Structure and energetics of encapsidated DNA in bacteriophage HK97 studied by scanning calorimetry and cryo-electron microscopy.

Encapsidation of duplex DNA by bacteriophages represents an extreme case of genome condensation, reaching near-crystalline concentrations of DNA. The HK97 system is well suited to study this phenomenon in view of the detailed knowledge of its capsid structure. To characterize the interactions involved, we combined calorimetry with cryo-electron microscopy and native gel electrophoresis.

International Society for Medical Publication Professionals (ISMPP) position statement: the role of the professional medical writer.

The International Society for Medical Publication Professionals (ISMPP) is an independent, nonprofit professional association with members from the pharmaceutical, medical device, and biotechnology industries; publication planning and medical communications companies; academia; and medical journal staffs, including editors and publishers. ISMPP's mission is to support the educational needs of medical publication professionals by providing a forum to facilitate awareness and development of best practices in publication planning and implementation, and fostering consensus policies related to medical publishing. This position statement reflects our concern about the current climate of mistrust regarding the use of professional medical writers in the preparation of manuscripts.

A thermally induced phase transition in a viral capsid transforms the hexamers, leaving the pentamers unchanged.

Scanning calorimetry combined with cryo-electron microscopy affords a powerful approach to investigating hierarchical interactions in multi-protein complexes. Calorimetry can detect the temperatures at which certain interactions are disrupted and cryo-EM can reveal the accompanying structural changes. The procapsid of bacteriophage HK97 (Prohead I) is a 450A-diameter shell composed of 60 hexamers and 12 pentamers of gp5, organized with icosahedral symmetry.

A free energy cascade with locks drives assembly and maturation of bacteriophage HK97 capsid.

We investigated the thermodynamic basis of HK97 assembly by scanning calorimetry and cryo-electron microscopy. This pathway involves self-assembly of hexamers and pentamers of the precursor capsid protein gp5 into procapsids; proteolysis of their N-terminal Delta-domains; expansion, a major conformational change; and covalent crosslinking. The thermal denaturation parameters convey the changes in stability at successive steps in assembly, and afford estimates of the corresponding changes in free energy.

How useful are measures of BMD and bone turnover?

Measurements of bone mineral density (BMD) and biochemical markers of bone turnover are useful in the diagnosis and management of osteoporosis, as well as in research relating to the pathogenesis and treatment of the disease. Recent challenges to the utility of these measures have resulted in some confusion among both researchers and clinicians. BMD accounts for the great majority of bone strength and is the current gold standard for the diagnosis of osteoporosis, as well as for prediction of fracture risk.

Effect of alendronate on the age-specific incidence of symptomatic osteoporotic fractures.

Unlabelled: Analyses of data from 3658 postmenopausal women with osteoporosis enrolled in the Fracture Intervention Trial showed that alendronate is effective in reducing the risk of symptomatic osteoporotic fractures across a spectrum of ages.

Introduction: Most osteoporosis studies examine the relative risk of fracture based on the entire duration of treatment. Because older patients tend to be at higher risk for osteoporosis-related fractures, this analysis examined the effect of alendronate treatment on the relative risk of fracture in terms of the age that patients attained during the study.

A risk assessment tool (OsteoRisk) for identifying Latin American women with osteoporosis.

Objective: To develop a simple and easy-to-use tool for identifying osteoporotic women (femoral neck bone mineral density [BMD] T-scores
Design: Retrospective study involving review of medical records.

Crosslinking renders bacteriophage HK97 capsid maturation irreversible and effects an essential stabilization.

In HK97 capsid maturation, structural change ('expansion') is accompanied by formation of covalent crosslinks, connecting residue K169 in the 'E-loop' of each subunit with N356 on another subunit. We show by complementation experiments with the K169Y mutant, which cannot crosslink, that crosslinking is an essential function. The precursor Prohead-II passes through three expansion intermediate (EI) states en route to the end state, Head-II.

Development of a clinical assessment tool in identifying Asian men with low bone mineral density and comparison of its usefulness to quantitative bone ultrasound.

Osteoporosis in men is a largely neglected condition in Asia (and elsewhere), despite the fact that one-third of hip fractures occur in men. Moreover, access to bone mineral density (BMD) measurements is limited in many areas of Asia, and inexpensive methods of targeting high risk patients for BMD measurements would be valuable. We have developed a simple clinical assessment tool to identify high risk Asian men for BMD measurements.

Changes in bone density and turnover after alendronate or estrogen withdrawal.

Objective: To compare bone mineral density (BMD) and bone turnover changes after therapy withdrawal in postmenopausal women treated with alendronate or estrogen-progestin.

Design: In this randomized, blinded, multinational, placebo-controlled trial, 1,609 healthy postmenopausal women ages 45 to 59 years were assigned to receive alendronate, placebo, or open-label estrogen-progestin (conjugated equine estrogens plus medroxyprogesterone acetate or a cyclic regimen of 17 beta-estradiol, norethisterone acetate and estradiol). Of the original women, one third after year 2 and one third after year 4 were switched from alendronate to placebo, while remaining blinded to treatment assignment.

Prevention of postmenopausal bone loss: six-year results from the Early Postmenopausal Intervention Cohort Study.

