The unique chemistry of Eastern Mediterranean water masses selects for distinct microbial communities by depth

Peer reviewedPublisher PD

Evaluating efficacy of a ballast water filtration system for reducing spread of aquatic species in freshwater ecosystems

Biological invasions by non-indigenous species are considered a leading threat to biodiversity, with prevention being a key management strategy. Consequently, numerous commercial ballast water treatment systems have been, or are being, developed to prevent future aquatic invasions. However, most treatment systems are being designed for the many vessels undertaking long transoceanic voyages in marine waters rather than the relatively few vessels operating on short voyages in freshwater, such as those in the Laurentian Great Lakes. Here we conduct testing of the biological efficacy of a 40 µm ballast water filtration unit through shipboard trials. We test the hypotheses that i) filtration will significantly reduce abundance of zooplankton greater than 50 µm in size but not phytoplankton 10 to 50 µm in size; ii) filtration will reduce zooplankton abundances in ballast water below International Maritime Organization discharge standards, but not those of phytoplankton; and iii) filtration will alter the community composition of zooplankton, non-randomly reducing invasion risk of larger taxa. During the summer of 2012, three shipboard trials were conducted. Ballast water samples were collected using a before-after experimental design. Our study showed that filtration significantly reduced abundance of copepods and cladocerans, but not of juvenile dreissenid veligers and rotifers. Contrary to our expectation, phytoplankton densities were also significantly lower after the treatment. Overall, ballast water treated during our tests would not meet proposed international discharge standards. Filtration altered relative abundance of zooplankton, but did not reduce introduction risk of any taxonomic group due to the small juvenile stages and dormant eggs which passed through the treatment. While we do not rule out filtration as a ballast water treatment option for zooplankton in the future, our tests indicate further development is required for meaningful reduction of invasion risk

Characterization of potential biomarkers of reactogenicity of licensed antiviral vaccines: randomized controlled clinical trials conducted by the BIOVACSAFE consortium

Funding text The authors are grateful for the vital contributions of the participating study volunteers, clinicians, nurses, and laboratory technicians at the Surrey study site. The work by Roberto Leone, laboratory technician at Humanitas Clinical and Research Center, is gratefully acknowledged. Finally, they thank Ellen Oe (GSK) for scientific writing assistance. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115308, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in-kind contribution. The contribution of the European Commission to the Advanced Immunization Technologies (ADITEC) project (grant agreement n° 280873) is also gratefully acknowledged. Publisher Copyright: © 2019, The Author(s).Biomarkers predictive of inflammatory events post-vaccination could accelerate vaccine development. Within the BIOVACSAFE framework, we conducted three identically designed, placebo-controlled inpatient/outpatient clinical studies (NCT01765413/NCT01771354/NCT01771367). Six antiviral vaccination strategies were evaluated to generate training data-sets of pre-/post-vaccination vital signs, blood changes and whole-blood gene transcripts, and to identify putative biomarkers of early inflammation/reactogenicity that could guide the design of subsequent focused confirmatory studies. Healthy adults (N = 123; 20–21/group) received one immunization at Day (D)0. Alum-adjuvanted hepatitis B vaccine elicited vital signs and inflammatory (CRP/innate cells) responses that were similar between primed/naive vaccinees, and low-level gene responses. MF59-adjuvanted trivalent influenza vaccine (ATIV) induced distinct physiological (temperature/heart rate/reactogenicity) response-patterns not seen with non-adjuvanted TIV or with the other vaccines. ATIV also elicited robust early (D1) activation of IFN-related genes (associated with serum IP-10 levels) and innate-cell-related genes, and changes in monocyte/neutrophil/lymphocyte counts, while TIV elicited similar but lower responses. Due to viral replication kinetics, innate gene activation by live yellow-fever or varicella-zoster virus (YFV/VZV) vaccines was more suspended, with early IFN-associated responses in naïve YFV-vaccine recipients but not in primed VZV-vaccine recipients. Inflammatory responses (physiological/serum markers, innate-signaling transcripts) are therefore a function of the vaccine type/composition and presence/absence of immune memory. The data reported here have guided the design of confirmatory Phase IV trials using ATIV to provide tools to identify inflammatory or reactogenicity biomarkers.Peer reviewe

The helicase HAGE prevents interferon-a-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1

The tumour suppressor PML (promyelocytic leukaemia protein) regulates several cellular pathways involving cell growth, apoptosis, differentiation and senescence. PML also has an important role in the regulation of stem cell proliferation and differentiation. Here, we show the involvement of the helicase HAGE in the transcriptional repression of PML expression in ABCB5 + malignant melanoma-initiating cells (ABCB5 + MMICs), a population of cancer stem cells which are responsible for melanoma growth, progression and resistance to drug-based therapy. HAGE prevents PML gene expression by inhibiting the activation of the JAK-STAT (janus kinase-signal transducers and activators of transcription) pathway in a mechanism which implicates the suppressor of cytokine signalling 1 (SOCS1). Knockdown of HAGE led to a significant decrease in SOCS1 protein expression, activation of the JAK-STAT signalling cascade and a consequent increase of PML expression. To confirm that the reduction in SOCS1 expression was dependent on the HAGE helicase activity, we showed that SOCS1, effectively silenced by small interfering RNA, could be rescued by re-introduction of HAGE into cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes SOCS1 mRNA unwinding and protein expression in vitro

