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To inform future research and enhance intercultural learning in higher education, this article presents findings from a scoping review of international evidence on students' attitudes about the importance of diverse people and beliefs in higher education settings. A final sample of 56 studies were analysed for patterns in their methodological approaches, contexts, aims, and results. Findings suggest that students' conceptualisations of diversity are wider than a focus only on culture, race, or ethnicity, and that students across multiple contexts believe that diversity is an inherent, beneficial part of the learning experience. However, there were inconsistent results related to students' beliefs about the efficacy of diversity practices.

Norovirus is the predominant cause of viral gastroenteritis globally with foodborne outbreaks commonly reported. Filter-feeding bivalve molluscan shellfish can become contaminated with norovirus when grown in waters impacted by inadequately treated effluent wastewater, overflows, or other human fecal sources. Contaminated shellfish pose a significant risk to consumers, because combined with a low norovirus infectious dose, oysters and mussels are often eaten raw or lightly cooked resulting in no or minimal virus inactivation, respectively. In addition, shellfish contamination has significant economic impacts on the seafood industry. To improve risk assessments, reverse transcription (RT)-digital droplet PCR (ddPCR) was used to determine the precise norovirus concentrations in 20 shellfish samples, all positive for norovirus genogroup I and/or II (GI or GII) by RT-quantitative PCR (qPCR), and associated with reported norovirus illness in New Zealand. Using RT-ddPCR, total norovirus GI and/or GII concentrations in shellfish ranged between 44 and 4,630 genome copies (GC)/g digestive tissue. Importantly, 40% (8/20) of shellfish samples contained a total norovirus concentration less than 200 GC/g digestive tissue. In parallel, RNase treatment was applied, prior to viral extraction to remove free viral RNA, which subsequently led to average reductions in norovirus GC/g concentration of 37.1% and 19.4% for GI and GII, respectively. These RT-ddPCR data provide valuable evidence for risk assessment of contaminated shellfish and evaluation of safety guidelines and highlight issues associated with setting a safe threshold of norovirus in shellfish.

Abstract In recent decades, the role of tumor biomechanics on cancer cell behavior at the primary site has been increasingly appreciated. However, the effect of primary tumor biomechanics on the latter stages of the metastatic cascade, such as metastatic seeding of secondary sites and outgrowth remains underappreciated. This work sought to address this in the context of triple negative breast cancer (TNBC), a cancer type known to aggressively disseminate at all stages of disease progression. Using mechanically tuneable model systems, mimicking the range of stiffness's typically found within breast tumors, it is found that, contrary to expectations, cancer cells exposed to softer microenvironments are more able to colonize secondary tissues. It is shown that heightened cell survival is driven by enhanced metabolism of fatty acids within TNBC cells exposed to softer microenvironments. It is demonstrated that uncoupling cellular mechanosensing through integrin β1 blocking antibody effectively causes stiff primed TNBC cells to behave like their soft counterparts, both in vitro and in vivo. This work is the first to show that softer tumor microenvironments may be contributing to changes in disease outcome by imprinting on TNBC cells a greater metabolic flexibility and conferring discrete cell survival advantages.

The paper offers a synthesis of findings from an international initiative coordinated by the Asia Productivity Organisation (APO) to measure higher education productivity across nine Asian countries. The paper discusses benefits, barriers, and potential for estimating university productivity across international contexts. Stakeholders from nine participating countries collected and analysed institutional data and reported measurement results. The APO initiative represents the first multi-country test of an adapted productivity measurement model first advanced by the United States National Research Council (NRC). The research provides evidence for proof of concept of the adapted NRC model for use across international contexts. Additional findings demonstrate the range of productivity definitions and interpretations for higher education. The paper concludes by showing priority areas for both targeted and broad developments in research and practice of measuring productivity in higher education.