We report the effect of continuous treatment with alendronate for 6 yr vs. placebo in the Early Postmenopausal Intervention Cohort study. A total of 1609 healthy, early postmenopausal women were recruited; we describe results for the 585 women who received continuous placebo or alendronate (2.

The carboxy-terminal portion of TnsC activates the Tn7 transposase through a specific interaction with TnsA.

Tn7 transposition requires the assembly of a nucleoprotein complex containing four self-encoded proteins, transposon ends, and target DNA. Within this complex, TnsC, the molecular switch that regulates transposition, and TnsA, one part of the transposase, interact directly. Here, we demonstrate that residues 504-555 of TnsC are responsible for TnsA/TnsC interaction.

The N-terminal prion domain of Ure2p converts from an unfolded to a thermally resistant conformation upon filament formation.

According to the "amyloid backbone" model of Ure2p prionogenesis, the N-terminal domain of Ure2p polymerizes to form an amyloid filament backbone surrounded by the C-terminal domains. The latter domains retain their native glutathione-S-transferase (GST)-like fold but are sterically inactivated from their regulatory role in nitrogen catabolism. We have tested this model by differential scanning calorimetry of soluble and filamentous Ure2p and of soluble C-terminal domains, combined with electron microscopy.

Korean experience with the OSTA risk index for osteoporosis: a validation study.

The Osteoporosis Self-assessment Tool for Asians (OSTA) was developed to help physicians focus their efforts on patients at increased risk, and encourage appropriate use of bone mineral density (BMD) measurements. Previously, OSTA performed well in a sample of women from eight countries in Asia, and in a validation group of Japanese women. In this study, we evaluate the performance of OSTA using a sample of 1101 postmenopausal women from a clinic in Korea who had femoral neck BMD measurements by dual-energy X-ray absorptiometry (DXA).

Biochemical markers for prediction of 4-year response in bone mass during bisphosphonate treatment for prevention of postmenopausal osteoporosis.

Short-term changes in biochemical markers of bone turnover (bone markers) have been suggested as predictors of long-term response in bone mass during antiresorptive treatment. In the Danish cohort (n = 306) of the Early Postmenopausal Intervention Cohort (EPIC) Study (n = 1609) of oral alendronate (ALN) for prevention of postmenopausal osteoporosis, bone markers (urine C-telopeptides of type I collagen (uCTX), urine N-telopeptide cross-links of type I collagen (uNTX), serum total osteocalcin measured by ELISA [total OC (ELISA)], and serum total osteocalcin measured by RIA [total OC (RIA)]) were measured at 6-month intervals. The correlation between 6-month change in uCTX and 4-year change in spine and hip bone mineral density (BMD) was r = -0.

Comparison of a simple clinical risk index and quantitative bone ultrasound for identifying women at increased risk of osteoporosis.

Osteoporosis is a growing problem in Asia, and early identification of at risk subjects for preventive measures is likely the most cost-effective method for managing this disease in developing countries. Patients with low bone mineral density (BMD) have a high risk of future fracture. However, access to BMD measurements is limited in many areas of Asia, and inexpensive methods of targeting high-risk patients for BMD measurements would be valuable.

Association of body mass index with joint pain among community-dwelling women in Japan.

Background And Aims: To investigate the impact of obesity on joint pain, we examined the association of body mass index (BMI) with joint pain.

Methods: 351 community-dwelling Japanese women aged 40-85 years were asked about joint pain at specific joints, and height and weight were measured. Logistic regression analysis was used to evaluate BMI and other potential predictors of joint pain.

The thermodynamic contribution of the 5-methyl group of thymine in the two- and three-stranded complexes formed by poly(dU) and poly(dT) with poly(dA).

To assess the thermodynamic contribution of the 5-methyl group of thymine, we have studied the two-stranded helical complexes poly(dA).poly(dU) and poly(dA).poly(dT) and the three-stranded complexes--poly(dA).

Appendicular bone mass and knee and hand osteoarthritis in Japanese women: a cross-sectional study.

Background: It has been reported that there is an inverse association between osteoarthritis (OA) and osteoporosis. However, the relationship of bone mass to OA in a Japanese population whose rates of OA are different from Caucasians remains uncertain.

Methods: We studied the association of appendicular bone mineral density (second metacarpal; mBMD) and quantitative bone ultrasound (calcaneus; stiffness index) with knee and hand OA among 567 Japanese community-dwelling women.

Alendronate reduces the risk of multiple symptomatic fractures: results from the fracture intervention trial.

Objectives: To evaluate the effect of alendronate on the occurrence rate of multiple svmptomatic fractures and on the risk of multiple symptomatic fractures (likelihood of having more than one fracture diagnosed because of the symptoms the fractures caused over the study period) among women with osteoporosis.

Design: Primary analysis of data from a randomized, placebo-controlled, double-blind trial.

Setting: Eleven community-based clinical research centers.

Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents.

Some, but not all, antiresorptive agents have been shown to reduce the risk of nonvertebral fractures. Agents that significantly reduced nonvertebral fracture risk also appear to produce larger mean increases in bone mineral density (BMD) and reductions in biochemical markers (BCM) of bone turnover, compared with other agents. To examine the extent to which increases in BMD and reductions in BCM during antiresorptive therapy are associated with reductions in risk of nonvertebral fractures, we performed a meta-analysis of all randomized, placebo-controlled trials of antiresorptive agents conducted in postmenopausal women with osteoporosis (i.