Quantitative Assessment of Affinity Selection Performance by Using DNA-Encoded Chemical Libraries

DNA-encoded chemical libraries are often used for the discovery of ligands against protein targets of interest. These large collections of DNA-barcoded chemical compounds are typically screened by using affinity capture methodologies followed by PCR amplification and DNA sequencing procedures. However, the performance of individual steps in the selection procedures has been scarcely investigated, so far. Herein, the quantitative analysis of selection experiments, by using three ligands with different affinity to carbonic anhydrase IX as model compounds, is described. In the first set of experiments, quantitative PCR (qPCR) procedures are used to evaluate the recovery and selectivity for affinity capture procedures performed on different solid-phase supports, which are commonly used for library screening. In the second step, both qPCR and analysis of DNA sequencing results are used to assess the recovery and selectivity of individual carbonic anhydrase IX ligands in a library, containing 360 000 compounds. Collectively, this study reveals that selection procedures can be efficient for ligands with sub-micromolar dissociation constants to the target protein of interest, but also that selection performance dramatically drops if 10⁴ copies per library member are used as the input.     

Site‐Specific Labeling of MicroRNA Precursors: A Structure–Activity Relationship Study

Functionalized oligoribonucleotides are essential tools in RNA chemical biology. Various synthetic routes have been developed over recent years to conjugate functional groups to oligoribonucleotides. However, the presence of the functional group on the oligoribonucleotide backbone can lead to partial or total loss of biological function. The limited knowledge concerning the positioning of functional groups therefore represents a hurdle for the development of oligoribonucleotide chemical tools. Here we describe a systematic investigation of site‐specific labeling of pre‐miRNAs to identify positions for the incorporation of functional groups, in order not to hinder their processing into active mature miRNAs.     

The effects of social support and education on health care costs after three years

This study reports on the results of a randomized controlled trial that evaluated a caregiver-based intervention program for children with autism in community day-care centers. Thirty-five preschool children with a DSM III-R diagnosis of autism or pervasive developmental disorder were randomized to an experimental or control group. Children in the experimental group were enrolled in day care and their parents and child care workers received a 12-week intervention consisting of lectures and on-site consultations to day-care centers. In addition, supportive work was undertaken with families. Control subjects received day care alone. In the experimental group, there were greater gains in language abilities, significant increases in caregivers' knowledge about autism, greater perception of control on the part of mothers, and greater parent satisfaction. We conclude that this research design demonstrated that the intervention was significantly superior to day care alone.     

Gender and exercise behavior among women and men with osteoarthritis

The purposes of this study were to determine differences between women and men with osteoarthritis in (1) amount and type of exercise behavior; (2) the demographic, psychosocial, health status, and personality correlates of exercise behavior; and (3) the relationship between exercise and health care utilization. Participants were 70 male and 126 female members of a large health maintenance organization who were 60 years of age or older and had osteoarthritis. Results indicated fewer women than men exercised, but among those who exercised, no significant differences in the [amount and type of exercise] behavior were found. Walking was the most frequently reported form of exercise among both women and men. To clarify which variables were related to exercise within each gender, regression analyses were performed separately on the total sample first, and then on women and men separately. In the total sample, age, quality of well-being, and extroversion were significantly related to exercise. Extroversion was significantly related to exercise among men. Helplessness and quality of well-being were significantly related to exercise among women. Exercise was not significantly related to health care service utilization. Results in this study underscore the importance of separating women and men in examination of variables related to exercise behavior.     

An examination of the physical health, health care use, and psychological well-being of spouses of people with fibromyalgia syndrome.

The present study compared the physical and mental health and the health care use of spouses of patients with fibromyalgia syndrome (FS group; n=135) with that of spouses of healthy individuals ( n=153). FS group participants reported lower health and affective states and scored higher on depression, loneliness, and subjective stress than comparison group participants ( p=.017). Husbands in the FS group who reported more illness impact and whose wives reported worse sleep quality and less self-efficacy had more psychological difficulties. No differences were found in health care costs between groups. These findings suggest that chronic illness in a partner may negatively affect an individual's physical and mental health. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

On the computation of hilbert—Poincaré series

We prove a theorem, which provides a formula for the computation of the Poincaré series of a monomial ideal ink[X₁,, X_n], via the computation of the Poincaré series of some monomial ideals ink[X ₁,, X_i,, X_n]. The complexity of our algorithm is optimal for Borel-normed ideals and an implementation in CoCoA strongly confirms its efficiency. An easy extension computes the Poincaré series of graded modules over standard algebras.The paper was partly written while the third author was visiting Queen's University, during the academic year 1989/90. It was partly supported by the Natural Sciences & Engineering Research Council of Canada, Queen's University (Kingston, Canada) and Consiglio Nazionale delle Ricerche