Leu628 of the KIX domain of CBP is a key residue for the interaction with the MLL transactivation domain

AbstractPhysical interaction between the transactivation domain (TAD) of the mixed-lineage leukemia protein (MLL) and the KIX domain of the cyclic-AMP response element binding protein (CREB) binding protein (CBP) is necessary for MLL-mediated transcriptional activation. We show by alanine-scanning mutagenesis that hydrophobic surface residues of KIX, especially L628, are energetically important for binding the MLL TAD. NMR studies of the KIX-L628A mutant suggest that L628 plays a crucial role in conformational transitions at the MLL binding site, necessary for high affinity interactions with MLL. Unexpectedly, MLL also binds to the c-Myb/phosphorylated kinase-inducible domain of CREB (pKID) site of KIX, highlighting the complex nature of interactions involving intrinsically disordered transcriptional activators.Structured summaryMINT-8044564, MINT-8044580, MINT-8044598, MINT-8044616, MINT-8044634, MINT-8044656:Cbp (uniprotkb:P45481) and MLL (uniprotkb:Q03164) bind (MI:0407) by isothermal titration calorimetry (MI:0065)MINT-8044696:Cbp (uniprotkb:P45481) and MLL (uniprotkb:Q03164) bind (MI:0407) by nuclear magnetic resonance (MI:0077

Central Venous Pressure Reference Points Measured on Post-Mortem Subject

Hemodynamically the central venous pressure should be the same in both the supine and lateral positions. The accurate determination of an external zero reference level corresponding with mid right atrial level would make possible reliable measurements in either position. The purpose of this study was to help determine the reliability of two central venous pressure extrathoracic reference points; the midaxillary line as it intersects the fifth intercostal space for a supine position, the fourth intercostal space within the right sternal border for a side-lying position. Measurements were taken on twenty cadavers during post-mortem examination to determine the relationship of these two reference points to the mid right atrium. Probes were placed in the chest wall at the two reference sites and carefully extended through to the heart. Direct measurements were then taken to determine the distance of the probes from the mid right atrium. Results of this study revealed that there was a significant difference between the midaxillary reference point and the mid right atrium (p\u3c.001). On an average the midaxillary reference point was 2.9 centimeters posterior to the mid right atrium. The data of this study suggest there was no significant difference between the sternal reference point and the mid right atrium (p\u3e.05). However, due to the high variability of the data (SD of 2.55 cms.), there is reason to suggest that this is not conclusive and that the sternal reference point might not be a reliable estimate of the zero point for central venous pressure readings in the side-lying position for a large proportion of patients

Cucumber volatile blend, a promising female-biased lure for Bactrocera cucumis (French 1907) (Diptera: Tephritidae: Dacinae), a pest fruit fly that does not respond to male attractants

Bactrocera cucumis (French 1907), the ‘cucumber fruit fly’, is a horticultural pest in Australia that primarily infests cucurbits and has also been recorded from tomatoes, papaw and several other hosts. It does not respond to known male lures, cue-lure and methyl eugenol, making monitoring and control difficult. A cucumber volatile blend lure was recently developed in Hawaii and found to be an effective female-biased attractant for the melon fly B. cucurbitae. This lure was field tested in north Queensland, Australia in McPhail traps in comparison with orange ammonia, Cera Trap® and a control, and was found to more consistently trap B. cucumis than the other lures. B. cucumis were caught at 41% of the cucumber volatile lure trap clearances, compared with 27% of the orange ammonia, 18% of the Cera Trap and 16% of the control trap clearances. The cucumber volatile lure was more attractive to B. cucumis in low population densities and also trapped B. cucumis earlier on average than the other lures. Data analysed from the site with highest trap catches (Spring Creek) showed that the cucumber volatile lure caught significantly more B. cucumis than the other traps in four of the 11 trap clearance periods, and for the remaining clearances, no other trap type caught significantly more flies than the cucumber volatile lure. The cucumber volatile lure had a strong female-biased attraction but it was not significantly more female-biased than orange ammonia or Cera Trap. Cucumber volatile lure traps were cleaner to service resulting in better quality specimens than the orange ammonia trap or Cera Trap. These findings have potential implications for market access monitoring for determining pest freedom, and for biosecurity monitoring programmes in other countries that wish to detect B. cucumis early

Divergent evolution of protein conformational dynamics in dihydrofolate reductase.

Molecular evolution is driven by mutations, which may affect the fitness of an organism and are then subject to natural selection or genetic drift. Analysis of primary protein sequences and tertiary structures has yielded valuable insights into the evolution of protein function, but little is known about the evolution of functional mechanisms, protein dynamics and conformational plasticity essential for activity. We characterized the atomic-level motions across divergent members of the dihydrofolate reductase (DHFR) family. Despite structural similarity, Escherichia coli and human DHFRs use different dynamic mechanisms to perform the same function, and human DHFR cannot complement DHFR-deficient E. coli cells. Identification of the primary-sequence determinants of flexibility in DHFRs from several species allowed us to propose a likely scenario for the evolution of functionally important DHFR dynamics following a pattern of divergent evolution that is tuned by cellular environment

Family Structure and Psychologyical Health in Young Adults

This study explored the effect of the gendered structure of siblings in intact and non-intact families, on family relations, social support, perceived control, and psychological distress in a sample of 708 young adults (294 males and 414 females) aged between 18 - 21 years. Of the sample 96 were singletons, 208 had both a brother and sister, 206 had a brother and no sister, and 198 had a sister and no brother. While the results show that both the gender of the participants and the gender of the sibling seem to impact on distress and its mediators; the more important factor is the gender of siblings. In essence the presence of a female sibling is associated with more perceived support, control and optimism, and with lower pessimism and psychological distress. The presence of a female is also associated with better family relations overall and it is suggested that the main mechanism for this positive impact of female siblings is through the lowered conflict and increased expressiveness and cohesion experienced in female versus male dominated sibling groups

Sibling constellations and wellbeing in intact and non-intact families

Background: There is little research on the impact of sibling relations on the development of resilience in families experiencing break up. Methods: The role of sex of siblings in family structures was explored in relation to mental health in young adults in a sample of 927 participants (460 males and 467 females), aged 18-21 years old. In addition the potential mediating relationship of family relations, self-efficacy, optimism and social support were added to the mix in order to provide some ex-planatory mechanism for any relationship that might exist. Results: Multivariate analysis of variance and path analysis were used and findings suggest that the presence of a female sib-ling may be a protective factor and may operate through improving family relationships and increasing self-efficacy, optimism, and perceived social support. Conclusions: It is suggested that the sex structure of siblings should be considered in any family focused intervention to improve mental health