Finding needles in haystacks: Reranking DOT results by using shape complementarity, cluster analysis, and biological information.

We present an evaluation of our results for the first Critical Assessment of PRedicted Interaction (CAPRI). The methods used include the molecular docking program DOT, shape analysis tool FADE, cluster analysis and filtering based on biological data. Good results were obtained for most of the seven CAPRI targets, and for two systems, submissions having the highest number of correctly predicted contacts were produced.

Store-operated Ca2+ entry in first trimester and term human placenta.

We have examined whether store-operated Ca2+ entry, a common pathway for Ca2+ entry in non-excitable tissue, is apparent in the syncytiotrophoblast of both first trimester and term human placenta. Expression of transient receptor potential (TRPC) homologues, a family of channels thought to be involved in store-operated Ca2+ entry, was also studied at the mRNA and protein levels. [Ca2+]i in syncytiotrophoblast of first trimester and term placental villous fragments was measured by microfluorimetry using the Ca2+-sensitive dye fura-2.

Returning nurses to the workforce: developing an online refresher course.

The crisis of a nursing shortage is encouraging unemployed nurses to return to practice. A refresher course is needed before they return safely. Historically, schools of nursing and hospital-based continuing education departments offered refresher courses in the traditional classroom-based environments.

When protocols are not enough. Intuitive decision making by novice nurse practitioners.

The pressing need for health care reform in this century has contributed to an increasing interest in educating health care providers who can deliver cost-effective, high-quality care. Demand for primary care nurse practitioners has risen significantly, and nursing education has responded by increasing the numbers and graduates of nurse practitioner programs. Although this century brings new opportunities for expanded nursing roles, it also presents challenges for nurse practitioners to sustain a holistic perspective while providing quality care.

Identification of a new cryptochrome class. Structure, function, and evolution.

Cryptochrome flavoproteins, which share sequence homology with light-dependent DNA repair photolyases, function as photoreceptors in plants and circadian clock components in animals. Here, we coupled sequencing of an Arabidopsis cryptochrome gene with phylogenetic, structural, and functional analyses to identify a new cryptochrome class (cryptochrome DASH) in bacteria and plants, suggesting that cryptochromes evolved before the divergence of eukaryotes and prokaryotes. The cryptochrome crystallographic structure, reported here for Synechocystis cryptochrome DASH, reveals commonalities with photolyases in DNA binding and redox-dependent function, despite distinct active-site and interaction surface features.

ATP-stimulated Ca(2+)-activated K(+) efflux pathway and differentiation of human placental cytotrophoblast cells.

The aim of this study was to determine whether extracellular ATP ([ATP](o)) stimulated a Ca(2+)-activated K(+) efflux in trophoblast cells that was dependent on extracellular Ca(2+) ([Ca(2+)](o)). Cytotrophoblast cells, isolated from human placenta, were examined following 18 h (relatively undifferentiated) and 66 h (multinucleate cells) of culture. Potassium efflux was measured using (86)Rb as a trace marker.

MDB: the Metalloprotein Database and Browser at The Scripps Research Institute.

The Metalloprotein Database and Browser (MDB; http://metallo.scripps.edu) at The Scripps Research Institute is a web-accessible resource for metalloprotein research.

Managing strategic outsourcing in the healthcare industry.

Hospitals and healthcare systems are facing increased financial difficulties because of the Balanced Budget Act of 1997 and managed care. As a result, healthcare executives face the challenge of reducing costs while maintaining quality patient care. One of the strategic tools healthcare executives use to meet this challenge is outsourcing.

Protein docking using continuum electrostatics and geometric fit.

The computer program DOT quickly finds low-energy docked structures for two proteins by performing a systematic search over six degrees of freedom. A novel feature of DOT is its energy function, which is the sum of both a Poisson-Boltzmann electrostatic energy and a van der Waals energy, each represented as a grid-based correlation function. DOT evaluates the energy of interaction for many orientations of the moving molecule and maintains separate lists scored by either the electrostatic energy, the van der Waals energy or the composite sum of both.

