Issues relevant to therapy with adoptees.

Addresses issues important to clinicians working with adoptees by reviewing the findings that have been articulated in the literature, and more specifically, by illustrating how these findings may affect therapy with an adoptee. Pertinent areas for adoptees include issues of loss, separation, abandonment, trust, betrayal, rejection, worth, and identity. Additionally, challenges inherent in working with adoptees for individual therapists and the profession at large are also briefly addressed. An object-relations theoretical perspective is used, and 1 case example of an adult female who was abandoned as a 7-mo-old infant and later adopted is followed throughout the article. The author notes that work with adoptees can be hard. Human relationships are fragile, and the existence of an adoptee threatens our most revered bond, that of a mother (or parent) and child. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mutations sensitizing yeast cells to the start inhibitor nalidixic acid

The regulatory step Start in the cell cycle of the budding yeast Saccharomyces cerevisiae is inhibited by nalidixic acid (Nal). To study this inhibition, mutations were identified that alter the sensitivity of yeast cells to Nal. Nal-sensitive mutations were sought because the inhibitory effects of Nal on wild-type cells are only transient, and wild-type cells naturally become refractory to Nal. Three complementation groups of Nal-sensitive mutations were found. Mutations in the first complementation group were shown to reside in the ARO7 gene, encoding chorismate mutase; tyrosine and phenylalanine synthesis was inhibited by Nal in these aro7 mutants, whereas wild-type chorismate mutase was unaffected. These aro7 alleles demonstrate ‘recruitment’, by mutation, of an innately indifferent protein to an inhibitor-sensitive form. The Nal-sensitive aro7 mutant cells were used to show that the resumption of Nal-inhibited nuclear activity and cell proliferation takes place while cytoplasmic Nal persists at concentrations inhibitory for the mutant chorismate mutase. Mutations in the second complementation group, nss2 (Nal-supersensitive), increased intracellular Nal concentrations, and may simply alter the permeability of cells to Nal. The third complementation group was found to be the ERG6 gene, previously suggested to encode the ergosterol biosynthetic enzyme sterol methyltransferase. Mutation or deletion of the ERG6 gene had little effect on the inhibition of Start by Nal, but prevented recovery from this inhibition. Mutation of ERG3, encoding another ergosterol biosynthetic enzyme, also caused Nal sensitivity, suggesting that plasma membrane sterol composition, and plasma membrane function, mediates recovery from Nal-mediated inhibition of Start.     

Electrical measurement of cross-sectional position of particles flowing through a microchannel

The first high-throughput system for the electrical detection of cross-sectional position and velocity of individual particles flowing through a rectangular microchannel is presented. Lateral position (along channel width) and vertical position (along channel height) are measured using two different sets of coplanar electrodes. In particular, the ratio of travel times measured with electrodes generating a current flow transverse or oblique with respect to particle trajectory yields lateral position. The relative prominence and transit time of a bipolar double-Gaussian signal obtained with a suited electrode configuration, respectively, supply vertical position and velocity. The operating principle is presented by means of finite element numerical simulations. The method is experimentally validated by comparing the electrical estimates of position and velocity of polystyrene beads with optical estimates obtained by processing high-speed images. The system is used to observe bead focusing at different particle Reynolds numbers. This system, providing a fully electrical characterization of single-particle motion, represents a powerful tool, e.g. to understand fluid motion at the microscale, in particle separation studies, or to assess the performance of particle focusing devices. Moreover, it can be simultaneously used to perform single-cell impedance spectroscopy, thus achieving an unprecedented multiparamteric characterization.     

Insights into the Role of the Microbiota and of Short-Chain Fatty Acids in Rubinstein–Taybi Syndrome

The short-chain fatty acid butyrate, produced by the gut microbiota, acts as a potent histone deacetylase (HDAC) inhibitor. We assessed possible ameliorative effects of butyrate, relative to other HDAC inhibitors, in in vitro and in vivo models of Rubinstein–Taybi syndrome (RSTS), a severe neurodevelopmental disorder caused by variants in the genes encoding the histone acetyltransferases CBP and p300. In RSTS cell lines, butyrate led to the patient-specific rescue of acetylation defects at subtoxic concentrations. Remarkably, we observed that the commensal gut microbiota composition in a cohort of RSTS patients is significantly depleted in butyrate-producing bacteria compared to healthy siblings. We demonstrate that the effects of butyrate and the differences in microbiota composition are conserved in a Drosophila melanogaster mutant for CBP, enabling future dissection of the gut–host interactions in an in vivo RSTS model. This study sheds light on microbiota composition in a chromatinopathy, paving the way for novel therapeutic interventions.     

Archetypal Analysis

Archetypal analysis represents each individual in a data set as a mixture of individuals of pure type or archetypes. The archetypes themselves are restricted to being mixtures of the individuals in the data set. Archetypes are selected by minimizing the squared error in representing each individual as a mixture of archetypes. The usefulness of archetypal analysis is illustrated on several data sets. Computing the archetypes is a nonlinear least squares problem, which is solved using an alternating minimizing algorithm.     

Electronic structure of GaAs1−xNx alloys

We have performed first-principles total-energy calculations based on pseudopotential and plane-wave method on ordered GaAs_1−xN_x alloys. We have found that the alloy is metallic at x≈0.25, has an indirect gap at 0.10<x<0.35 and a direct gap for the rest of the composition range within LDA. The alloy becomes metallic because the conduction band at R point is lower than the valence band maximum at Γ point. This discrepancy with previous calculations can be explained in terms of band folding and strong order dependence of the electronic structure of GaAs_1−xN_x alloys.