cDNA-RNA subtractive hybridization reveals increased expression of mycocerosic acid synthase in intracellular Mycobacterium bovis BCG.

Identifying genes that are differentially expressed by Mycobacterium bovis BCG after phagocytosis by macrophages will facilitate the understanding of the molecular mechanisms of host cell-intracellular pathogen interactions. To identify such genes a cDNA-total RNA subtractive hybridization strategy has been used that circumvents the problems both of limited availability of bacterial RNA from models of infection and the high rRNA backgrounds in total bacterial RNA. The subtraction products were used to screen a high-density gridded Mycobacterium tuberculosis genomic library. Sequence data were obtained from 19 differential clones, five of which contained overlapping sequences for the gene encoding mycocerosic acid synthase (mas). Mas is an enzyme involved in the synthesis of multi-methylated long-chain fatty acids that are part of phthiocerol dimycocerosate, a major component of the complex mycobacterial cell wall. Northern blotting and primer extension data confirmed up-regulation of mas in intracellular mycobacteria and also revealed a putative extended -10 promoter structure and a long untranslated upstream region 5' of the mas transcripts, containing predicted double-stranded structures. Furthermore, clones containing overlapping sequences for furB, groEL-2, rplE and fadD28 were identified and the up-regulation of these genes was confirmed by Northern blot analysis. The cDNA-RNA subtractive hybridization enrichment and high density gridded library screening, combined with selective extraction of bacterial mRNA represents a valuable approach to the identification of genes expressed during intra-macrophage residence for bacteria such as M. bovis BCG and the pathogenic mycobacterium, M. tuberculosis

A Faculty-Based Mentorship Circle: Positioning New Faculty for Success

Multiple and competing priorities within a dynamic and changing academic environment can pose significant challenges for new faculty. Mentorship has been identified as an important strategy to help socialize new faculty to their roles and the expectations of the academic environment. It also helps them learn new skills that will position them to be successful in their academic career. In this article, the authors report on the implementation and evaluation of a mentorship circle initiative aimed at supporting new faculty in the first two years of their academic appointment. Participants reported that the mentorship circle provided them with a culture of support, a sense of belonging, and a safe space to discuss concerns and learn strategies from both mentors and fellow mentees as they adjusted to their new position. The interdisciplinary nature of the mentorship circle further facilitated faculty members’ capacity to navigate their role as new faculty and foster colleagueship.  Dans un milieu universitaire dynamique et évolutif, des priorités diverses et contradictoires peuvent représenter des défis importants pour les nouveaux membres du corps professoral. Le mentorat a été identifié comme une stratégie importante qui aide les nouveaux membres du corps professoral à socialiser dans le cadre de leurs fonctions et à répondre aux attentes du milieu universitaire. Le mentorat les aide aussi à acquérir de nouvelles compétences qui les prépareront à réussir leur carrière universitaire. Dans cet article, les auteurs font état de la mise en œuvre et de l’évaluation d’un cercle de mentorat visant à soutenir les nouveaux membres du corps professoral au cours de leurs deux premières années en fonction. Les participants ont signalé que le cercle de mentorat leur avait offert une culture de soutien, un sentiment d’appartenance et un espace sûr pour discuter de leurs préoccupations et acquérir, grâce au contact des mentors et d’autres collègues du cercle, des stratégies pour s’adapter à leur nouveau rôle. La nature interdisciplinaire du cercle de mentorat a facilité davantage la capacité des membres du corps enseignant à mener leur rôle et à cultiver des relations collégiales

Sweet taste and nutrient value subdivide rewarding dopaminergic neurons in Drosophila

Dopaminergic neurons provide reward learning signals in mammals and insects [1-4]. Recent work in Drosophila has demonstrated that water-reinforcing dopaminergic neurons are different to those for nutritious sugars [5]. Here, we tested whether the sweet taste and nutrient properties of sugar reinforcement further subdivide the fly reward system. We found that dopaminergic neurons expressing the OAMB octopamine receptor [6] specifically convey the short-term reinforcing effects of sweet taste [4]. These dopaminergic neurons project to the beta\u272 and gamma4 regions of the mushroom body lobes. In contrast, nutrient-dependent long-term memory requires different dopaminergic neurons that project to the gamma5b regions, and it can be artificially reinforced by those projecting to the beta lobe and adjacent alpha1 region. Surprisingly, whereas artificial implantation and expression of short-term memory occur in satiated flies, formation and expression of artificial long-term memory require flies to be hungry. These studies suggest that short-term and long-term sugar memories have different physiological constraints. They also demonstrate further functional heterogeneity within the rewarding dopaminergic neuron population

Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions

Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis

Retroposed Elements as Archives for the Evolutionary History of Placental Mammals

Reconstruction of the placental mammalian (eutherian) evolutionary tree has undergone diverse revisions, and numerous aspects remain hotly debated. Initial hierarchical divisions based on morphology contained many misgroupings due to features that evolved independently by similar selection processes. Molecular analyses corrected many of these misgroupings and the superordinal hierarchy of placental mammals was recently assembled into four clades. However, long or rapid evolutionary periods, as well as directional mutation pressure, can produce molecular homoplasies, similar characteristics lacking common ancestors. Retroposed elements, by contrast, integrate randomly into genomes with negligible probabilities of the same element integrating independently into orthologous positions in different species. Thus, presence/absence analyses of these elements are a superior strategy for molecular systematics. By computationally scanning more than 160,000 chromosomal loci and judiciously selecting from only phylogenetically informative retroposons for experimental high-throughput PCR applications, we recovered 28 clear, independent monophyly markers that conclusively verify the earliest divergences in placental mammalian evolution. Using tests that take into account ancestral polymorphisms, multiple long interspersed elements and long terminal repeat element insertions provide highly significant evidence for the monophyletic clades Boreotheria (synonymous with Boreoeutheria), Supraprimates (synonymous with Euarchontoglires), and Laurasiatheria. More importantly, two retropositions provide new support for a prior scenario of early mammalian evolution that places the basal placental divergence between Xenarthra and Epitheria, the latter comprising all remaining placentals. Due to its virtually homoplasy-free nature, the analysis of retroposon presence/absence patterns avoids the pitfalls of other molecular methodologies and provides a rapid, unequivocal means for revealing the evolutionary history of organisms

WALLABY Early Science - I. The NGC 7162 Galaxy Group

We present Widefield ASKAP L-band Legacy All-sky Blind Survey (WALLABY) early science results from the Australian Square Kilometre Array Pathfinder (ASKAP) observations of the NGC 7162 galaxy group. We use archival HIPASS and Australia Telescope Compact Array (ATCA) observations of this group to validate the new ASKAP data and the data reduction pipeline ASKAPsoft. We detect six galaxies in the neutral hydrogen (HI) 21-cm line, expanding the NGC 7162 group membership from four to seven galaxies. Two of the new detections are also the first HI detections of the dwarf galaxies, AM 2159-434 and GALEXASC J220338.65-431128.7, for which we have measured velocities of $cz=2558$ and $cz=2727$ km s$^{-1}$, respectively. We confirm that there is extended HI emission around NGC 7162 possibly due to past interactions in the group as indicated by the $40^{\circ}$ offset between the kinematic and morphological major axes for NGC 7162A, and its HI richness. Taking advantage of the increased resolution (factor of $\sim1.5$) of the ASKAP data over archival ATCA observations, we fit a tilted ring model and use envelope tracing to determine the galaxies' rotation curves. Using these we estimate the dynamical masses and find, as expected, high dark matter fractions of $f_{\mathrm{DM}}\sim0.81-0.95$ for all group members. The ASKAP data are publicly available.Comment: 20 pages, 11 figures, accepted for publication in MNRA

Brief biopsychosocially informed education can improve insurance workers' back pain beliefs: Implications for improving claims management behaviours

Background: Biopsychosocially informed education is associated with improved back pain beliefs and positive changes in health care practitioners’ practice behaviours. Objective: Assess the effect of this type of education for insurance workers who are important non-clinical stakeholders in the rehabilitation of injured workers. Methods: Insurance workers operating in the Western Australian workers’ compensation system underwent two, 1.5 hour sessions of biopsychosocially informed education focusing on understanding and identifying barriers to recovery of injured workers with musculoskeletal conditions. Back pain beliefs were assessed pre-education, immediately post-education and at three-month follow-up (n = 32). Self-reported and Injury Management Advisor-reported assessment of change in claims management behaviours were collected at the three-month follow-up. Results: There were positive changes in the Health Care Providers’ Pain and Impairment Relationship Scale (p = 0.009) and Back Beliefs Questionnaire (p = 0.049) immediately following the education that were sustained at three-month follow-up. Positive changes in claims management behaviours were supported by self-reported and Injury Management Advisor-reported data. Conclusion: This study provides preliminary support that a brief biopsychosocially informed education program can positively influence insurance workers’ beliefs regarding back pain, with concurrent positive changes in claims management behaviours. Further research is required to ascertain if these changes result in improved claims management outcomes