Abstract Developing protein‐based vaccines against bacteria has proved much more challenging than producing similar immunisations against viruses. Currently, anti‐bacterial vaccines are designed using methods based on reverse vaccinology. These identify broadly conserved, immunogenic proteins using a combination of genomic and high‐throughput laboratory data. While this approach has successfully generated multiple rationally designed formulations that show promising immunogenicity in animal models, few have been licensed. The difficulty of inducing protective immunity in humans with such vaccines mirrors the ability of many bacteria to recolonise individuals despite recognition by natural polyvalent antibody repertoires. As bacteria express too many antigens to evade all adaptive immune responses through mutation, they must instead inhibit the efficacy of such host defences through expressing surface structures that interface with the immune system. Therefore, ‘immune interface interference’ (I3) vaccines that target these features should synergistically directly target bacteria and prevent them from inhibiting responses to other surface antigens. This approach may help us understand the efficacy of the two recently introduced immunisations against serotype B meningococci, which both target the Factor H‐binding protein (fHbp) that inhibits complement deposition on the bacterial surface. Therefore, I3 vaccine designs may help overcome the current challenges of developing protein‐based vaccines to prevent bacterial infections.

Phosphites have been used to control Sudden Oak Death; however, their precise mode of action is not fully understood. To study the mechanism of action of phosphites, we conducted an inoculation experiment on two open-pollinated tanoak families, previously found to be partially resistant. Stems of treatment group individuals were sprayed with phosphite, and seven days later, distal leaves were inoculated with the Sudden Oak Death pathogen Phytophthora ramorum. Leaves from treated and untreated control plants were harvested before and seven days after inoculation, and transcriptomes of both host and pathogen were analyzed. We found that tanoak families differed in the presence of innate resistance (resistance displayed by untreated tanoak) and in the response to phosphite treatment. A set of expressed genes associated with innate resistance was found to overlap with an expressed gene set for phosphite-induced resistance. This observation may indicate that phosphite treatment increases the resistance of susceptible host plants. In addition, genes of the pathogen involved in detoxification were upregulated in phosphite-treated plants compared to phosphite-untreated plants. In summary, our RNA-Seq analysis supports a two-fold mode of action of phosphites, including a direct toxic effect on P. ramorum and an indirect enhancement of resistance in the tanoak host.

ATP13A2 is a lysosomal protein involved in polyamine transport with loss of function mutations associated with multiple neurodegenerative conditions. These include early onset Parkinson’s disease, Kufor-Rakeb Syndrome, neuronal ceroid lipofuscinosis, hereditary spastic paraplegia, and amyotrophic lateral sclerosis. While ATP13A2 mutations may result in clinical heterogeneity, the basal ganglia appear to be impacted in the majority of cases. The basal ganglia is particularly vulnerable to environmental exposures such as heavy metals, pesticides, and industrial agents which are also established risk factors for many neurodegenerative conditions. Not surprisingly then, impaired function of ATP13A2 has been linked to heavy metal toxicity including manganese, iron, and zinc. This review discusses the role of ATP13A2 in basal ganglia function and dysfunction, potential common pathological mechanisms in ATP13A2-related disorders, and how gene x environment interactions may contribute to basal ganglia dysfunction.

Abstract Objectives Patients with rheumatoid arthritis (RA) have an increased susceptibility to infections, including those caused by Streptococcus pneumoniae. Why RA is associated with increased susceptibility to S. pneumoniae is poorly understood. This study aims to assess the effects of RA and B‐cell depletion therapy on naturally acquired antibody responses to 289 S. pneumoniae protein antigens using a novel protein array. Methods IgG responses to S. pneumoniae were characterised in serum from RA patients and disease controls (myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)) using whole‐cell ELISA, a flow cytometry opsonisation assay and an S. pneumoniae protein array. For the RA patients, results were compared before and after B‐cell depletion therapy. Results Compared to a well‐characterised disease control group of ME/CFS patients, RA patients had reduced antibody responses to multiple S. pneumoniae protein antigens, with significant IgG recognition of approximately half the number of antigens along with reduced median strengths of these responses. Reduction in multiple array antigen‐specific responses also correlated with reduced IgG opsonisation of S. pneumoniae. Although B‐cell depletion therapy with rituximab did not reduce overall IgG recognition of S. pneumoniae in the RA group, it was associated with marked disruption of pre‐existing IgG repertoire to protein antigens in individual patients. Conclusion These data show RA is associated with major disruption of naturally acquired adaptive immunity to S. pneumoniae, which can be assessed rapidly using a protein antigen array and is likely to contribute towards the increased incidence of pneumonia in patients with RA.

