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Cognitive functioning in late life: the impact of moderate alcohol consumption.

PURPOSE: Sex differences in the association between moderate alcohol consumption and cognitive functioning were examined during 4 years. METHODS: Participants were 2716 US older adults 70 years and older (mean age, = 76.02 years) who were free of cognitive impairment from the Second Longitudinal Study of Aging (1994 to 2000). Multiple logistic regression models were used to predict cognitive functioning (adapted Telephone Interview for Cognitive Status) from average daily alcohol intake (no drink, one drink or less daily, and more than one drink daily) during 4 years after controlling for covariates. RESULTS: Sex differences in the association between alcohol consumption and cognitive functioning were found (p < 0.01). Older adults with alcohol consumption of one drink or less per day had a lower odds of low cognitive functioning compared with abstainers for women (adjusted odds ratio [AOR], 0.67; 95% confidence interval [CI], 0.55-0.83), but not men (AOR, 0.96; 95% CI, 0.69-1.34). CONCLUSIONS: For older adults with a level of cognitive functioning within normal ranges, moderate amounts of alcohol, an average of one drink or less daily, was protective for women, but not men. Caution should be used in suggesting moderate alcohol consumption to maintain cognitive functioning because of the risks of consuming alcohol.

Aged↗

Compositional variation in bacterial genes and proteins with potential expression level.

Usage of guanine and cytosine at three codon sites in eubacterial genes vary distinctly with potential expressivity, as predicted by Codon Adaptation Index (CAI). In bacteria with moderate/high GC-content, G(3) follows a biphasic relationship, while C(3) increases with CAI. In AT-rich bacteria, correlation of CAI is negative with G(3), but non-specific with C(3). Correlations of CAI with residues encoded by G-starting codons are positive, while with those by C-starting codons are usually negative/random. Average Size/Complexity Score and aromaticity of gene-products decrease with CAI, confirming general validity of cost-minimization principle in free-living eubacteria. Alcoholicity of bacterial gene-products usually decreases with expressivity.

Amino Acids↗

[Busulfan and cycosporin in bone graft children].

Most drugs exhibit both inter- and intra-individual pharmacokinetic and pharmacodynamic variability. This variability explains the different responses observed in patients exposed to standard doses and must be taken into consideration when the therapeutic window is narrow. Population pharmacokinetics provides mean (or median) values of pharmacokinetic parameters as well as the distribution pattern and the statistical relationship with covariables in a group of individuals presenting common characteristics. Among the different methods developed for population pharmacokinetics, the data pool method, as well as the two-step and one-step methods (NONMEM and NPEM) are attractive. Population models can then be developed using bayesian logistics to obtain an estimation of the pharmacokinetic parameters of a given patient and predict the most adapted dose in light of the therapeutic target (residual serum concentration, mean concentration.). Busulfan is an alkylizing agent used instead of radiotherapy for pre-graft preparation before bone marrow grafts in children. This compound requires dose monitoring because of its narrow therapeutic window: under-dosing raises the risk of graft rejection; inversely over-dosing can cause potentially fatal complications such as occlusive venous disease. Interindividual variability is characteristic of busulfan kinetics. Several factors can explain part of this variability: age, underlying disease, changes in liver function, drug bioavailability, chronobiology. The short treatments used (most protocols have 16 doses given in four days) require rapid monitoring to propose effective adjustments. In this context, use of bayesian logistics to estimate the patient's pharmokinetic parameters is very useful for correct dosing. This type of monitoring could also be used for other compounds such as cyclosporine, with a narrow therapeutic window.

Bone Marrow Transplantation↗

Computer simulation of after-inhibition in crayfish slowly adapting stretch receptor neuron.

A theoretical model is described which is able to mimic the responses of slowly adapting stretch receptor neurons of crayfish to applied currents. Its principal feature is postspike inhibition, in which each nerve impulses produces a small inhibitory current that decays with a simple exponential time-course that is long compared with normal interspike intervals. The model was simulated with both an analogue and a digital computer. Parameters for particular model neurons were determined both by an analysis of experimental data obtained from adaptation to constant injected currents, and by matching computer output to the data. Parameter values estimated by the two techniques agreed within +/-10%. Model parameters determined from adaptation data successfully predicted the magnitude and time-course of posttetanic hyperpolarization (PTH) in the stretch receptor neuron. In addition, model neurons were able to reproduce posttetanic depression (PTD) as seen in stretch receptor cells.

Animals↗

Fixed behaviours and migration in parasitic flatworms.

