Search

BackgroundMicrobial keratitis is one of the leading causes of blindness globally. An overactive immune response during an infection can exacerbate damage, causing corneal opacities and vision loss. This study aimed to identify the differentially expressed genes between corneal infection patients and healthy volunteers within the cornea and conjunctiva and elucidate the contributing pathways to these conditions’ pathogenesis. Moreover, it compared the corneal and conjunctival transcriptomes in corneal-infected patients to cytokine levels in tears.MethodsCorneal and conjunctival swabs were collected from seven corneal infection patients and three healthy controls under topical anesthesia. RNA from seven corneal infection patients and three healthy volunteers were analyzed by RNA sequencing (RNA-Seq). Tear proteins were extracted from Schirmer strips via acetone precipitation from 38 cases of corneal infection and 14 healthy controls. The cytokines and chemokines IL-1β, IL-6, CXCL8 (IL-8), CX3CL1, IL-10, IL-12 (p70), IL-17A, and IL-23 were measured using an antibody bead assay.ResultsA total of 512 genes were found to be differentially expressed in infected corneas compared to healthy corneas, with 508 being upregulated and four downregulated (fold-change (FC) 2 and adjusted p

The data presented in this article are related to the research article entitled "The autoimmune risk gene ZMIZ1 is a vitamin D responsived marker of a molecular phenotype of multiple sclerosis" Fewings et al. (2017) [1]. Here we identify the set of genes correlated with ZMIZ1 in multiple cohorts, provide phenotypic details on those cohorts, and identify the genes negatively correlated with ZMIZ1 and the cells predominantly expressing those genes. We identify the metabolic pathways in which the molecular phenotype genes are over-represented. Finally, we present the flow cytometry gating strategy we have used to identify the immune cells from blood which are producing ZMIZ1 and RPS6.

Abstract Background The mechanisms linking UV radiation and vitamin D exposure to the risk of acquiring the latitude and critical period-dependent autoimmune disease, multiple sclerosis, is unclear. We examined the effect of vitamin D on DNA methylation and DNA methylation at vitamin D receptor binding sites in adult and paediatric myeloid cells. This was accomplished through differentiating CD34+ haematopoietic progenitors into CD14+ mononuclear phagocytes, in the presence and absence of calcitriol. Results Few DNA methylation changes occurred in cells treated with calcitriol. However, several VDR-binding sites demonstrated increased DNA methylation in cells of adult origin when compared to cells of paediatric origin. This phenomenon was not observed at other transcription factor binding sites. Genes associated with these sites were enriched for intracellular signalling and cell activation pathways involved in myeloid cell differentiation and adaptive immune system regulation. Conclusion These results suggest vitamin D exposure at critical periods during development may contribute to latitude-related differences in autoimmune disease incidence.

Among modern biomaterials, hybrid tools containing an organic component and a metal cation are recognized as added value, and, for many advanced biomedical applications, synthetic polymers are used as thin protective/functional coatings for medical or prosthetic devices and implants. These materials require specific non-degradability, biocompatibility, antimicrobial, and antiproliferative properties to address safety aspects concerning their use in medicine. Moreover, bioimaging monitoring of the biomedical device and/or implant through biological tissues is a desirable ability. This article reports a novel hybrid metallopolymer obtained by grafting zinc-coordinated fragments to an organic polymeric matrix. This hybrid polymer, owing to its relevant emission in the deep red to near-infrared (DR/NIR) region, is monitorable; therefore, it represents a potential material for biomedical coating. Furthermore, it shows good biocompatibility and adhesion properties and excellent stability in slightly acidic/basic water solutions. Finally, in contact with the superficial layers of human skin, it shows antimicrobial properties against Staphylococcus aureus bacterial strains.

