The science of prevention: A conceptual framework and some directions for a national research program.

A conceptual framework for studying the prevention of human dysfunction is offered. On the basis of recent advances in research on the development of psychological disorders and methods of preventive intervention, generalizations about the relation of risk and protective factors to disorder are put forward, along with a set of principles for what may be identified as the science of prevention. Emerging themes from the study of human devlopment, in general, need to be incorporated in the models for explaining and preventing serious problems of human adaptation. The article concludes with a set of recommendations for a national prevention research agenda. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Activity memory and aging: The role of motor retrieval and strategic processing.

Examined the role of retrieval and encoding mechanisms in the magnitude of age differences in the recall of S-performed tasks (SPTs). 80 older (60–79 yrs old) and 80 younger adults (18–26 yrs old) were tested in 1 of 4 conditions by varying modality at both encoding and retrieval. The role of list organization in reducing age differences in SPT recall was also examined. The results suggested that older adults' SPT recall improves when motor processing is enhanced by list organization. Age differences in recall were reduced for an organized list when motor processing occurred during retrieval or encoding, but age differences in recall of an unorganized list remained under most conditions. Discrepant results in the literature concerning the magnitude of age differences in SPT recall could be due in part to differences in list characteristics, such as organization, that have not been fully explored. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Abortion and mental health: Evaluating the evidence.

The authors evaluated empirical research addressing the relationship between induced abortion and women’s mental health. Two issues were addressed: (a) the relative risks associated with abortion compared with the risks associated with its alternatives and (b) sources of variability in women’s responses following abortion. This article reflects and updates the report of the American Psychological Association Task Force on Mental Health and Abortion (2008). Major methodological problems pervaded most of the research reviewed. The most rigorous studies indicated that within the United States, the relative risk of mental health problems among adult women who have a single, legal, first-trimester abortion of an unwanted pregnancy is no greater than the risk among women who deliver an unwanted pregnancy. Evidence did not support the claim that observed associations between abortion and mental health problems are caused by abortion per se as opposed to other preexisting and co-occurring risk factors. Most adult women who terminate a pregnancy do not experience mental health problems. Some women do, however. It is important that women’s varied experiences of abortion be recognized, validated, and understood. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Human DNA topoisomerase IIbeta binds and cleaves four-way junction DNA in vitro

We have used gel retardation analysis to show that human DNA topoisomerase IIbeta can bind a 40 bp linear duplex containing a single DNA topoisomerase IIbeta cleavage site. Furthermore, we demonstrate for the first time that human DNA topoisomerase IIbeta binds to four-way junction DNA. This supports previous suggestions that topoisomerase II may be targeted to supercoiled DNA through the recognition of DNA cruciforms, helix-helix crossovers and hairpins. DNA topoisomerase IIbeta had a 4-fold higher affinity for the four-way junction than for the linear duplex, as demonstrated by protein titration and competition analysis. Furthermore, the DNA topoisomerase IIbeta:four-way junction complex was significantly more salt stable than the complex with linear DNA. The four-way junction contained potential topoisomerase IIbeta cleavage sites straddling the points of strand exchange, and indeed, topoisomerase IIbeta was able to cleave three of these four predicted sites. This indicates that topoiso-merase IIbeta can bind to the centre of the junction. Topoisomerase II has to bind both the transported and the gated DNA helices prior to strand passage, and it is possible that both helices are provided by the four-way junction in this case. The stable complex of DNA topoisomerase IIbeta with four-way junction DNA may provide an ideal substrate for further studies into the mechanism of substrate recognition and binding by DNA topoisomerase II.     

Profile of fiber types in muscles from wild pigs native to the United States

Histochemical and histological parameters of the longissimus (LD) and semitendinosus (dark and light portions) muscles from wild pigs native to Florida, USA, were investigated. All three fiber types were present in both muscles at varying proportions with typical (red fibers grouped in clumps and surrounded by white fibers) fiber arrangements for domestic porcine muscles (Cassens, 1971), contrary to the findings by Rahelic & Puac (1981), who examined the LD muscle of wild pigs native to Yugoslavia. These authors foud only βR fibers present in the LD muscle. In five of the six pigs in the present study, extremely and abnormally large fibers (giant fibers), possessing βR fiber characteristics, were observed. These giant fibers were found in both the LD and the semitendinosus (dark and light portions) and were not restricted to the periphery of the fasiculi. The presence of these giant fibers suggests some type of muscle myopathy syndrome in these pigs.     