Leadership matters for the success of large enterprises and this is also the case for higher education institutions and universities. Yet, the public nature of universities and of academia means these institutions are usually highly dependent on external actors, in particular government. Viewed through a lens of distributed leadership, this paper explores how leaders in universities, national academies and government view and rate key changes associated with this pervasive reorientation and reorganisation of public higher education. It asks where do the views of leaders within universities and those outside universities converge and diverge and what patterns are evident in the differences between leaders? Drawing on 116 in-depth interviews and 114 follow-up surveys with senior higher education leaders in Australia, of which just over half were university senior executives, this paper concludes that all leaders surveyed are largely aligned in their views of most issues.

Abstract Background The respiratory pathogen Streptococcus pneumoniae (the pneumococcus) is a genetically diverse bacterium associated with over 101 immunologically distinct polysaccharide capsules (serotypes). Polysaccharide conjugate vaccines (PCVs) have successfully eliminated multiple targeted serotypes, yet the mucoid serotype 3 has persisted despite its inclusion in PCV13. This capsule type is predominantly associated with a single globally disseminated strain, GPSC12 (clonal complex 180). Methods A genomic epidemiology study combined previous surveillance datasets of serotype 3 pneumococci to analyse the population structure, dynamics, and differences in rates of diversification within GPSC12 during the period of PCV introductions. Transcriptomic analyses, whole genome sequencing, mutagenesis, and electron microscopy were used to characterise the phenotypic impact of loci hypothesised to affect this strain’s evolution. Results GPSC12 was split into clades by a genomic analysis. Clade I, the most common, rarely underwent transformation, but was typically infected with the prophage ϕOXC141. Prior to the introduction of PCV13, this clade’s composition shifted towards a ϕOXC141-negative subpopulation in a systematically sampled UK collection. In the post-PCV13 era, more rapidly recombining non-Clade I isolates, also ϕOXC141-negative, have risen in prevalence. The low in vitro transformation efficiency of a Clade I isolate could not be fully explained by the ~100-fold reduction attributable to the serotype 3 capsule. Accordingly, prophage ϕOXC141 was found to modify csRNA3, a non-coding RNA that inhibits the induction of transformation. This alteration was identified in ~30% of all pneumococci and was particularly common in the unusually clonal serotype 1 GPSC2 strain. RNA-seq and quantitative reverse transcriptase PCR experiments using a genetically tractable pneumococcus demonstrated the altered csRNA3 was more effective at inhibiting production of the competence-stimulating peptide pheromone. This resulted in a reduction in the induction of competence for transformation. Conclusion This interference with the quorum sensing needed to induce competence reduces the risk of the prophage being deleted by homologous recombination. Hence the selfish prophage-driven alteration of a regulatory RNA limits cell-cell communication and horizontal gene transfer, complicating the interpretation of post-vaccine population dynamics.

The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease.

The distribution and organisation of matrix molecules in the tumour stroma help shape solid tumour progression. Here they perform temporal proteomic profiling of the matrisome during breast cancer progression and show that collagen XII secreted from CAFs provides a pro-invasive microenvironment.

