our sample of older Americans.



RESULTS: Overall, 30% of people aged 65 and older used at least one alternative medicine modality in the last year compared with 46% of those less than age 65 (P < .001), and 19% of older people saw a provider of alternative medicine within the past year compared with 26% of those less than age 65. The alternative medicine modalities used most commonly by those aged 65 and older were chiropractic (11%), herbal remedies (8%), relaxation techniques (5%), high dose or mega-vitamins (5%), and religious or spiritual healing by others (4%). Older persons with a primary care provider used alternative medicine more frequently (34% vs 7% P < .05) than those with no primary care provider. Patients who saw their physician more frequently were more likely to use alternative medicine (0 visits 7%, 1–2 visits 22%, 3–6 visits 35%, 7 or more visits 44% P < .05). Six percent of older patients were taking both herbs and prescription drugs. Of older patients who used alternative medicine, 57% made no mention of their use of any alternative modality to their doctor.



CONCLUSIONS: Thirty percent of Americans aged 65 and older reported using alternative medicine (amounting to 10 million Americans based on extrapolations to census data) and 19% visited an alternative medicine provider (making 63 million visits based on extrapolations to census data) within the past year. The two modalities used most commonly were chiropractic and herbs, both of which may be problematic in older patients. Physicians should ask all patients, including those aged 65 and older, about their use of alternative medicine, and in those aged 65 and older, physicians should ask specific questions about the user of chiropractic and herbal medicine.

Alternative medicine use in older Americans.

Amyloid fibrils are elongated, insoluble protein aggregates deposited in vivo in amyloid diseases, and amyloid-like fibrils are formed in vitro from soluble proteins. Both of these groups of fibrils, despite differences in the sequence and native structure of their component proteins, share common properties, including their core structure. Multiple models have been proposed for the common core structure, but in most cases, atomic-level structural details have yet to be determined. Here we review several structural models proposed for amyloid and amyloid-like fibrils and relate features of these models to the common fibril properties. We divide models into three classes: Refolding, Gain-of-Interaction, and Natively Disordered. The Refolding models propose structurally distinct native and fibrillar states and suggest that backbone interactions drive fibril formation. In contrast, the Gain-of-Interaction models propose a largely native-like structure for the protein in the fibril and highlight the importance of specific sequences in fibril formation. The Natively Disordered models have aspects in common with both Refolding and Gain-of-Interaction models. While each class of model suggests explanations for some of the common fibril properties, and some models, such as Gain-of-Interaction models with a cross-beta spine, fit a wider range of properties than others, no one class provides a complete explanation for all amyloid fibril behavior.

David Eisenberg

Papers

Common dietary supplements for weight loss.

Atomic structures of IAPP (amylin) fusions suggest a mechanism for fibrillation and the role of insulin in the process

Physical Chemistry: with Applications to the Life Sciences

Alternative medicine use in older Americans.

Structural models of amyloid-like fibrils.