A Dynamic Model for the Evolution of Protein Structure.

Domains are folded structures and evolutionary building blocks of protein molecules. Their three-dimensional atomic conformations, which define biological functions, can be coarse-grained into levels of a hierarchy. Here we build global dynamical models for the evolution of domains at fold and fold superfamily (FSF) levels.

Effect of single dose methylphenidate on walking and postural stability under single- and dual-task conditions in older adults--a double-blind randomized control trial.

Background: Methylphenidate (MPH) action may improve executive function and motor function. Effects of MPH on balance function in older adults were investigated.

Methods: A randomized controlled double-blind study examined the effects of a single dose of MPH on gait and postural stability in 30 healthy older adults (mean age = 74.

Delta chemokine (fractalkine)--a novel mediator of pulmonary arterial hypertension in children undergoing cardiac surgery.

Background: Fractalkine (FKN), a unique chemokine associated with pulmonary hypertension, may be involved in the acute stress response that regulates inflammation after cardiopulmonary bypass (CPB) surgery. We characterized FKN levels and correlated them with clinical parameters in children undergoing cardiac surgery involving CPB.

Methods: Twenty-seven consecutive patients, aged 30 days to 11.

Does high serum progesterone level on the day of human chorionic gonadotropin administration affect pregnancy rate after intracytoplasmic sperm injection and embryo transfer?

Objective: The present study was conducted to evaluate the effect of serum progesterone (P) levels on the day of human chorionic gonadotropin (hCG) administration on embryo quality and pregnancy rate in intracytoplasmic sperm injection (ICSI) cycles.

Design And Setting: This was a retrospective analysis conducted in the in vitro fertilization (IVF) unit of a tertiary hospital.

Patients: Two hundred and one patients who underwent a total of 280 IVF treatment cycles allocated to ICSI during routine IVF/embryo transfer treatment.

Epidemiologic, socioeconomic, and clinical factors associated with severity of respiratory syncytial virus infection in previously healthy infants.

We prospectively quantified disease severity associated with epidemiologic and socioeconomic parameters as well as the clinical factors in 195 previously healthy infants with confirmed respiratory syncytial virus (RSV) infection. Infants were enrolled into three subgroups according to disease severity: outpatients (82 patients), inpatients (100 patients), and intensive care unit patients (13 patients). Epidemiologic parameters such as gestational age, birth weight, chronologic age at presentation, and gender as well as socioeconomic factors such as ethnic origin, family history of asthma, exposure to cigarette smoke, number of family members, presence of pets at home, breast-feeding, and day-care attendance were not found to predict the severity of RSV illness in previously healthy infants.

Heat shock protein 60 enhances CD4+ CD25+ regulatory T cell function via innate TLR2 signaling.

CD4+CD25+ Tregs regulate immunity, but little is known about their own regulation. We now report that the human 60-kDa heat shock protein (HSP60) acts as a costimulator of human Tregs, both CD4+CD25int and CD4+CD25hi. Treatment of Tregs with HSP60, or its peptide p277, before anti-CD3 activation significantly enhanced the ability of relatively low concentrations of the Tregs to downregulate CD4+CD25- or CD8+ target T cells, detected as inhibition of target T cell proliferation and IFN-gamma and TNF-alpha secretion.

Hypertonic saline/epinephrine treatment in hospitalized infants with viral bronchiolitis reduces hospitalization stay: 2 years experience.

Background: We recently published preliminary evidence on the effectiveness of hypertonic saline in infants with viral bronchiolitis.

Objective: To further establish the efficacy of nebulized hypertonic saline in these infants.

Methods: In a continuing, second-year randomized, doubleblind controlled trial, an additional 41 infants (age 2.

Aerosol delivery in respiratory syncytial virus bronchiolitis: hood or face mask?

Objectives: To compare the utility of the hood versus the face mask for delivery of inhaled medications to infants hospitalized with viral bronchiolitis.

Study Design: Randomized, double-blinded, controlled trial; 49 hospitalized infants with viral bronchiolitis, age 2.75 +/- 2.

Cytokine induction by the hepatitis B virus capsid in macrophages is facilitated by membrane heparan sulfate and involves TLR2.

The hepatitis B virus (HBV) core Ag (HBcAg) serves as the structural subunit of the highly immunogenic capsid shell. HBcAg harbors a unique arginine-rich C terminus that was implicated in immune responses induced by the capsid. In this study, we examined the capacity of the HBV capsid to induce proinflammatory and regulatory cytokines in human THP-1 macrophages and the possible underlying mechanism.

Heat shock protein 60 activates cytokine-associated negative regulator suppressor of cytokine signaling 3 in T cells: effects on signaling, chemotaxis, and inflammation.

Previously, we reported that treatment of T cells with the 60-kDa heat shock protein (HSP60) inhibits chemotaxis. We now report that treatment of purified human T cells with recombinant human HSP60 or its biologically active peptide p277 up-regulates suppressor of cytokine signaling (SOCS)3 expression via TLR2 and STAT3 activation. SOCS3, in turn, inhibits the downstream effects of stromal cell-derived-1alpha (CXCL12)-CXCR4 interaction in: 1) phosphorylation of ERK1/2, Pyk2, AKT, and myosin L chain, required for cell adhesion and migration; 2) formation of rear-front T cell polarity; and 3) migration into the bone marrow of NOD/SCID mice.

Heat shock protein 60 inhibits Th1-mediated hepatitis model via innate regulation of Th1/Th2 transcription factors and cytokines.

Extracellular heat shock protein 60 (HSP60) has been considered a proinflammatory danger signal. Yet, HSP60 can also down-regulate experimental immune arthritis and diabetes models by specific inhibition of Th1-like responses. We now report that HSP60 in vitro differentially modulates the expression of Th1/Th2 transcription factors in human T cells: HSP60 down-regulates T-bet, NF-kappaB, and NFATp and up-regulates GATA-3, leading to decreased secretion of TNF-alpha and IFN-gamma and enhanced secretion of IL-10.

Association between common Toll-like receptor 4 mutations and severe respiratory syncytial virus disease.

Background: The clinical spectrum of respiratory syncytial virus (RSV) bronchiolitis in previously healthy infants is extremely variable. Thus, it is likely that factors such as genetic heterogeneity contribute to disease severity. Toll-like receptor 4 (TLR4) and CD14 are part of a receptor complex involved in the innate immune response to RSV.

Nebulized 3% hypertonic saline solution treatment in hospitalized infants with viral bronchiolitis.

Objective: To determine the utility of inhaled hypertonic saline solution to treat infants hospitalized with viral bronchiolitis.

Design: Randomized, double-blind, controlled trial. Fifty-two hospitalized infants (mean +/- SD age, 2.

Nebulized 3% hypertonic saline solution treatment in ambulatory children with viral bronchiolitis decreases symptoms.

Objective: To determine the utility of inhaled hypertonic saline solution to treat ambulatory infants with viral bronchiolitis.

Design: Randomized, double-blind, controlled trial. Sixty-five ambulatory infants (mean +/- SD age, 12.