NLRP7 variants in spontaneous abortions with multilocus imprinting disturbances from women with recurrent pregnancy loss

Journal of Assisted Reproduction and Genetics - Comparative analysis of multilocus imprinting disturbances (MLIDs) in miscarriages from women with sporadic (SPL) and recurrent pregnancy loss (RPL)...     

Method for analyzing signaling networks in complex cellular systems

Now that the human genome has been sequenced, the challenge of assigning function to human genes has become acute. Existing approaches using microarrays or proteomics frequently generate very large volumes of data not directly related to biological function, making interpretation difficult. Here, we describe a technique for integrative systems biology in which: (i) primary cells are cultured under biologically meaningful conditions; (ii) a limited number of biologically meaningful readouts are measured; and (iii) the results obtained under several different conditions are combined for analysis. Studies of human endothelial cells overexpressing different signaling molecules under multiple inflammatory conditions show that this system can capture a remarkable range of functions by a relatively small number of simple measurements. In particular, measurement of seven different protein levels by ELISA under four different conditions is capable of reconstructing pathway associations of 25 different proteins representing four known signaling pathways, implicating additional participants in the NF-kappaBorRAS/mitogen-activated protein kinase pathways and defining additional interactions between these pathways.     

The Predictors study: Development and baseline characteristics of the Predictors 3 cohort

Introduction

The Predictors study was designed to predict the length of time to major disease outcomes in Alzheimer's disease (AD) patients. Here, we describe the development of a new, Predictors 3, cohort.

The effects of emotional valence on hemispheric processing of metaphoric word pairs

Recent theories of metaphor comprehension discuss the cognitive substrates involved in processing metaphors. However, the role of valence perception during metaphor comprehension has received little attention. The present study aims to examine the effect of emotional valence on metaphor processing, as well as the interaction between this effect and hemispheric differences. Metaphoric, literal, and meaningless word pairs were presented to 43 participants who performed a semantic judgment task. Results showed that processing of metaphors with negative valence was faster when done in the right hemisphere as compared with the left hemisphere. These findings indicate that emotional valence interacts with cognitive processes of metaphor comprehension. We discuss valence with respect to the class inclusion model and the fine versus coarse semantic coding model of metaphor processing.     

Aging pathways for organophosphate-inhibited human butyrylcholinesterase, including novel pathways for isomalathion, resolved by mass spectrometry.

Some organophosphorus compounds are toxic because they inhibit acetylcholinesterase (AChE) by phosphylation of the active site serine, forming a stable conjugate: Ser-O-P(O)-(Y)-(XR) (where X can be O, N, or S and Y can be methyl, OR, or SR). The inhibited enzyme can undergo an aging process, during which the X-R moiety is dealkylated by breaking either the P-X or the X-R bond depending on the specific compound, leading to a nonreactivatable enzyme. Aging mechanisms have been studied primarily using AChE. However, some recent studies have indicated that organophosphate-inhibited butyrylcholinesterase (BChE) may age through an alternative pathway. Our work utilized matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry to study the aging mechanism of human BChE inhibited by dichlorvos, echothiophate, diisopropylfluorophosphate (DFP), isomalathion, soman, sarin, cyclohexyl sarin, VX, and VR. Inhibited BChE was aged in the presence of H2O18 to allow incorporation of (18)O, if cleavage was at the P-X bond. Tryptic-peptide organophosphate conjugates were identified through peptide mass mapping. Our results showed no aging of VX- and VR-treated BChE at 25 degrees C, pH 7.0. However, BChE inhibited by dichlorvos, echothiophate, DFP, soman, sarin, and cyclohexyl sarin aged exclusively through O-C bond cleavage, i.e., the classical X-R scission pathway. In contrast, isomalathion aged through both X-R and P-X pathways; the main aged product resulted from P-S bond cleavage and a minor product resulted from O-C and/or S-C bond cleavage.