This paper considers how fixed behaviours may play a role in post-larval migrations of Entobdella soleae. A general argument is that a shift away from the paradigm of orientation is required to elucidate the mechanisms that parasites use to navigate on the surface of their hosts. Some migrations may rely on fixed behaviours (genetically programmed stereotyped behaviours) that often evolve under predictable environmental conditions with reliable signals. In turbulent and stochastic free-living environments, homeostatic hosts present very predictable topological substrates and physico-chemical characteristics to their parasites. Over the course of evolution on these predictable host substrates, adaptive behaviours in the parasites can become fixed. Examples of endoparasite migration behaviour, particularly that of the common liver fluke, Fasciola hepatica, will be used to develop an approach based on the perceptual worlds of migrating parasites. An important conclusion is that multi-disciplinary approaches, firmly rooted in an understanding of each parasite's natural history, are requisite to successful interpretation of migration behaviours on the host.

Animal Migration↗

Extraocular muscles: basic and clinical aspects of structure and function.

Although extraocular muscle is perhaps the least understood component of the oculomotor system, these muscles represent the most common site of surgical intervention in the treatment of strabismus and other ocular motility disorders. This review synthesizes information derived from both basic and clinical studies in order to develop a better understanding of how these muscles may respond to surgical or pharmacological interventions and in disease states. In addition, a detailed knowledge of the structural and functional properties of extraocular muscle, that would allow some degree of prediction of the adaptive responses of these muscles, is vital as a basis to guide the development of new treatments for eye movement disorders.

Animals↗

Methods for genome-wide analysis of gene expression changes in polyploids.

Polyploidy is an evolutionary innovation, providing extra sets of genetic material for phenotypic variation and adaptation. It is predicted that changes of gene expression by genetic and epigenetic mechanisms are responsible for novel variation in nascent and established polyploids (Liu and Wendel, 2002; Osborn et al., 2003; Pikaard, 2001). Studying gene expression changes in allopolyploids is more complicated than in autopolyploids, because allopolyploids contain more than two sets of genomes originating from divergent, but related, species. Here we describe two methods that are applicable to the genome-wide analysis of gene expression differences resulting from genome duplication in autopolyploids or interactions between homoeologous genomes in allopolyploids. First, we describe an amplified fragment length polymorphism (AFLP)--complementary DNA (cDNA) display method that allows the discrimination of homoeologous loci based on restriction polymorphisms between the progenitors. Second, we describe microarray analyses that can be used to compare gene expression differences between the allopolyploids and respective progenitors using appropriate experimental design and statistical analysis. We demonstrate the utility of these two complementary methods and discuss the pros and cons of using the methods to analyze gene expression changes in autopolyploids and allopolyploids. Furthermore, we describe these methods in general terms to be of wider applicability for comparative gene expression in a variety of evolutionary, genetic, biological, and physiological contexts.

Arabidopsis↗

Caloric restriction leads to regional specialisation of adipocyte function in the rat.

The study analysed the responses of three metabolic parameters in five distinct adipose tissue depots to caloric restriction (4 weeks) in the rat. The aims were to evaluate whether specific adipose tissue depots were recruited for triacylglycerol (TAG) storage and/or mobilisation, and to determine to what extent specific adipose tissue depots exhibited preferences for the source of fatty acid (FA) for TAG storage. Caloric restriction led to a general enhancement of the response of lipoprotein lipase (LPL), FA synthesis and glucose utilisation to a meal. Effects were particularly marked in the parametrial, perirenal and interscapular depots compared with mesenteric and subcutaneous depots. There was no evidence that individual depots selectively expressed a preference for the pathways concerned with the generation of FA for storage (the exogenous (LPL) and the endogenous (synthesis) pathway). However, the temporal sequence of activation of these pathways differed in a manner consistent with a switch from preponderant use of FA produced via de novo synthesis during the very early phase of feeding towards later use of FA derived from circulating TAG. The overall excursions in insulin levels observed in the calorie-restricted rats were comparable to those found in free-feeding rats, but the magnitude and the rapidity of the individual metabolic responses of the adipocyte were augmented. The data are consistent with a general enhancement of insulin sensitivity and responsiveness in adipose tissue of calorie-restricted rats, together with adaptive regional specialisation of adipocyte function. These adaptations would be predicted to facilitate the immediate conservation of dietary nutrients by promoting their storage as the FA or glycerol moieties of adipose tissue TAG and thereby to ensure the regulated release of FA and glycerol from adipose tissue in accordance with the requirement for glucose conservation and/or production.

Adipocytes↗

Biosynthetic studies of substituent homologation in bacteriochlorophylls c and d.