Abstract Background Smokeless tobacco (ST) is consumed globally by more than 350 million people, with approximately 85% of all users based in South and Southeast Asia. In this region, ST products are cheap and easily accessible. Evidence-based interventions to people quit ST use are lacking. This study aims to test the feasibility of conducting a future definitive trial of ST cessation, using a culturally adapted behavioural intervention, and/or nicotine replacement therapy (NRT) in three South Asian countries. Methods We will conduct a factorial design, randomised-controlled pilot trial in Bangladesh, India and Pakistan. Daily ST users will be recruited from primary health care settings in Dhaka, Noida and Karachi. Participants will be individually randomised to receive intervention A (4 or 6 mg NRT chewing gum for 8-weeks), intervention B (BISCA: face-to-face behavioural support for ST cessation), a combination of interventions A and B or usual care (Very Brief Advice - VBA). The participants will provide demographic and ST use related data at baseline, and at 6, 12 and 26 weeks of follow-up. Salivary cotinine samples will be collected at baseline and 26 weeks. The analyses will undertake an assessment of the feasibility of recruitment, randomisation, data collection and participant retention, as well as the feasibility of intervention delivery. We will also identify potential cessation outcomes to inform the main trial, understand the implementation, context and mechanisms of impact through a process evaluation and, thirdly, establish health resource use and impact on the quality of life through health economic data. Discussion The widespread and continued use of ST products in South Asia is consistent with a high rate of associated diseases and negative impact on the quality of life. The identification of feasible, effective and cost-effective interventions for ST is necessary to inform national and regional efforts to reduce ST use at the population level. The findings of this pilot trial will inform the development of larger trials for ST cessation among South Asian users, with relevance to wider regions and populations having high rates of ST use. Trial registration ISRCTN identifier 65109397

Abstract Background This study applies the Patient Self-Advocacy scale to investigate vaccine hesitancy in New Zealand. Due to New Zealand’s very limited tertiary hospital system and vulnerable populations, the Government’s strategy to address COVID-19 has been to prevent the virus from entering the nation and to eliminate it when it does cross the border. Therefore, there is no opportunity for the nation to generate any acquired immunity through exposure. To transition from closed borders, New Zealand will need to run a highly successful national vaccination programme and this needs to have the ability to drive influential public health messaging to the targeted places within the communities where vaccine hesitancy most exists. Methods This study employed statistical methods. A nationally representative survey of adults in New Zealand (n = 1852) was collected via Qualtrics. Independent samples t-tests, and multiple regression were used to explore the research questions. Results Those who identify as medically able to be vaccinated expressed significantly higher confidence in the COVID-19 vaccine than those who identified as unable to be vaccinated. Patient-self advocacy had a positive effect on vaccine confidence. Individuals who identify as able to be vaccinated have less hesitancy. Demographics had various effects on vaccine hesitancy. Conclusion The research highlights particularly important insights into vaccine hesitancy related to patient self-advocacy behaviours, and various demographic variables such as political affiliation. In addition, the research adds further clarity on how and why New Zealanders have responded to the COVID-vaccine. Finally, the importance of vaccine literacy is discussed.

The United States has been the leader in fundamental research for the last seven decades. Fundamental research is overwhelming undertaken in or in conjunction with research-intensive universities, and since the 1950s they have depended on US Federal funding to make this possible. This support has been consistently championed by Congress, is popular across the political spectrum and enjoys long public backing, in no small part because there remains a widespread trust in the societal benefits it provides. Yet the US now faces a dilemma over the future of this national achievement and the supporting arrangements making it sustainable. The ‘social contract’ for science and research now looks more tentative than at any time since the Space Race. This paper examines why many US university leaders, faculty, experts and policy-makers are increasingly concerned, what is driving this and how they are responding. Building on 37 interviews with university, academic and government leaders, this study uses a mixed methodology to explore perceived institutional challenges and the politics around them, alongside the responses and strategies of US research-intensive universities in the context of global, national and regional policies. This paper examines tensions in the relationship between universities and government, and between researcher and public, combining perspectives from a sample of leading research universities and from national policy leaders to offer insight into the intersection of Federal policy and local operationalization. It concludes that for the future of US basic science and research two factors are likely to be decisive, being whether the strength of the public backing for funding university-based fundamental research continues, and how universities respond if, and in the assessment of many, when this support erodes. If the current research system is to remain viable, universities will need to make greater efforts to rebuild trust and understanding with the US public and litigate anew their raison d'etre at the center of US research.