Multiple Sclerosis (MS) is a complex immune-mediated disease of the central nervous system. Treatment is based on immunomodulation, including specifically targeting B cells. B cells are the main host for the Epstein-Barr Virus (EBV), which has been described as necessary for MS development. Over 200 genetic loci have been identified as increasing susceptibility to MS. Many MS risk genes have altered expression in EBV infected B cells, dependent on the risk genotype, and are themselves regulated by the EBV transcription factor EBNA2. Females are 2-3 times more likely to develop MS than males. We investigated if MS risk loci might mediate the gender imbalance in MS. From a large public dataset, we identified gender-specific associations with EBV traits, and MS risk SNP/gene pairs with gender differences in their associations with gene expression. Some of these genes also showed gender differences in correlation of gene expression level with Estrogen Receptor 2. To test if estrogens may drive these gender specific differences, we cultured EBV infected B cells (lymphoblastoid cell lines, LCLs), in medium depleted of serum to remove the effects of sex hormones as well as the estrogenic effect of phenol red, and then supplemented with estrogen (100 nM estradiol). Estradiol treatment altered MS risk gene expression, LCL proliferation rate, EBV DNA copy number and EBNA2 expression in a sex-dependent manner. Together, these data indicate that there are estrogen-mediated gender-specific differences in MS risk gene expression and EBV functions. This may in turn contribute to gender differences in host response to EBV and to MS susceptibility.

Background: Epstein-Barr virus (EBV) infection may be necessary for the development of Multiple sclerosis (MS). Earlier we had identified six MS risk loci that are co-located with binding sites for the EBV transcription factor Epstein-Barr Nuclear Antigen 2 (EBNA2) in EBV-infected B cells (lymphoblastoid cell lines – LCLs). Methods: We used an allele-specific chromatin immunoprecipitation PCR assay to assess EBNA2 allelic preference. We treated LCLs with a peptide inhibitor of EBNA2 (EBNA2-TAT), reasoning that inhibiting EBNA2 function would alter gene expression at these loci if it was mediated by EBNA2. Findings: We found that EBNA2 binding was dependent on the risk allele for five of these six MS risk loci (p < 0·05). Treatment with EBNA2-TAT significantly altered the expression of TRAF3 (p < 0·05), CD40 (p < 0·001), CLECL1 (p

The employment of chemical agents in the food industry is raising several concerns by consumers and is leading to an increasing interest in natural food preservatives. Among alternatives, host defense peptides (HDPs) have attracted great interest for their ability to preserve food samples from contamination without altering their quality, taste, and organoleptic properties. Recently, we evaluated the applicability of ApoB‐derived peptides as novel food bio‐preservatives and demonstrated their ability to prevent chicken meat sample contamination when immobilized on chitosan films. To perform a further step towards the applicability of these peptides in the food field, here we evaluated peptides biosafety and digestibility. To do this, we used a multidisciplinary approach including the evaluation of the peptides' toxicity and antimicrobial activity, the analysis of resistance phenotype development, an in silico prediction of the peptides' susceptibility to proteases and the evaluation of the peptides' stability in simulated gastric and intestinal fluids. ApoB‐derived peptides were found to be nontoxic when tested on human gastric carcinoma cells SNU‐1 and on human colon‐rectal adenocarcinoma cells HT‐29, and not to induce resistance phenotype in Salmonella strains. Bioinformatic analyses showed that the peptides are susceptible to several proteases, as also confirmed by experiments in simulated gastric and intestinal fluids. Altogether these findings open interesting perspectives to the future applicability of ApoB‐derived peptides as novel food biopreservatives. [ABSTRACT FROM AUTHOR]

Abstract Background Genome wide association studies have identified > 200 susceptibility loci accounting for much of the heritability of multiple sclerosis (MS). Epstein-Barr virus (EBV), a memory B cell tropic virus, has been identified as necessary but not sufficient for development of MS. The molecular and immunological basis for this has not been established. Infected B cell proliferation is driven by signalling through the EBV produced cell surface protein LMP1, a homologue of the MS risk gene CD40. Methods We have investigated transcriptomes of B cells and EBV-infected B cells at Latency III (LCLs) and identified MS risk genes with altered expression on infection and with expression levels associated with the MS risk genotype (LCLeQTLs). The association of LCLeQTL genomic burden with EBV phenotypes in vitro and in vivo was examined. The risk genotype effect on LCL proliferation with CD40 stimulation was assessed. Results These LCLeQTL MS risk SNP:gene pairs (47 identified) were over-represented in genes dysregulated between B and LCLs (p