The extraction of ionic conductivities and hopping rates from a.c. conductivity data

Over a wide range of frequencies, the a.c. conductivity of ionic materials shows two regions of frequency-dependent conductivity. These are each characterized by a term K _p ^{1–n n} where K, n are constants, _p is a fundamental frequency identified with the hopping rate and is the measuring frequency. This behaviour is an example of Jonscher's Law of Dielectric Response for ionic conductors. In many cases, the region of low-frequency dispersion approximates to a frequency-independent plateau which may be taken as the d.c. conductivity. In others, a significant low-frequency dispersion is present and cannot be ignored in determining the effective d.c. conductivity. A method for the extraction of d.c. conductivities, hopping rates and for estimating carrier concentration effects is described. Data for three different types of material, single-crystal LiGaO₂, -alumina and Na/Ag -alumina are used to illustrate the method.     

Matrix-assisted laser desorption/ionization-ion mobility separation-mass spectrometry imaging of vinblastine in whole body tissue sections

During early-stage drug development, drug and metabolite distribution studies are carried out in animal tissues using a range of techniques, particularly whole body autoradiography (WBA). While widely employed, WBA has a number of limitations, including the following: expensive synthesis of radiolabeled drugs and analyte specificity and identification. WBA only images the radiolabel. MALDI MSI has been shown previously to be advantageous for imaging the distribution of a range of drugs and metabolites in whole body sections. Ion mobility separation (IMS) adds a further separation step to imaging experiments; demonstrated here is MALDI-IMS-MS whole body imaging of rats dosed at 6 mg/kg i.v. with an anticancer drug, vinblastine and shown is the distribution of the precursor ion m/z 811.4 and several product ions including m/z 793, 751, 733, 719, 691, 649, 524, and 355. The distribution of vinblastine within the ventricles of the brain is also depicted. Clearly demonstrated in these data are the removal of interfering isobaric ions within the images of m/z 811.4 and also of the transition m/z 811-751, resulting in a higher confidence in the imaging data. Within this work, IMS has shown to be advantageous in both MS and MS/MS imaging experiments by separating vinblastine from an endogenous isobaric lipid.     

Thermodynamic analysis of protein stability and ligand binding using a chemical modification- and mass spectrometry-based strategy

Described here is a new technique, termed SPROX (stability of proteins from rates of oxidation), that can be used to measure the thermodynamic stability of proteins and protein-ligand complexes. SPROX utilizes hydrogen peroxide in the presence of increasing concentrations of a chemical denaturant to oxidize proteins. The extent of oxidation at a given oxidation time is determined as a function of the denaturant concentration using either electrospray or matrix-assisted laser desorption/ionization mass spectrometry. Ultimately, the denaturant concentration dependence of the oxidation reaction rate is used to evaluate a folding free energy (DeltaG(f)) and m value (deltaDeltaG(f)/delta[Den]) for the protein's folding/unfolding reaction. Measurements of such SPROX-derived DeltaG(f) and m values on proteins in the presence and absence of ligands can also be used to evaluate protein-ligand affinities (e.g., DeltaDeltaG(f) and Kd values). Presented here are SPROX results obtained on four model protein systems including ubiquitin, ribonuclease A (RNaseA), cyclophilin A (CypA), and bovine carbonic anhydrase II (BCAII). SPROX-derived DeltaG(f) and m values on these proteins are compared to values obtained using more established techniques (e.g., CD spectroscopy and SUPREX). The dissociation constants of several known protein-ligand complexes involving these proteins were also determined using SPROX and compared to previously reported values. The complexes included the CypA-cyclosporin A complex and the BCAII-4-carboxybenzenesulfonamide complex. The accuracy and precision of SPROX-derived thermodynamic parameters for the model proteins and protein-ligand complexes in this study are discussed as well as the caveats of the technique.     

Biocompatible carbohydrate-functionalized stainless steel surfaces: a new method for passivating biomedical implants

A convenient method for passivating and functionalizing stainless steel is described. Several methods of coating stainless steel (SS) samples with silica were investigated and of these methods, a thin (less than 15 nm thick) layer of silica created by atomic layer deposition (ALD) was found to give superior performance in electrochemical testing. These interfaces were then used as a platform for further functionalization with molecules of biological interest. Specifically, the SS samples were functionalized with biologically significant carbohydrates [N-acetyl-D-glucosamine (GlcNAc) and D-galactose (Gal)] that contain trialkoxysilane derivatives as chemical handles for linking to the surface. The presence and biological availability of these moieties on the silica coated SS were confirmed by XPS analysis and an enzyme-linked lectin assay (ELLA) using complementary lectins that specifically recognize the surface-bound carbohydrate. This method has the potential of being adapted to the functionalization of stainless steel biomedical implants with other biologically relevant carbohydrates.