Streptococcus pneumoniae (the pneumococcus) is the major cause of bacterial pneumonia in the US and worldwide. Studies have shown that the differing chemical make-up between serotypes of its most important virulence factor, the capsule, can dictate disease severity. Here we demonstrate that control of capsule synthesis is also critical for infection and facilitated by two broadly conserved transcription factors, SpxR and CpsR, through a distal cis-regulatory element we name the 37-CE. Strikingly, changing only three nucleotides within this sequence is sufficient to render pneumococcus avirulent. Using in vivo and in vitro approaches, we present a model where SpxR interacts as a unique trimeric quaternary structure with the 37-CE to enable capsule repression in the airways. Considering its dramatic effect on infection, variation of the 37-CE between serotypes suggests this molecular switch could be a critical contributing factor to this pathogen’s serotype-specific disease outcomes. Author summary Streptococcus pneumoniae (the pneumococcus) is a Gram-positive pathogen that causes significant morbidity and mortality in the US and worldwide. The pneumococcus first colonizes the upper respiratory tract asymptomatically, and then drops into the lung to cause pneumonia, followed by sepsis (blood infection), where patient mortality rates exceed 20%. Studies have indicated that the reason S. pneumoniae can survive in the blood so well is due to its protective polysaccharide capsule. This vital virulence factor acts as a sugary coat which shields the bacterium from immune detection, opsonization, and phagocytosis. However, how this metabolically expensive virulence factor is regulated during colonization, lung infection, and sepsis has remained enigmatic. Here we describe two transcription factors, SpxR and CpsR, which repress capsule biosynthesis in the airways through a small, conserved, regulatory piece of DNA (the 37-CE) until the onset of sepsis–where repression is relieved, allowing for increased capsule biosynthesis, and by association, the high mortality associated with this condition. The 37-CE varies considerably among the 100+ pneumococcal serotypes, each of which has a chemically-distinct capsule composition. This may, in part, explain the variation in serotype-dependent disease severity we have observed for decades.

BackgroundLong-term immunity to SARS-CoV-2 infection, including neutralizing antibodies and T cell-mediated immunity, is required in a very large majority of the population in order to reduce ongoing disease burden.MethodsWe have investigated the association between memory CD4 and CD8 T cells and levels of neutralizing antibodies in convalescent COVID-19 subjects.FindingsHigher titres of convalescent neutralizing antibodies were associated with significantly higher levels of RBD-specific CD4 T cells, including specific memory cells that proliferated vigorously in vitro. Conversely, up to half of convalescent individuals had low neutralizing antibody titres together with a lack of receptor binding domain (RBD)-specific memory CD4 T cells. These low antibody subjects had other, non-RBD, spike-specific CD4 T cells, but with more of an inhibitory Foxp3+ and CTLA-4+ cell phenotype, in contrast to the effector T-bet+, cytotoxic granzymes+ and perforin+ cells seen in RBD-specific memory CD4 T cells from high antibody subjects. Single cell transcriptomics of antigen-specific CD4+ T cells from high antibody subjects similarly revealed heterogenous RBD-specific CD4+ T cells that comprised central memory, transitional memory and Tregs, as well as cytotoxic clusters containing diverse TCR repertoires, in individuals with high antibody levels. However, vaccination of low antibody convalescent individuals led to a slight but significant improvement in RBD-specific memory CD4 T cells and increased neutralizing antibody titres.InterpretationOur results suggest that targeting CD4 T cell epitopes proximal to and within the RBD-region should be prioritized in booster vaccines.