Identification of Recurrent Mutations in the microRNA-Binding Sites of B-Cell Lymphoma-Associated Genes in Follicular Lymphoma

Follicular lymphoma (FL) is a common indolent B-cell lymphoma that can transform into the more aggressive transformed FL (tFL). However, the molecular process driving this transformation is uncertain. In this work, we aimed to identify microRNA (miRNA)-binding sites recurrently mutated in follicular lymphoma patients, as well as in transformed FL patients. Using whole-genome sequencing data from FL tumors, we discovered 544 mutations located in bioinformatically predicted microRNA-binding sites. We then studied these specific regions using targeted sequencing in a cohort of 55 FL patients, found 16 recurrent mutations, and identified a further 69 variants. After filtering for QC, we identified 21 genes with mutated miRNA-binding sites that were also enriched for B-cell-associated genes by Gene Ontology. Over 40% of mutations identified in these genes were present exclusively in tFL patients. We validated the predicted miRNA-binding sites of five of the genes by luciferase assay and demonstrated that the identified mutations in BCL2 and EZH2 genes impaired the binding efficiency of miR-5008 and miR-144 and regulated the endogenous levels of messenger RNA (mRNA).     

Exercise-induced asthma and the asthmatic athlete

Almost all asthmatics involved in moderate to heavy exercise will experience exercise-induced asthma (EIA). Up to 14% of athletes exhibit EIA, symptoms of which include dyspnea, coughing, chest tightness and wheezing. Education, warm-up exercises and pre-treatment with the appropriate medications can enable an athlete to excel and even win a gold medal in the 1996 Olympic games.     

Reactivation of a visual discrimination in early infancy.

16 78–92 day old infants learned to produce movement in 2 successively presented overhead crib mobiles by footkicking in a conjugate reinforcement paradigm. The mobiles differed in both color and pattern displays on the suspended components. Following acquisition, a discrimination was introduced whereby responding was reinforced in the presence of one mobile (the positive stimulus; S+) but not in the presence of the other (the negative stimulus; S–). During a cued-recall retention test administered 21 days after the completion of discrimination training, Ss evidenced no retention of either initial or discrimination training. Nevertheless, a brief reactivation treatment with S+ 24 hrs prior to the long-term retention test alleviated forgetting and restored the S+/S– discrimination. Reactivation with S– was no more effective than no reactivation treatment at all. Results confirm the efficacy of reminder procedures with young infants and demonstrate the specificity with which the reminder alleviates forgetting. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of Fertilization and Fungal and Insect Attack on Systemic Protein Defenses of Austrian Pine

Despite their economic and ecological importance, defense responses of conifers to pests are little understood. In a 3-year experiment, we monitored systemic fungal (Diplodia pinea)- and insect (Neodiprion sertifer)-induced defense protein activities and total soluble proteins in needles and phloem of Austrian pine (Pinus nigra) across a soil fertility gradient. In both years, total soluble protein content of foliage and phloem declined with increasing fertility across induction treatments, while defensive protein activities generally increased with increasing fertility. In 2005, total soluble protein content in branch phloem was increased by fungal inoculation of the stem. Peroxidase activity was suppressed in needles by insect defoliation in 2006, while polyphenol oxidase activity was systemically induced in branch phloem by insect attack in 2005. Trypsin inhibitor activities in phloem did not respond to any induction or fertility treatment. Nutritive quality of Austrian pine tissue declined with increasing fertility, while several protein-based defenses simultaneously increased.     

Reliability-based condition assessment of deteriorating concrete bridges considering load redistribution

A wide variety of models have been proposed for estimating the reliability of highway bridges. For reinforced concrete bridges subjected to environmental attack, time-variant reliability methods have to be used. In this study, the condition of reinforced concrete girder bridges is assessed using a time-variant system reliability approach in which both load and resistance are time-variant quantities. Several system models are considered, including failure of any girder (series system) and failure of a specified number of adjacent girders (series-parallel system). Adaptive importance sampling is used to determine the cumulative-time system failure probability. An existing reinforced concrete T-beam bridge located near Pueblo, Colorado, is investigated. The influence of resistance degradation and post-failure load redistribution is included. A comparison of reliability estimates for several system models is given, including the influence of correlation among initial girder strengths. The results can be used as a guide for the selection of system models for bridge reliability analysis, identification of critical girders in a bridge system, and for the development of optimal reliability-based maintenance strategies for reinforced concrete highway bridges.     

Survey and Evaluation of Damaged Concrete Bridges

It is well known that the U.S. bridge inventory stands in need of repair. For a rational allocation of U.S. investment resources to bridge maintenance, life cycle cost and probabilistic methods must be used. This requires a quantitative estimate of the remaining strength over the intended lifespan for a given bridge. Although nondestructive evaluation methods are becoming established for bridge inspection purposes, specific recommendations for the application of these methods for individual bridges do not exist. This study focuses on reported damage and damage modeling for concrete bridges, with particular attention to Colorado bridges. A survey on degradation mechanisms is briefly presented. Bridge damage is reviewed for a variety of concrete bridges based on information in the literature and from field studies performed by the Colorado Department of Transportation. A catalog of damages and examples that illustrate the variety and severity of damage in these bridges are presented. For the bridges considered in the survey, the most common source of damage is water leaking through deck joints. A method for predicting strength loss is applied to a typical bridge in Colorado. It is shown that corrosion initiation occurs more quickly and normalized strength loss is much greater for shear than for flexure. It is also shown that many reinforced concrete bridges under corrosion attack may be more vulnerable to shear than to bending failure. The results can be used to identify critical elements for inspection and repair, and to assist in the development of rational maintenance planning strategies for concrete bridges.     

ABAM, a model for bioaccumulation of POPs in birds: validation for adult herring gulls and their eggs in Lake Ontario

An Avian BioAccumulation Model (ABAM) of persistent organic pollutant (POP) uptake and elimination in adult life-stage of birds was validated by simulation of concentrations of DDE, dieldrin, mirex, and HCB in herring gull eggs in Lake Ontario for the years 1985, 1990, and 1992. These chemicals represented a range of whole-body half-lives of 82-265 days in the gull. Dietary intake of POPs by a female gull was simulated by a dynamic bioenergetics model which included dependence on temperature, photoperiod, egg production, and feeding chicks. Concentrations in the two main prey fish of the gull in Lake Ontario were used for POP exposure. Clearance from the female was based on a two compartment toxicokinetic model. Egg concentrations were estimated from egg/whole body female concentration ratios. Simulated concentrations were compared to measured concentrations in gull eggs from 4 different colonies in the northern part of Lake Ontario. Simulations using a diet of 81% fish and 19% uncontaminated food resulted in the best fit with least variance among predicted and measured data. The mean ratio of predicted to measured concentrations in eggs was 1.0 +/- 0.27 among chemicals, years, and colonies for this exposure scenario. This result was in excellent agreement with field assessments of herring gull diet composition in Lake Ontario of 80-82% fish. The ability to perform accurate a priorisimulations for the range of test conditions employed in the validation constituted a rigorous test of the soundness of the model's structure and parameterization. With species-specific adjustments, ABAM can be regarded as a general model for lipophilic POPs bioaccumulation in birds.