Creating a healing environment: the importance of the service setting in the new consumer-oriented healthcare system.

Over the last ten years, the healthcare industry has recognized that the physical environment is a valuable resource that can and does affect all of its customers. Although most service organizations give some thought to setting, its importance to the service experience has been most thoroughly understood by those who view and treat their customers as guests, that is, the guest service industry. An excellent healing environment will reinforce excellent clinical quality, but an inferior environment can detract from fine clinical care.

Stabilization of bound polycyclic aromatic hydrocarbons by a pi-cation interaction.

Proteins can use aromatic side-chains to stabilize bound cationic ligands through cation-pi interactions. Here, we report the first example of the reciprocal process, termed pi-cation, in which a cationic protein side-chain stabilizes a neutral aromatic ligand. Site-directed mutagenesis revealed that an arginine side-chain located in the deep binding pocket of a monoclonal antibody (4D5) is essential for binding the neutral polynuclear aromatic hydrocarbon benzo[a]pyrene.

Globalization of U.S. health care services: assessment and implementation.

Globalization has become a commonly used term to describe the manner in which organizations in many industries have spread their operations and management to foreign countries. As the trend toward a global economy progresses, more and more industries, including health care, are looking to capitalize on its possible benefits. This article examines globalization in other industries and applies the tools used elsewhere to U.

Cyclic peptide formation catalyzed by an antibody ligase.

Cyclic hexapeptides represent a class of compounds with important, diverse biological activities. We report herein that the antibody 16G3 catalyzes the cyclization of d-Trp-Gly-Pal-Pro-Gly-Phe small middle dotp-nitrophenyl ester (8a) to give c-(d-Trp-Gly-Pal-Pro-Gly-l-Phe) (11a). The antibody does not, however, catalyze either epimerization or hydrolysis.

Definition of the interaction domain for cytochrome c on cytochrome c oxidase. III. Prediction of the docked complex by a complete, systematic search.

The electron transfer complex between bovine cytochrome c oxidase and horse cytochrome c has been predicted with the docking program DOT, which performs a complete, systematic search over all six rotational and translational degrees of freedom. Energies for over 36 billion configurations were calculated, providing a free-energy landscape showing guidance of positively charged cytochrome c to the negative region on the cytochrome c oxidase surface formed by subunit II. In a representative configuration, the solvent-exposed cytochrome c heme edge is within 4 A of the indole ring of subunit II residue Trp(104), indicating a likely electron transfer path.

Convergent and discriminant validity of the CVLT (dementia version). California Verbal Learning Test.

This study investigated the convergent and discriminant validity of the 9-item "dementia version'' of the California Verbal Learning Test (CVLT-9) in a sample of 130 geriatric patients evaluated for memory complaints. Moderate correlations were observed between the CVLT-9 sum of words recalled for trials 1-5 (Trial 1-5 Recall) and Long-Delay Free Recall (LDFR) measures and the immediate and delayed Logical Memory (LM I and LM II) and Visual Reproduction (VR I and VR II) subtests from the Wechsler Memory Scale-Revised (WMS-R). However, the CVLT-9 Trial 1-5 Recall and VR I measures demonstrated significant correlations with a number of additional measures of language and visuospatial ability.

Activin A regulation of gonadotropin-releasing hormone synthesis and release in vitro.

Activin is essential for the regulation of normal mammalian reproductive function at both the pituitary and gonadal levels. However, its central actions in the control of the hypothalamic-pituitary-gonadal axis remain largely unexplored. The present study aims to determine whether activin could regulate the reproductive axis at the level of the hypothalamus, through control of the GnRH neuroendocrine system.

Pax6 is implicated in murine pituitary endocrine function.

Pax6, an evolutionarily conserved transcription factor, is expressed in the murine and zebrafish embryonic pituitary, but its role in pituitary development and endocrine function has not been described. To study the role of Pax6 in vivo, we examined Pax6 mutant mouse (SeyNeu) pituitaries. Mice homozygous for the SeyNeu mutation die at birth; therefore, we examined peptide hormone expression by the differentiated pituitary cell types as well as developmental marker expression in the intermediate and anterior lobes of the embryonic pituitary.