Sepsis is associated with a dysregulated inflammatory response to infection. Despite the activation of inflammation, an immune suppression is often observed, predisposing patients to secondary infections. Therapies directed at restoration of immunity may be considered but should be guided by the immune status of the patients. In this paper, we described the use of a high-dimensional flow cytometry (HDCyto) panel to assess the immunophenotype of patients with sepsis. We then isolated peripheral blood mononuclear cells (PBMCs) from patients with septic shock and mimicked a secondary infection by stimulating PBMCs for 4 h in vitro with lipopolysaccharide (LPS) with or without prior exposure to either IFN-γ, or LAG-3Ig. We evaluated the response by means of flow cytometry and high-resolution clustering cum differential analysis and compared the results to PBMCs from healthy donors. We observed a heterogeneous immune response in septic patients and identified two major subgroups: one characterized by hypo-responsiveness (Hypo) and another one by hyper-responsiveness (Hyper). Hypo and Hyper groups showed significant differences in the production of cytokines/chemokine and surface human leukocyte antigen-DR (HLA-DR) expression in response to LPS stimulation, which were observed across all cell types. When pre-treated with either interferon gamma (IFN-γ) or lymphocyte-activation gene 3 (LAG)-3 recombinant fusion protein (LAG-3Ig) prior to LPS stimulation, cells from the Hypo group were shown to be more responsive to both immunostimulants than cells from the Hyper group. Our results demonstrate the importance of patient stratification based on their immune status prior to any immune therapies. Once sufficiently scaled, this approach may be useful for prescribing the right immune therapy for the right patient at the right time, the key to the success of any therapy.

Lambda interferons (IFN-λs) are a major component of the innate immune defense to viruses, bacteria, and fungi. In human liver, IFN-λ not only drives antiviral responses, but also promotes inflammation and fibrosis in viral and non-viral diseases. Here we demonstrate that macrophages are primary responders to IFN-λ, uniquely positioned to bridge the gap between IFN-λ producing cells and lymphocyte populations that are not intrinsically responsive to IFN-λ. While CD14+ monocytes do not express the IFN-λ receptor, IFNLR1, sensitivity is quickly gained upon differentiation to macrophages in vitro. IFN-λ stimulates macrophage cytotoxicity and phagocytosis as well as the secretion of pro-inflammatory cytokines and interferon stimulated genes that mediate immune cell chemotaxis and effector functions. In particular, IFN-λ induced CCR5 and CXCR3 chemokines, stimulating T and NK cell migration, as well as subsequent NK cell cytotoxicity. Using immunofluorescence and cell sorting techniques, we confirmed that human liver macrophages expressing CD14 and CD68 are highly responsive to IFN-λ ex vivo. Together, these data highlight a novel role for macrophages in shaping IFN-λ dependent immune responses both directly through pro-inflammatory activity and indirectly by recruiting and activating IFN-λ unresponsive lymphocytes.

