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In vivo imaging of astrocytes in the whole brain with engineered AAVs and diffusion-weighted magnetic resonance imaging
Get PDFAstrocytes constitute a major part of the central nervous system and the delineation of their activity patterns is conducive to a better understanding of brain network dynamics. This study aimed to develop a magnetic resonance imaging (MRI)-based method in order to monitor the brain-wide or region-specific astrocytes in live animals. Adeno-associated virus (AAVs) vectors carrying the human glial fibrillary acidic protein (GFAP) promoter driving the EGFP-AQP1 (Aquaporin-1, an MRI reporter) fusion gene were employed. The following steps were included: constructing recombinant AAV vectors for astrocyte-specific expression, detecting MRI reporters in cell culture, brain regions, or whole brain following cell transduction, stereotactic injection, or tail vein injection. The astrocytes were detected by both fluorescent imaging and Diffusion-weighted MRI. The novel AAV mutation (Site-directed mutagenesis of surface-exposed tyrosine (Y) residues on the AAV5 capsid) significantly increased fluorescence intensity (p < 0.01) compared with the AAV5 wild type. Transduction of the rAAV2/5 carrying AQP1 induced the titer-dependent changes in MRI contrast in cell cultures (p < 0.05) and caudate-putamen (CPu) in the brain (p < 0.05). Furthermore, the MRI revealed a good brain-wide alignment between AQP1 levels and ADC signals, which increased over time in most of the transduced brain regions. In addition, the rAAV2/PHP.eB serotype efficiently introduced AOP1 expression in the whole brain via tail vein injection. This study provides an MRI-based approach to detect dynamic changes in astrocytes in live animals. The novel in vivo tool could help us to understand the complexity of neuronal and glial networks in different pathophysiological conditions
But, who is the victim here? Exploring judgments toward hypothetical bidirectional domestic violence scenarios
Get PDFGendered models of abuse describe intimate partner violence (IPV) as unilaterally perpetrated by dominant, aggressive men towards vulnerable women. This unidirectional conceptualization has contributed to a “domestic violence stereotype” which, alongside broader attitudes regarding gender, influences attitudes towards ‘non-typical’ victim and perpetrator groups (e.g., male victims, female perpetrators, those within same-sex relationships), and has significant outcomes for help-seeking decision-making, as well as responses from service providers and the criminal justice system. Whilst prevalence data and research suggest bidirectional violence is in fact the most common pattern (e.g., see Langhinrichsen-Rohling, Misra, Selwyn, & Rohling, 2012), there is still little known about how the stereotypes and attitudes described above manifest in scenarios where both parties occupy ‘victim’ and ‘perpetrator’ labels. The present pilot study therefore asked 178 undergraduate students to allocate ‘victim’ and ‘perpetrator’ labels, and make judgments of severity, resolution and justice outcomes, towards hypothetical opposite-sex IPV scenarios varying on the proportion of abuse perpetrated by each party, and type of violence. Results showed that participants were reluctant to label men as ‘victims’, and women as ‘perpetrators’, across scenarios. They were also less likely to recommend that the man should call the police. These exploratory results therefore suggest that powerful stereotypes about IPV and gender may serve to influence perceptions of bidirectional violence and point to a need to study this issue in more detail in order to elucidate the most appropriate way to begin to address these issues
Downstream of the HOX genes: explaining conflicting tumour suppressor and oncogenic functions in cancer
Get PDFThe HOX genes are a highly conserved group of transcription factors that have key roles in early development, but which are also highly expressed in most cancers. Many studies have found strong associative relationships between the expression of individual HOX genes in tumours and clinical parameters including survival. For the majority of HOX genes, high tumour expression levels seem to be associated with a worse outcome for patients, and in some cases this has been shown to result from the activation of pro-oncogenic genes and pathways. However, there are also many studies that indicate a tumour suppressor role for some HOX genes, sometimes with conclusions that contradict earlier work. In this review, we have attempted to clarify the role of HOX genes in cancer by focusing on their downstream targets as identified in studies that provide experimental evidence for their activation or repression. On this basis, the majority of HOX genes would appear to have a pro-oncogenic function, with the notable exception of HOXD10, which acts exclusively as a tumour suppressor. HOX proteins regulate a wide range of target genes involved in metastasis, cell death, proliferation, and angiogenesis, and activate key cell signalling pathways. Furthermore, for some functionally related targets, this regulation is achieved by a relatively small subgroup of HOX genes
How do Education doctoral students understand university teaching?
No full textDoctoral students often take teaching roles in their universities – what do these students believe about good practice in the sector and how can they be supported
An efficient design of primary sedimentation tanks using a combination of the response surface, metaheuristic, and scenario building methods
Get PDFSolid particle sedimentation is assumed to be a complex procedure in water and wastewater treatment plants. There is great interest in applying and developing different simulation and optimization methods to design primary sedimentation tanks (PSTs). In traditional techniques, mechanical and physical parameters are set by sequential error loops. This study proposes a hybrid method based on the response surface methodology, efficient metaheuristics, and scenario building methods using different experimental methods to eliminate the disadvantage of existing techniques. This novel framework creates a robust and sustainable design for the PSTs. First of all, the parameters of the considered PST, based on the economic, improve process and tank efficiency scenarios are tuned and optimized by the central composition design and response surface methodology. To forecast an efficient response value for these scenarios, different metaheuristic algorithms, including the genetic algorithm (GA), pattern search algorithm (PSA), and simulate annealing algorithm, are applied. Results demonstrated that PSA, GA, and PSA with 0.02, 0.032, and 0.063 compared to experimental practices have the best calibration for predicting response in economic, improved process and tank efficiency scenarios, correspondingly. