Behavioral and Neurophysiological Correlates of Sensorimotor Impairment in Aphasia

Developing a clearer understanding of the basic impairments which underlie the behavioral characteristics of aphasia is essential for informing the development of targeted and effective treatment techniques. Impairments in sensorimotor integration have already been implicated in the repetition deficits common to individuals with aphasia, but much less is known about the extent to which these integrative deficits occur outside of conduction aphasia and how this manifests behaviorally in areas other than speech repetition. The goal of the present study was to examine these issues further by addressing the following aims: 1) To examine the behavioral and neurophysiological correlates of sensorimotor impairment of speech feedback processing in individuals with aphasia using the altered auditory feedback paradigm and 2) To determine if the poor AAF response is associated with impaired self-correction in aphasia. The combination of multiple neuroimaging modalities and behavioral testing will help expand our knowledge of the pervasiveness of this deficit, the brain regions implicated, and the connections between a basic integrative function and the resultant language-level difficulties

Quantitative analysis of the effect of tubulin isotype expression on sensitivity of cancer cell lines to a set of novel colchicine derivatives

<p>Abstract</p> <p>Background</p> <p>A maximum entropy approach is proposed to predict the cytotoxic effects of a panel of colchicine derivatives in several human cancer cell lines. Data was obtained from cytotoxicity assays performed with 21 drug molecules from the same family of colchicine compounds and correlate these results with independent tubulin isoform expression measurements for several cancer cell lines. The maximum entropy method is then used in conjunction with computed relative binding energy values for each of the drug molecules against tubulin isotypes to which these compounds bind with different affinities.</p> <p>Results</p> <p>We have found by using our analysis that <it>αβ</it>I and <it>αβ</it>III tubulin isoforms are the most important isoforms in establishing predictive response of cancer cell sensitivity to colchicine derivatives. However, since <it>αβ</it>I tubulin is widely distributed in the human body, targeting it would lead to severe adverse side effects. Consequently, we have identified tubulin isotype <it>αβ</it>III as the most important molecular target for inhibition of microtubule polymerization and hence cancer cell cytotoxicity. Tubulin isotypes <it>αβ</it>I and <it>αβ</it>II are concluded to be secondary targets.</p> <p>Conclusions</p> <p>The benefit of being able to correlate expression levels of specific tubulin isotypes and the resultant cell death effect is that it will enable us to better understand the origin of drug resistance and hence design optimal structures for the elimination of cancer cells. The conclusion of the study described herein identifies tubulin isotype <it>αβ</it>III as a target for optimized chemotherapy drug design.</p

The hippocampus and entorhinal cortex encode the path and Euclidean distances to goals during navigation

BACKGROUND Despite decades of research on spatial memory, we know surprisingly little about how the brain guides navigation to goals. While some models argue that vectors are represented for navigational guidance, other models postulate that the future path is computed. Although the hippocampal formation has been implicated in processing spatial goal information, it remains unclear whether this region processes path- or vector-related information. RESULTS We report neuroimaging data collected from subjects navigating London's Soho district; these data reveal that both the path distance and the Euclidean distance to the goal are encoded by the medial temporal lobe during navigation. While activity in the posterior hippocampus was sensitive to the distance along the path, activity in the entorhinal cortex was correlated with the Euclidean distance component of a vector to the goal. During travel periods, posterior hippocampal activity increased as the path to the goal became longer, but at decision points, activity in this region increased as the path to the goal became closer and more direct. Importantly, sensitivity to the distance was abolished in these brain areas when travel was guided by external cues. CONCLUSIONS The results indicate that the hippocampal formation contains representations of both the Euclidean distance and the path distance to goals during navigation. These findings argue that the hippocampal formation houses a flexible guidance system that changes how it represents distance to the goal depending on the fluctuating demands of navigation

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

Couple Therapy for Military Veterans: Overall Effectiveness and Predictors of Response

Despite the numerous challenges facing U.S. veterans and their relationships, there have been no examinations of the effectiveness of couple therapy for relationship distress provided to veterans. In the present study, 177 couples presenting for couple therapy at two Veteran Administration Medical Centers completed assessments of relationship satisfaction prior to therapy and weekly during therapy. Results revealed that the average couple showed significant gains in relationship satisfaction during treatment (d=0.44 for men; d=0.47 for women); gains were larger for couples beginning therapy in the distressed range (d=0.61 for men; d=0.58 for women) than for couples in the nondistressed range (d=0.19 for men; d=0.22 for women). Rates of premature termination were high, with 19% of couples completing fewer than three sessions and 62% rated as not completing a “full course” of therapy. Benchmarking analyses demonstrated that the average gains were larger than would be expected from natural remission and similar to previous effectiveness trials; however, average gains were smaller than those observed in couple therapy efficacy trials. Relationship, psychological, and demographic characteristics were generally unrelated to the amount of change in therapy after controlling for initial satisfaction. However, African American couples showed significantly larger gains than Caucasian, non-Hispanic couples. Thus, though yielding smaller effects than those shown in efficacy trials, the impact of couple therapy for veterans’ relationship problems appears to generalize across various demographic, psychological, and relationship characteristics. ► This study examined outcomes of behavioral couple therapy in 177 couples. ► Therapy resulted in significant improvement in relationship satisfaction. ► Gains were larger than what would be expected without treatment. ► Gains were smaller than most efficacy trials of behavior couple therapy. ► Gains were larger for more distressed and African-American couples