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.

The crystal structure is described of ribulose 1,5-bisphosphate carboxylase/oxygenase in a new crystal form. This new form (form V) was obtained from a previously known crystal form (form III) through a solid-state phase transition. The solid-state phase transition was brought about by transferring the crystal from a high-salt low-pH mother liquor to a low-salt high-pH synthetic mother liquor. The interplay of electrostatic repulsion and osmotic pressure induced a unit-cell shrinkage of 24 A along the c axis and expansion of 4 A along the a and b axes. The space group also changed from I422 to I4. The new crystal form was shown to be more resistant to X-ray radiation damage, which suggests the effect of crystal stabilization by non-penetrating molecules. The structure of ribulose 1,5-bisphosphate carboxylase/oxygenase in the new crystal form is compared with that of the old crystal form.

Solid-state phase transition in the crystal structure of ribulose 1,5-bisphosphate carboxylase/oxygenase

The reported activity of a photoelectrode reflects all kinds of reactive sites, good or bad. To understand localized behavior, such as catalytic sites or recombination centers, methods for mapping the anisotropic surface photoreactivity are constantly sought. The layered crystal structure of tungsten diselenide, a small bandgap semiconductor of great importance to solar fuels research, makes it especially prone to step-edge defects. Such steps are detrimental to photoelectrochemical performance. The first direct mapping of the photoreactivity of pdoped WSe2 single crystals in solution by using scanning electrochemical microscopy under illumination (photo-SECM) is presented herein. This nondestructive method reveals the anisotropic reactivity of step edges of p-WSe2 photocathodes, which serve as sites for both dark oxidation and lowered photoreduction in the dark and under illumination.

Imaging the Anisotropic Reactivity of a Tungsten Diselenide Photocathode

/pdf/challenges-of-evaluating-homeopathic-treatment-of-acute-4ljo3e9kjn.pdf

Challenges of Evaluating Homeopathic Treatment of Acute Otitis Media

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/pro.5560011101

John Edsall and Protein Science.

Deposits of amyloid fibrils of alpha synuclein are the histological hallmarks of Parkinsons disease, multiple system atrophy, and dementia with Lewy bodies. Although most cases of these diseases are sporadic, autosomal dominant hereditary mutations have been linked to Parkinsons disease and dementia with Lewy bodies. Seeing the changes to the structure of amyloid fibrils bearing these mutations may help to understand these diseases. To this end, we determined the cryoEM structures of alpha synuclein fibrils containing the H50Q hereditary mutation. We find that the H50Q mutation results in two new polymorphs of alpha synuclein, which we term Narrow and Wide Fibrils. Both polymorphs recapitulate the conserved kernel formed by residues 50 to 77 observed in wild type structures; however, the Narrow and Wide Fibrils reveal that H50Q disrupts a key interaction between H50 and E57 on the opposing protofilament, abolishing the extensive protofilament interface formed by preNAC residues in the wild type rod structure. Instead, the Narrow Fibril is formed from a single protofilament and the two protofilaments of the Wide protofilament are held together by only a pair of atoms, the C gamma atoms from the two threonine 59 sidechains. Further, we find that H50Q forms an intramolecular hydrogen bond with K45 leading to the formation of a novel beta arch formed by residues 36 to 46 that features an extensive hydrogen bond network between Y39, T44, and E46. The structures of the H50Q polymorphs help to rationalize the faster aggregation kinetics, higher seeding capacity in biosensor cells, and greater cytotoxicity we observe for H50Q compared to wild type alpha synuclein.

/pdf/cryo-em-structures-of-alpha-synuclein-fibrils-with-the-h50q-25m9xbf78x.pdf

David Eisenberg

Papers

Solid-state phase transition in the crystal structure of ribulose 1,5-bisphosphate carboxylase/oxygenase

Imaging the Anisotropic Reactivity of a Tungsten Diselenide Photocathode

Challenges of Evaluating Homeopathic Treatment of Acute Otitis Media

John Edsall and Protein Science.

Cryo-EM structures of alpha-synuclein fibrils with the H50Q hereditary mutation reveal new polymorphs