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.

F orty-two (42) percent of Americans use some form of alternative medicine, spending 21.2 billion dollars annually,1 and one of the most commonly sought alternative and complementary medicine (ACM) therapies is therapeutic massage, which was used by an estimated 11 percent of the U.S. adult population in 1998. In that year, adults made an estimated 114 million office visits to receive massage treatments.2 Massage has been used as a therapeutic intervention for a variety of illnesses for thousands of years. The Asian roots of massage go back a t lea s t to 1000 BC and so do the or ig in s o f Ayurvedic medicine. Descriptions of massage appear in the ancient medical texts of India, China, Japan, and Tibet. The European roots of massage can be traced back to the seventh century BC. Massage was associated with the cures offered at the temples of Aesculepius and was described in the writings of Hippocrates. Massage has been used to promote relaxation and relieve pain and has been suggested as a useful adjunctive treatment for symptom control for patients at the end of life. Pain is one of the most common symptoms experienced by dying patients. More than 40 percent of patients’ families reported that patients experienced severe pain in the last 3 days of life.3 Others have reported that 60 percent of patients who have cancer have pain.4,5 In many cases (42 percent), pain was inadequately treated in patients with cancer.6 Nearly 80 percent of hospitalized patients have reported pain, while less than half had any mention of pain noted in progress notes by their doctors.7 Even in palliative medicine and in hospice settings, 64–88 percent of patients had inadequately relieved pain, and the most severe symptoms occurred 2 days prior to death.8 During the last 7 days of life, narcotic usage increased significantly. Although symptoms of pain and nausea were reduced, drowsiness worsened substantially and resulted in worse symptom distress scores. Between 15 and 20 percent of patients needed treatment for pain, requiring complete sedation to obtain relief.9 Caregivers often experience symptoms of anxiety and sadness near the end of a patient’s life. Grief phenomena have been welldescribed. Compared to their experience 6 months following death, feelings of sadness are most intrusive in the 6 weeks following the patient’s death as are symptoms such as tearfulness, depression, and anxiety.10 Physical symptoms, such as pain, are most prominent at 6 weeks as well. Small studies have suggested that interventions that provide support to caregivers can improve their satisfaction with care as well as decreasing their physical and emotional stress.11 Only a few studies on the use of massage at the end of life have been reported. In a small study of massage given to patients in a hospice, investigators reported that slow-stroke back massage resulted in changes in vital signs, suggesting improved relaxation.12 Other studies have indicated that massage may be useful in managing cancer pain.13,14 Studies on other populations have suggested a number of potential benefits of massage that are relevant to patients with metastatic cancer. For example, massage has been shown to promote relaxation, reduce anxiety and depression, and improve sleep patterns.15–18 In addition, other studies have indicated that massage may reduce patients’ experience of pain ,13 ,14 ,19–22 ease breathing,23 faci l i tate weight gain,24–26 and increase alertness.27 Finally, data indicate that giving as well as receiving massage may reduce anxiety and depression,28 suggesting that caregivers may benefit from providing massage to patients. In this pilot study, we provided daily massage to hospitalized patients with metastatic or end stage lung or gastrointestinal (GI) cancer. Hospital admissions were screened daily to identify eligible patients. Patients received daily therapeutic massage and family caregivers were also instructed in the use of massage during hospitalization. Data were collected from massage therapists’ detailed documentation and from patients’ daily questionnaires about their experiences with the massage therapy. We also collected data from medical records via chart reviews and interviews with patients’ nurses and physicians.

Therapeutic Massage Intervention for Hospitalized Patients with Cancer: A Pilot Study

A crystal form of ribulose-1,5-bisphosphate carboxylase/oxygenase from Nicotiana tabacum in the activated state.

Sequences and topology Deriving biological knowledge from genomic sequences

http://journals.iucr.org/b/issues/1969/02/00/a06639/a06639.pdf

David Eisenberg

Papers

Therapeutic Massage Intervention for Hospitalized Patients with Cancer: A Pilot Study

A crystal form of ribulose-1,5-bisphosphate carboxylase/oxygenase from Nicotiana tabacum in the activated state.

Sequences and topology Deriving biological knowledge from genomic sequences

Refinement of protein phases with the Karle–Hauptman tangent formula

New crystal forms of glutamine synthetase and implications for the molecular structure.