Bridging the gap: the challenges of employing entrepreneurial processes within university settings

In Australia and elsewhere, universities face increasing pressure to improve research output and quality, particularly through partnerships with industry. This raises interesting challenges for academic staff with considerable industry experience who are ‘new’ to academe. Some of these challenges were faced by the authors who have been successful in generating research, consultancy and executive education funds since joining academe and been somewhat surprised at being described as successful researchers and entrepreneurs. Taking a reflexive look to identify and make explicit our practice through the lenses of social capital and the entrepreneurial process, we identified 10 practices. However, we remain troubled by the dissonance between organisational rhetoric and its rewards for entrepreneurial activities. We offer some considerations for universities to help bridge this gap

The ‘double-edged sword’ of a sessional academic career

There have been widespread changes to working arrangements and employment relationships, including significant decreases in continuing/full-time employment contracts. This trend is particularly notable in academia, with more universities relying on the expertise of sessional, teaching-focused academics. This qualitative study extends understanding of this important group of professionals, identifying sessional work as a ‘double-edged sword’ and suggesting a typology of sessional academic careers to be tested in future research. It reports on the diversity among sessional academics, some enjoying the autonomy and flexibility of this working arrangement, others seeking more job security and greater alignment with continuing employment. It also identifies synergies and contradictions between sessional academic careers and key themes in the contemporary careers literature

A proteomic study of human Merkel Cell Carcinoma

Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine cancer of the skin. The incidence has been quadrupled with a 5-year mortality rate of 46%, presently there is no cure for metastatic disease. Despite the contribution of Merkel cell polyomavirus, the molecular events of MCC carcinogenesis are poorly defined. To better understand MCC carcinogensis, we have performed the first quantitative proteomic comparison of formalin-fixed, paraffin-embedded (FFPE) MCC tissues using another neuroendocrine tumor (carcinoid tumor of the lung) as controls. Bioinformatic analysis of the proteomic data has revealed that MCCs carry distinct protein expression patterns. Further analysis of significantly over-expressed proteins suggested the involvement of MAPK, PI3K/Akt/mTOR, wnt, and apoptosis signaling pathways. Our previous study and that from others have shown mTOR activation in MCCs. Therefore, we have focused on two downstream molecules of the mTOR pathway, lactate dehydrogenase B (LDHB) and heterogeneous ribonucleoprotein F (hnRNPF). We confirm over-expression of LDHB and hnRNPF in two primary human MCC cell lines, 16 fresh tumors, and in the majority of 80 tissue microarray samples. Moreover, mTOR inhibition suppresses LDHB and hnRNPF expression in MCC cells. The results of the current study provide insight into MCC carcinogenesis and provide rationale for mTOR inhibition in pre-clinical studies

How robust are value judgements of health inequality aversion? Testing for framing and cognitive effects

Background: Empirical studies have found that members of the public are inequality averse and value health gains for disadvantaged groups with poor health many times more highly than gains for better off groups. However, these studies typically use abstract scenarios that involve unrealistically large reductions in health inequality, and face-to-face survey administration. It is not known how robust these findings are to more realistic scenarios or anonymous online survey administration. Methods: This study aimed to test the robustness of questionnaire estimates of inequality aversion by comparing the following: (1) small versus unrealistically large health inequality reductions; (2) population-level versus individual-level descriptions of health inequality reductions; (3) concrete versus abstract intervention scenarios; and (4) online versus face to face mode of administration. Fifty-two members of the public participated in face-to-face discussion groups, while 83 members of the public completed an online survey. Participants were given a questionnaire instrument with different scenario descriptions for eliciting aversion to social inequality in health. Results: The median respondent was inequality averse under all scenarios. Scenarios involving small rather than unrealistically large health gains made little difference in terms of inequality aversion, as did population-level rather than individual-level scenarios. However, the proportion expressing extreme inequality aversion fell 19 percentage points when considering a specific health intervention scenario rather than an abstract scenario, and was 11-21 percentage points lower among online public respondents compared to the discussion group. Conclusions: Our study suggests that both concrete scenarios and online administration reduce the proportion expressing extreme inequality aversion but still yield median responses implying substantial health inequality aversion

Spectrally and Radiometrically Stable, Wideband, Onboard Calibration Source

The Onboard Calibration (OBC) source incorporates a medical/scientific-grade halogen source with a precisely designed fiber coupling system, and a fiber-based intensity-monitoring feedback loop that results in radiometric and spectral stabilities to within less than 0.3 percent over a 15-hour period. The airborne imaging spectrometer systems developed at the Jet Propulsion Laboratory incorporate OBC sources to provide auxiliary in-use system calibration data. The use of the OBC source will provide a significant increase in the quantitative accuracy, reliability, and resulting utility of the spectral data collected from current and future imaging spectrometer instruments