Although the causes of Multiple Sclerosis (MS) still remain largely unknown, multiple lines of evidence suggest that Epstein–Barr virus (EBV) infection may contribute to the development of MS. Here, we aimed to identify the potential contribution of EBV-encoded and host cellular miRNAs to MS pathogenesis. We identified differentially expressed host miRNAs in EBV infected B cells (LCLs) and putative host/EBV miRNA interactions with MS risk loci. We estimated the genotype effect of MS risk loci on the identified putative miRNA:mRNA interactions in silico. We found that the protective allele of MS risk SNP rs4808760 reduces the expression of hsa-mir-3188-3p. In addition, our analysis suggests that hsa-let-7b-5p may interact with ZC3HAV1 differently in LCLs compared to B cells. In vitro assays indicated that the protective allele of MS risk SNP rs10271373 increases ZC3HAV1 expression in LCLs, but not in B cells. The higher expression for the protective allele in LCLs is consistent with increased IFN response via ZC3HAV1 and so decreased immune evasion by EBV. Taken together, this provides evidence that EBV infection dysregulates the B cell miRNA machinery, including MS risk miRNAs, which may contribute to MS pathogenesis via interaction with MS risk genes either directly or indirectly.

In this study, we examine patterns of students' literacy and engagement in science associated with different levels of "inquiry-oriented" learning reported by students in Australia, Canada, and New Zealand. To achieve this, we analyzed data from the Organisation for Economic Co-operation and Development's 2006 Programme for International Student Assessment, which had science as its focus. Consistently, our findings show that science students who report experiencing "low levels of inquiry-oriented learning activities" are found to have above-average levels of science literacy, but below-average levels of interest in science, and below-average levels on six variables that reflect students' engagement in science. Our findings show that the corollary is also true. Across the three countries, students who report "high levels of inquiry-oriented learning activities" in science are observed to have below-average levels of science literacy, but above-average levels of interest in learning science, and above-average engagement in science. These findings appear to run counter to science education orthodoxy that the more students experience inquiry-oriented teaching and learning, the more likely they are to have stronger science literacy, as well as more positive affect toward science. We discuss the implications of these findings for science educators and researchers.

Given international concerns about students' pursuit (or more correctly, non-pursuit) of courses and careers in science, technology, engineering and mathematics, this study is about achieving a better understanding of factors related to high school students' engagement in science. The study builds on previous secondary analyses of Programme for International Student Assessment (PISA) datasets for New Zealand and Australia. For the current study, we compared patterns of science engagement and science literacy for male and female students in Canada and Australia. The study's secondary analysis revealed that for all PISA measures included under the conceptual umbrella of "engagement in science" (i.e. interest, enjoyment, valuing, self-efficacy, self-concept and motivation), 15-year-old students in Australia lagged their Canadian counterparts to varying, albeit modest, degrees. Our retrospective analysis further shows, however, that gender equity in science engagement and science literacy is evident in both Canadian and Australian contexts. Additionally, and consistent with our previous findings for indigenous and non-indigenous students in New Zealand and Australia, we found that for male and female students in both countries, the factor most strongly associated with variations in engagement in science was the extent to which students participate in science activities outside of school. In contrast, and again for both Canadian and Australian students, the factors most strongly associated with science literacy were students' socioeconomic backgrounds, and the amount of formal time spent doing science. The implications of these results for science educators and researchers are discussed.

Access to clean drinking water is a major problem for many people across the world. Desalination is being increasingly used in many countries to provide this important resource. Desalination technology has received varying degrees of support in the communities in which this technology has been adopted. Productive communication suggests we understand the views of both "interested publics" and the views of water experts about these "interested publics". In this paper, we analyse the views of 16 water scientists involved in desalination research projects. We used a fourfold science communication typology to analyse scientists' discourse. While most participants expressed views which can be summarised as "We just need to educate the public," there are glimpses of more thoughtful approaches which could lead to more productive interaction between water experts and "interested publics".

Previous research has shown that indigenous students in Australia do not enjoy equal educational outcomes with other Australians. This secondary analysis of PISA 2006 confirmed that this continues to be the case in science literacy for secondary students. However, the analysis also revealed that indigenous Australian students held interest in science equal to that of their non-indigenous peers, and that observed variations in science literacy performance were most strongly explained by variations in reading literacy. These findings hold important implications for teachers, teacher educators, policy-makers, and researchers. Firstly, acknowledging and publicly valuing indigenous Australian science knowledge through rethinking school science curriculum seems an important approach to engaging indigenous students and improving their literacy in science. Secondly, appropriate professional learning for practising teachers and the incorporation of indigenous knowing in science methods training in teacher preparation seems warranted. Additionally, we offer a number of questions for further reflection and research that would benefit our understanding of ways forward in closing the science literacy gap for indigenous students. Whilst this research remains firmly situated within the Australian educational context, we at the same time believe that the findings and implications offered here hold value for science education practitioners and researchers in other countries with similar populations striving to achieve "science literacy for all". (Contains 2 figures and 2 tables.)

Public concerns about biotechnology have resulted in greater attention being paid to the mechanisms by which biotechnology is communicated with non-scientists, including the provision of science communication training. As undergraduate and postgraduate courses form the foundation of the biotechnology sector by providing a pipeline of university graduates entering into the profession, it has been proposed that formal science communication training be introduced at this early stage of career development. Using an Australian biotechnology degree course as a case study, this paper examines science communication training within this course and the views of past and present students towards this training. Interviews were undertaken with 22 stakeholders in the case, including undergraduate lecturers (who also supervise postgraduate research students), doctoral candidates and biotechnologists recently graduated from the course. Few of the students felt the course provided them with any form of science communication training, let alone training in how to engage non-scientists. Many were unaware of the training available to them and few of the lecturers were able to identify where communication skills are taught within the course. A previous study of this case has also shown that biotechnology undergraduates taking this course do not value communication with non-scientists. Clearly, the current state of science communication training for these students needs to be improved if they are to enter the biotechnology workforce as able "civic scientists." The findings of this study may be useful for other university biotechnology courses which have yet to integrate science communication training into their curriculum.

Despite rapid growth of the biotechnology industry worldwide, a number of public concerns about the application of biotechnology and its regulation remain. In response to these concerns, greater emphasis has been placed on promoting biotechnologists' public engagement. As tertiary science degree programmes form the foundation of the biotechnology sector by providing a pipeline of university graduates entering into the profession, it has been proposed that formal science communication training be introduced at this early stage of career development. The aim of the present study was to examine the views of biotechnology students towards science communication and science communication training. Using an Australian biotechnology degree programme as a case study, 69 undergraduates from all three years of the programme were administered a questionnaire that asked them to rank the importance of 12 components of a biotechnology curriculum, including two science communication items. The results were compared to the responses of 274 students enrolled in other science programmes. Additional questions were provided to the second year biotechnology undergraduates and semi-structured interviews were undertaken with 13 of these students to further examine their views of this area. The results of this study suggest that the biotechnology students surveyed do not value communication with non-scientists nor science communication training. The implications of these findings for the reform of undergraduate biotechnology courses yet to integrate science communication training into their science curriculum are discussed. (Contains 1 table and 3 figures.)

This paper reports on a completed field study that examined the usability and effectiveness of learning objects designed for Australian and New Zealand primary and secondary schools. It focuses on student engagement by observing the ways students interacted with learning objects and by listening to what they said about them. Questions that guided the field study included the following: Could the students use the learning objects easily? Did they enjoy the experience? Did they engage with the intended learning? These questions are examined with reference to students at different levels of schooling, and examples drawn from the fieldwork illustrate that, while some learning objects achieved their potential as engaging multimedia educational resources, others fell short. The paper provides a detailed examination of two learning objects to reveal what worked and what created barriers or subverted the intended learning. In particular, it explores interest, challenge and importance as elements that contributed to engagement and socially constructed learning.

Teachers have a central role in developing new learning models in schools. This paper describes a study that explored teachers' confidence and competence in using Information and Communication Technologies (ICT) as they participated in an ICT development project conducted by an Australian education system in 12 primary schools. The project aimed to develop ICT integrated teaching practices by providing in-class equipment and teacher professional development in ICT use, curriculum development and teaching strategies. The study used qualitative data from teacher records of Professional Development and Action Learning to identify three of four stages proposed to describe teachers' ICT learning. Teachers moved from gaining basic ICT skills, to conducting ICT-focused lessons and eventually appropriate ICT integration. Teachers who progressed to the third stage were able to exploit additional learning opportunities and begin to make fundamental changes to their pedagogy, but needed more time to reach the final stage of challenging existing pedagogical structures. (Contains 1 table and 1 figure.)