Administration of carbon-13 and carbon-14 labeled glutamate, glycine, and methionine to Chlorobium vibrioforme forma thiosulfatophilum strain D have demonstrated operation of the C5 and C1 metabolic pathways in bacteriochlorophyll c and bacteriochlorophyll d biosynthesis in this organism, with glutamate providing the delta-aminolevulinic acid for macrocycle synthesis and glycine providing the source of the extra homologation at the 4-, 5-, and delta-positions (via S-adenosylmethionine). Further evidence showing that the bacteria appear to adjust the homologue composition of their antenna bacteriochlorophylls in response to varying growth conditions is presented. Timing of these changes within a single culture is consistent with a light adaptation mechanism, which predicts that degree of alkylation is directly proportional to light intensity in the culture; other factors influencing pigment composition during the lifespan of a single culture may also be operating, and these are discussed.

Bacteria↗

Older and younger adults' strategy choices in multiplication: testing predictions of ASCM using the choice/no-choice method.

The choice/no-choice method provides a means of obtaining unbiased estimates of the performance characteristics of strategies. The three experiments in the study illustrate the method's usefulness for testing predictions of alternative models of strategy choice. The experiments focused on 20- and 70-year-olds' choices among mental calculation, use of a calculator, and use of pencil and paper as strategies for solving multidigit multiplication problems. As predicted by the Adaptive Strategy Choice Model (ASCM), (a) differences in the speed and accuracy yielded by the strategies were the strongest predictors of the frequency with which each strategy was chosen on a given problem; (b) features of problems exerted an additional independent influence; and (c) having a choice resulted in better performance than not having one. These results held true for both older and younger adults. Potential extensions of the choice/no-choice method and of ASCM are discussed.

Adolescent↗

Wedded to the job: moderating effects of job involvement on the consequences of job insecurity.

Two hundred eighty-three public-sector employees experiencing a workplace reorganization completed surveys assessing the relationships between job involvement and job insecurity on self-report measures of psychological, behavioral, and physical outcomes. Using C. L. Hulin's (1991) job adaptation theory, differential predictions were made regarding the specific outcomes of job insecurity for high job involvement versus low job involvement employees. Results indicate that employees who were highly invested in their jobs were most adversely affected by job insecurity. Specifically, they reported more negative job attitudes, more health problems, and a higher level of psychological distress than their less involved counterparts when they perceived their jobs to be threatened.

Adult↗

Differential influence of adult and juvenile conspecifics on feeding by weanling rats (Rattus norvegicus): a size-related explanation.

Weanling Sprague Dawley rat pups (Rattus norvegicus) selected between 2 safe palatable diets in concordance with the preferences of either an adult or a juvenile conspecific model (Experiment 1). Nevertheless, weanlings chose to feed more in the vicinity of an adult than in the vicinity of a juvenile, thus fulfilling the prediction of an adaptive feeding strategy (Experiment 2). The weanlings' bias for feeding in the vicinity of an adult was eliminated by increasing the magnitude of pup stimulus to 3 pups (Experiment 3). Thus, weanlings do not possess a specialization rendering them more sensitive to adults than to pups as models for diet selection. By responding to stimulus magnitude, weanlings are more likely to feed with adult conspecifics, choose foods used by them, and derive the benefits correlated with the adults' successful feeding habits.

Animals↗

The transition to siblinghood: a developmental ecological systems perspective and directions for future research.

The birth of a baby sibling is a normative life event for many children. Few studies address this important transition period and changes in the older sibling's adjustment and family relationships following the sibling's birth. The present article presents a developmental ecological systems model for studying changes in family life and the older child's adjustment following the birth of a baby sibling. Simultaneous changes occurring in the family and how these changes are interrelated over time to predict patterns of adaptation after the transition to siblinghood are underscored. Recommendations for designing longitudinal studies that take advantage of recent developments in multilevel modeling are also discussed.

Adaptation, Psychological↗

BasT, a membrane-bound transducer protein for amino acid detection in Halobacterium salinarum.

Halophilic archaea, such as eubacteria, use methyl-accepting chemotaxis proteins (MCPs) to sense their environment. We show here that BasT is a halobacterial transducer protein (Htp) responsible for chemotaxis towards five attractant amino acids. The C-terminus of the protein exhibits the highly conserved regions that are diagnostic for MCPs: the signalling domain for communication with the histidine kinase and the methylation sites that interact with the methylation/demethylation enzymes for adaptation. Hydropathy analysis predicts an enterobacterial-type transducer protein topology for BasT, with an extracellular putative ligand-binding domain flanked by two transmembrane helices and a cytoplasmic domain. BasT-inactivated mutant cells are missing a membrane protein radiolabelled with L-[methyl-3H]-methionine in wild-type cells, confirming that BasT is methylatable and membrane bound. Behavioural analysis of the basT mutant cells by capillary and chemical-in-plug assays demonstrates complete loss of chemotactic responses towards five (leucine, isoleucine, valine, methionine and cysteine) of the six attractant amino acids for Halobacterium salinarum, whereas they still respond to arginine. The volatile methyl group production assays also corroborate these findings and confirm that BasT signalling induces methyl group turnover. Our data identify BasT as the chemotaxis transducer protein for the branched chain amino acids leucine, isoleucine and valine as well as for methionine and cysteine. Thus, BasT and the arginine sensor Car cover the entire spectrum of chemotactic responses towards attractant amino acids in H. salinarum.

