Alternative exon usage in the single CPT1 gene of Drosophila generates functional diversity in the kinetic properties of the enzyme:differential expression of alternatively spliced variants in drosophila tissues

The Drosophila melanogaster genome contains only one CPT1 gene (Jackson, V. N., Cameron, J. M., Zammit, V. A., and Price, N. T. (1999) Biochem. J. 341, 483-489). We have now extended our original observation to all insect genomes that have been sequenced, suggesting that a single CPT1 gene is a universal feature of insect genomes. We hypothesized that insects may be able to generate kinetically distinct variants by alternative splicing of their single CPT1 gene. Analysis of the insect genomes revealed that (a) the single CPT1 gene in each and every insect genome contains two alternative exons and (ii) in all cases, the putative alternative splicing site occurs within a small region corresponding to 21 amino acid residues that are known to be essential for the binding of substrates and of malonyl-CoA in mammalian CPT1A.Weperformed PCR analyses of mRNA from different Drosophila tissues; both of the anticipated splice variants of CPT1mRNAwere found to be expressed in all of the tissues tested (both in larvae and adults), with the expression level for one of the splice variants being significantly different between flight muscle and the fat body of adult Drosophila. Heterologous expression of the full-length cDNAs corresponding to the two putative variants of Drosophila CPT1 in the yeast Pichia pastoris revealed two important differences between the properties of the two variants: (i) their affinity (K 0.5) for one of the substrates, palmitoyl-CoA, differed by 5-fold, and (ii) the sensitivity to inhibition by malonyl-CoA at fixed, higher palmitoyl-CoA concentrations was 2-fold different and associated with different kinetics of inhibition. These data indicate that alternative splicing that specifically affects a structurally crucial region of the protein is an important mechanism through which functional diversity of CPT1 kinetics is generated from the single gene that occurs in insects. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Primary and secondary somatosensory cortex responses to anticipation and pain: a magnetoencephalography study

Several brain regions, including the primary and secondary somatosensory cortices (SI and SII, respectively), are functionally active during the pain experience. Both of these regions are thought to be involved in the sensory-discriminative processing of pain and recent evidence suggests that SI in particular may also be involved in more affective processing. In this study we used MEG to investigate the hypothesis that frequency-specific oscillatory activity may be differentially associated with the sensory and affective components of pain. In eight healthy participants (four male), MEG was recorded during a visceral pain experiment comprising baseline, anticipation, pain and post-pain phases. Pain was delivered via intraluminal oesophageal balloon distension (four stimuli at 1 Hz). Significant bilateral but asymmetrical changes in neural activity occurred in the beta-band within SI and SII. In SI, a continuous increase in neural activity occurred during the anticipation phase (20-30 Hz), which continued during the pain phase but at a lower frequency (10-15 Hz). In SII, oscillatory changes only occurred during the pain phase, predominantly in the 20-30 Hz beta band, and were coincident with the stimulus. These data provide novel evidence of functional diversity within SI, indicating a role in attentional and sensory aspects of pain processing. In SII, oscillatory changes were predominantly stimulus-related, indicating a role in encoding the characteristics of the stimulus. We therefore provide objective evidence of functional heterogeneity within SI and functional segregation between SI and SII, and suggest that the temporal and frequency dynamics within cortical regions may offer valuable insights into pain processing.

Meta-analytic model comparisons of surface- and deep-level relational diversity effects on social integration and individual effectiveness

While diversity might give an organization a competitive advantage, individuals have a tendency to prefer homogenous group settings. Prior research suggests that group members who are dissimilar (vs. similar) to their peers in terms of a given diversity attribute (e.g. demographics, attitudes, values or traits) feel less attached to their work group, experience less satisfying and more conflicted relationships with their colleagues, and consequently are less effective. However, prior empirical findings tend to be weak and inconsistent, and it remains unclear when, how and to what extent such differences affect group members’ social integration (i.e. attachment with their work group, satisfaction and conflicted relationships with their peers) and effectiveness. To address these issues the current study conducted a meta-analysis and integrated the empirical results of 129 studies. For demographic diversity attributes (such as gender, ethnicity, race, nationality, age, functional background, and tenure) the findings support the idea that demographic dissimilarity undermines individual member performance via lower levels of social integration. These negative effects were more pronounced in pseudo teams – i.e. work groups in which group members pursue individual goals, work on individual tasks, and are rewarded for their individual performance. These negative effects were however non-existent in real teams - i.e. work groups in which groups members pursue group goals, work on interdependent tasks, and are rewarded (at least partially) based on their work group’s performance. In contrast, for underlying psychological diversity attributes (such as attitudes, personality, and values), the relationship between dissimilarity and social integration was more negative in real teams than in pseudo teams, which in return translated into even lower individual performance. At the same time however, differences in underlying psychological attributes had an even stronger positive effect on dissimilar group member’s individual performance, when the negative effects of social integration were controlled for. This implies that managers should implement real work groups to overcome the negative effects of group member’s demographic dissimilarity. To harness the positive effects of group members’ dissimilarity on underlying psychological attributes, they need to make sure that dissimilar group members become socially integrated.

Diversity faultlines, shared objectives, and top management team performance

Faultline theory suggests that negative effects of team diversity are better understood by considering the influence of different dimensions of diversity in conjunction, rather than for each dimension separately. We develop and extend the social categorization analysis that lies at the heart of faultline theory to identify a factor that attenuates the negative influence of faultlines: the extent to which the team has shared objectives. The hypothesized moderating role of shared objectives received support in a study of faultlines formed by differences in gender, tenure, and functional background in 42 top management teams. The focus on top management teams has the additional benefit of providing the first test of the relationship between diversity faultlines and objective indicators of organizational performance. We discuss how these findings, and the innovative way in which we operationalized faultlines, extend faultline theory and research as well as offer guidelines to manage diversity faultlines.

Introduction of structural diversity into oligonucleotides containing 6-thioguanine via on-column conjugation

A method is described for the introduction of structural diversity into the thiocarbonyl group of 6-thioguanine within support-bound, fully protected oligonucleotides via 'on-column′ conjugation. 2′-Deoxy-6-thioguanosine with a chemically-labile trigger at its 6-thio function was incorporated at defined sites into chemically synthesized oligonucleotides. Following selective removal of the thio-protection group the support-immobilized oligonucleotides were conjugated with various groups on-column, and then deprotected and purified to produce a number of oligomers each containing a different modified base. Since the modification is accomplished on-column without affecting other functional and protecting groups in the oligomers this method is compatible with introducing structural diversity at multiple sites in DNA. © 2003 Elsevier Science Ltd. All rights reserved.