The Le@rning Federation, an agency funded by Australian and New Zealand governments, initiated a Field Review project as the start of a long-term research study to evaluate the impact, application and effectiveness of the online digital content developed according to the learning object model. In terms of content, the pilot Field Review found that many learning objects provided stimulating and diverse learning experiences for students. It is one of the potential strengths of learning objects that they are able to provide new geographical experiences and simulate dangerous or expensive learning activities at low relative cost.

A review is undertaken of what different commentators have written about the evaluation of educational courseware in higher education. Speculation is made on the reasons for the lack of such evaluations. The role of checklists for evaluating online courseware is discussed despite the acknowledged limitations. Checklists have been developed at Edith Cowan University specifically for assessing aspects of online pedagogical learning materials in higher education. These checklists are intended to be useful indicators of the areas where online learning materials are strong and identify areas that may be deficient rather than to arrive at a numeric score. The form of checklist proposed is a valuable screening device to use before undertaking a context-bound evaluation of courseware. Contextual evaluations are a complementary and valuable alternative to traditional forms of evaluation of educational courseware, such as checklists. A case is also made in this article for using a checklist developed for assessing aspects of online pedagogical learning materials in higher education. It is argued that, when used in conjunction with a context-bound approach, such checklists may be more useful in indicating the pedagogical quality of online learning materials. Quality of the instructional design remains an important consideration in evaluating courseware. Continuing comments and dissent are invited on the value of contextual evaluations of educational courseware to reinvigorate the debate over appropriate ways of evaluating online courseware that will provide helpful information for higher education.

Professional development (PD) for primary science teachers is recognized as an important activity which can support improved science education for students. Analysis of interviews with practicing primary science teachers is used to identify the range of PD experiences of a sample of teachers from Western Australia. Teachers' reasons for attending or avoiding science-related PD are categorized as "decision issues" which include opportunity, compulsion, convenience, enticement, interest, recommendation, and relevance. Case studies describe the interplay of these issues, which result in teachers' attendance or avoidance of PD. A subset of the sample is used to explore teachers' views of other activities which they recognize as contributing to their science teaching, content knowledge, and pedagogy. These other activities include hobbies, partner's job, and pursuing students' interests. Legitimating teachers' own interests as a source of personally derived PD is supported as an avenue to increase the diversity of topics studied by students and to increase the level of content knowledge held by teachers.

This study reports on the attitudes towards biotechnology of 905, 15-16 year-old students from 11 Western Australian schools. Students were asked to read 15 statements about biotechnology processes and to draw a line to separate what they considered "acceptable" statements from those they considered "unacceptable". Overall, the students hold a wide range of beliefs about what is an acceptable use of biotechnology. Their attitudes range from those of the 55 (6.0%) students who do not agree with the use of "any" living organisms in biotechnology to the 125 (14%) students who approve of "all" the stated uses of biotechnology, with a wide spread in between. Acceptance of the use of organisms in biotechnology decreases as we move from microorganisms (greater than 90% approval) to plants (71-82%) to humans (42-45%) and animals (34-40%). The attitudes of 99 students who recently studied biotechnology and have a good understanding of the processes and issues were similar in percentage and spread to those who were less informed. (Contains 1 table and 1 figure.)

Surveys (n=1116) 15-year-old students from 11 Western Australian schools to determine their understanding of and attitude towards recent advances in modern biotechnology. Discusses reasons for students' over-estimation of the use of biotechnology in society. Provides a rationale for the inclusion of biotechnology, a cutting edge science, in the school science curriculum. (Author/KHR)