Amino Acid Sequence↗

Perspectives in adolescent risk-taking through instrument development.

Understanding the high-risk adolescent's perception of risk taking is essential for health professionals to determine appropriate interventions. The purpose of this study was to examine the psychometric properties of the revised Adolescent Risk-Taking Instrument (ARTI) designed to measure the high-risk adolescent's perception of risk taking. This study also examined the variables that are most predictive of social adaptation and risk taking. An ex post facto design was used to standardize data collection and to assess the psychometric properties of the revised ARTI. The nonprobability sample consisted of 167 adolescents attending school in an urban, health-underserved area. Exploratory factor analysis supported construct validity, and Chronbach's Coefficient Alpha supported internal consistency reliability. The reliability coefficient for the risk taking and social adaptation constructs were .80 and .77, respectively. Current perspectives on adolescent risk taking and implications for the use of the ARTI in clinical practice are addressed.

Adaptation, Psychological↗

Channelrhodopsin-2, a directly light-gated cation-selective membrane channel.

Microbial-type rhodopsins are found in archaea, prokaryotes, and eukaryotes. Some of them represent membrane ion transport proteins such as bacteriorhodopsin, a light-driven proton pump, or channelrhodopsin-1 (ChR1), a recently identified light-gated proton channel from the green alga Chlamydomonas reinhardtii. ChR1 and ChR2, a related microbial-type rhodopsin from C. reinhardtii, were shown to be involved in generation of photocurrents of this green alga. We demonstrate by functional expression, both in oocytes of Xenopus laevis and mammalian cells, that ChR2 is a directly light-switched cation-selective ion channel. This channel opens rapidly after absorption of a photon to generate a large permeability for monovalent and divalent cations. ChR2 desensitizes in continuous light to a smaller steady-state conductance. Recovery from desensitization is accelerated by extracellular H+ and negative membrane potential, whereas closing of the ChR2 ion channel is decelerated by intracellular H+. ChR2 is expressed mainly in C. reinhardtii under low-light conditions, suggesting involvement in photoreception in dark-adapted cells. The predicted seven-transmembrane alpha helices of ChR2 are characteristic for G protein-coupled receptors but reflect a different motif for a cation-selective ion channel. Finally, we demonstrate that ChR2 may be used to depolarize small or large cells, simply by illumination.

Algal Proteins↗

Identification of a key determinant of hepatitis C virus cell culture adaptation in domain II of NS3 helicase.

Efficient replication of hepatitis C virus (HCV) replicons in cell culture is associated with specific sequences not generally observed in vivo. These cell culture adaptive mutations dramatically increase the frequency with which replication is established in vitro. However, replicons derived from HCV isolates that have been shown to replicate in chimpanzees do not replicate in cell culture even when these adaptive mutations are introduced. To better understand this apparent paradox, we performed a gain-of-function screen to identify sequences that could confer cell culture replication competence to replicons derived from chimpanzee infectious HCV isolates. We found that residue 470 in domain II of the NS3 helicase is a critical determinant in cell culture adaptation. Substitutions in residue 470 when combined with the NS5A-S232I adaptive mutation are both necessary and sufficient to confer cell culture replication to otherwise inactive replicons, including those derived from genotype 1b HCV-BK and genotype 1a HCV-H77 isolates. The specific substitution at residue 470 required for replication is context-dependent, with R470M and P470L being optimal for the activity of HCV-BK and HCV-H77 replicons, respectively. Together these data indicate that mutations in the NS3 helicase domain II act in concert with previously identified adaptive mutations and predict that introduction of compatible residues at these positions can confer cell culture replication activity to diverse HCV isolates.

Cells, Cultured↗

The effectiveness of anchor characteristics on perceptual discrimination.

Four experiments using stimuli which varied in size or texture investigated whether shifts in discrimination occurred when anchors and series stimuli were integral or nonintegral A total of 120 male and female college students judged series stimuli with respect to size. Anchors differed from the series stimuli in size or texture. The participants always observed the anchors visually. The E presented series stimuli either to the visual (intramodal) or haptic (crossmodal) sense. Analysis of variance revealed significant shifts in perceptual judgment for anchors presented both intra- and crossmodally but only when anchors and series stimuli dimensions were integral. Adaptation-level theory predicted significant shifts in judgment and properties associated with the dimensional structure of stimuli accounted for the limits of anchor effectiveness.

Discrimination Learning↗