Unraveling the effect of changes in conformation and compactness at the antibody V(L)-V(H) interface upon antigen binding.

We have analyzed conformational changes that occur at the interface between the light (V(L)) and heavy (V(H)) chains in antibody variable fragments upon binding to antigens. We wrote and applied the Tiny Probe program that computes the buried atomic contact surface area of three-dimensional structures to evaluate changes in compactness of the V(L)-V(H) interface between bound and unbound antibodies. We found three categories of these changes, which correlated with the size of the antigen.

Structural basis for amide hydrolysis catalyzed by the 43C9 antibody.

Among catalytic antibodies, the well-characterized antibody 43C9 is unique in its ability to catalyze the difficult, but desirable, reaction of selective amide hydrolysis. The crystallographic structures that we present here for the single-chain variable fragment of the 43C9 antibody, both with and without the bound product p -nitrophenol, strongly support and extend the structural and mechanistic information previously provided by a three-dimensional computational model, together with extensive biochemical, kinetics, and mutagenesis results. The structures reveal an unexpected extended beta-sheet conformation of the third complementarity determining region of the heavy chain, which may be coupled to the novel indole ring orientation of the adjacent Trp H103.

Expression of activin and follistatin in the rat hypothalamus: anatomical association with gonadotropin-releasing hormone neurons and possible role of central activin in the regulation of luteinizing hormone release.

The central role of activin in the regulation of the reproductive axis remains largely unexplored. Evidence suggests that activin may play a role in control-linggonadotropin-releasing hormone (GnRH) release. We assessed potential neuroanatomical associations between activin- and GnRH-neuronal systems via examination of the distribution of activin betaA-subunit and activin binding protein (follistatin) protein and mRNA signals relative to GnRH neurons in the adult rat brain.

Monoclonal antibody-based ELISAs for part-per-billion determination of polycyclic aromatic hydrocarbons: effects of haptens and formats on sensitivity and specificity.

As a first step toward developing sensitive enzyme-linked immunosorbent assays (ELISAs) for multianalyte detection of polycyclic aromatic hydrocarbons (PAHs), haptens with different lengths of carboxylic acid spacers at various positions were derived from naphthalene, fluorene, anthracene, phenanthrene, pyrene, fluoranthene, chrysene, and benzo[a]pyrene (BaP). These haptens were coupled with bovine serum albumin (BSA) to form competitor conjugates. All of these haptens were recognized to different extents by monoclonal antibodies (MAbs) 4D5 and 10C10 originally derived by Gomes and Santella (Chem.

Complex formation between Azotobacter vinelandii ferredoxin I and its physiological electron donor NADPH-ferredoxin reductase.

In Azotobacter vinelandii, deletion of the fdxA gene, which encodes ferredoxin I (FdI), leads to activation of the expression of the fpr gene, which encodes NADPH-ferredoxin reductase (FPR). In order to investigate the relationship of these two proteins further, the interactions of the two purified proteins have been examined. AvFdI forms a specific 1:1 cross-linked complex with AvFPR through ionic interactions formed between the Lys residues of FPR and Asp/Glu residues of FdI.

Finite element modelling of a residual lower-limb in a prosthetic socket: a survey of the development in the first decade.

A review is presented of the existing finite element models developed from 1987 to 1996 for the biomechanics of lower-limb prostheses. Finite element analysis can be a useful tool in investigating the mechanical interaction between the residual limb and its prosthetic socket, and in computer-aided design and computer-aided manufacturing of prosthetic sockets. Various assumptions and simplifications are made in these models to simplify the actual problem with complex geometry, material properties, boundary and interfacial conditions, as well as loading situations.

Clinical investigation of the pressure and shear stress on the trans-tibial stump with a prosthesis.

A system for measuring pressures and bi-axial shear stresses at the body support interfaces has been developed. This system has been used, in five unilateral trans-tibial amputees, to investigate the stresses at multiple points on the residual limb and prosthetic socket interface during standing and walking. The subjects investigated regularly used a patellar-tendon-bearing socket.