‘Inspired and assisted’, or ‘berated and destroyed’? Research leadership, management and performativity in troubled times

Research leadership in Australian universities takes place against a backdrop of policy reforms concerned with measurement and comparison of institutional research performance. In particular, the Excellence in Research in Australian initiative undertaken by the Australian Research Council sets out to evaluate research quality in Australian universities, using a combination of expert review process, and assessment of performance against &lsquo;quality indicators&rsquo;. Benchmarking exercises of this sort continue to shape institutional policy and practice, with inevitable effects on the ways in which research leadership, mentoring and practice are played out within university faculties and departments. In an exploratory study that interviewed 32 Australian academics in universities in four Australian states, we asked participants, occupying formal or informal research leadership roles, to comment on their perceptions of research leadership as envisioned and enacted in their particular workplaces. We found a pervasive concern amongst participants that coalesced around binaries characterized in metaphoric terms of &lsquo;carrots and whips&rsquo;. Research leadership was seen by many as managerial in nature, and as such, largely tethered to instrumentalist notions of productivity and performativity, while research cultures were seen as languishing under the demoralizing weight of reward and punishment systems. Here, we consider what is at stake for the future of the academic workforce under such conditions, arguing that new models of visionary research leadership are urgently needed in the &lsquo;troubled times&rsquo; of techno-bureaucratic university reforms.<br /

Dynamic changes in eIF4F-mRNA interactions revealed by global analyses of environmental stress responses

BACKGROUND: Translation factors eIF4E and eIF4G form eIF4F, which interacts with the messenger RNA (mRNA) 5' cap to promote ribosome recruitment and translation initiation. Variations in the association of eIF4F with individual mRNAs likely contribute to differences in translation initiation frequencies between mRNAs. As translation initiation is globally reprogrammed by environmental stresses, we were interested in determining whether eIF4F interactions with individual mRNAs are reprogrammed and how this may contribute to global environmental stress responses. RESULTS: Using a tagged-factor protein capture and RNA-sequencing (RNA-seq) approach, we have assessed how mRNA associations with eIF4E, eIF4G1 and eIF4G2 change globally in response to three defined stresses that each cause a rapid attenuation of protein synthesis: oxidative stress induced by hydrogen peroxide and nutrient stresses caused by amino acid or glucose withdrawal. We find that acute stress leads to dynamic and unexpected changes in eIF4F-mRNA interactions that are shared among each factor and across the stresses imposed. eIF4F-mRNA interactions stabilised by stress are predominantly associated with translational repression, while more actively initiating mRNAs become relatively depleted for eIF4F. Simultaneously, other mRNAs are insulated from these stress-induced changes in eIF4F association. CONCLUSION: Dynamic eIF4F-mRNA interaction changes are part of a coordinated early translational control response shared across environmental stresses. Our data are compatible with a model where multiple mRNA closed-loop complexes form with differing stability. Hence, unexpectedly, in the absence of other stabilising factors, rapid translation initiation on mRNAs correlates with less stable eIF4F interactions

Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence

Transmissible gastroenteritis virus (TGEV) genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7). Both the mutant and the parental (rTGEV-wt) viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α) phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c), a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the acquisition of gene 7 by the TGEV genome most likely has provided a selective advantage to the virus

Shorter Mandibular Length is Associated with a Greater Fall in AHI with Weight Loss.

RATIONALE: Obesity is a major risk factor towards the development of obstructive sleep apnea, while significant weight loss (both conservatively managed and surgically assisted) has a variable effect upon its severity. Differences in the effect of weight loss on obstructive sleep apnea may be due to underlying craniofacial characteristics. OBJECTIVES: To determine whether craniofacial characteristics can predict OSA treatment response to significant weight loss. METHODS: We analyzed craniofacial measurements from lateral cephalograms performed at baseline on 57 patients enrolled in a previously reported 2-year randomized clinical weight loss trial (laparoscopic adjustable gastric band surgery versus conservatively [dietician and very low calorie diet] treated). Group mean weight loss was ∼ 13% (mean weight loss 131 to 114 kg), with corresponding reduction in mean apnea-hypopnea index (AHI) from 61 to 41 events/h. Computer assisted lateral cephalogram analysis was undertaken by three trained staff blinded to treatment. We analyzed lateral cephalogram and demographic data at baseline (cross-sectional) and change over two years (interventional) in 54 patients. MEASUREMENTS AND MAIN RESULTS: Baseline cross-sectional analysis indicated no cephalometric measurement correlated significantly with baseline AHI when corrected for neck circumference. The percentage change in AHI over 2 years correlated with a shorter menton-gonion distance (i.e., mandibular body length). The % change in AHI correlated with the % weight change (R(2) = 0.25, p < 0.001) and mandibular body length (R(2) = 0.19, p = 0.002). The % change in AHI correlated with combined weight change and mandibular body length (combined R(2) = 0.31, p < 0.001). CONCLUSIONS: Weight loss as a therapeutic option for severe OSA with severe obesity may be predicted by shorter mandibular body length as measured by lateral cephalometry. CITATION: Naughton MT, Monteith BD, Manton DJ, Dever P, Schachter LM, O'Brien PE, Dixon JB. Shorter mandibular length is associated with a greater fall in AHI with weight loss. J Clin Sleep Med 2015;11(4):451–456

Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus

In the original PDF version of this Article, which was published on 16 October 2017, the publication date was incorrectly given as 10 October 2017. This has now been corrected in the PDF; the HTML version of the paper was correct from the time of publication

Abdominal Adiposity Values Associated With Established Body Mass Indexes in White, Black and Hispanic Americans. A Study From the Third National Health and Nutrition Examination Survey

Purpose: To determine whether white, black and hispanic young (17–39 y) and middle-aged (40–59 y) adults, and elderly (60–90 y) Americans have the same values of abdominal adiposity (estimated from waist circumference (WC) at the established levels of overweight (body mass index, BMI 25–29.9 kg/m2) and obesity (BMI≥30 kg/m2). Methods: Data (n=16,120) from the US Third National Health and Nutrition Survey were utilized. Age-adjusted linear regression analyses were used to estimate gender- and ethnic-specific WC values corresponding to overweight and obesity. Receiver operating characteristic (ROC) curves were also employed to determine the choices of WC values corresponding to the established BMI cut-off points. With ROC, gender- and ethnic-specific cut-off points producing the best combination of sensitivity and specificity were selected as optimal thresholds for WC values corresponding to the established BMI cut-off points. Results: WC values associated with the established BMI were lower in blacks and hispanics compared with whites. In men, the WC values that corresponded to overweight ranged from 89 to 106 cm, from 84 to 95 cm, and from 87 to 97 cm in whites, blacks and hispanics, respectively. The corresponding values for obesity ranged from 99 to 110 cm, from 96 to 107 cm, and from 97 to 108 cm. The WC values that corresponded to overweight in women ranged from 82 to 91 cm, from 81 in to 90 cm, and from 83 to 92 cm in whites, blacks and hispanics, respectively. The analogous values for obesity ranged from 94 to 101 cm, from 93 to 100 cm, and from 94 to 101 cm. Conclusions: The lack of higher WC values in blacks (particularly women) and hispanics at the same levels of BMI for whites challenges previously held assumptions regarding the role of abdominal adiposity in cardiovascular disease experienced by non-whites. Defining the anthropometric variables that satisfactorily describe reasons for ethnic differences in cardiovascular disease is one of the challenges for future research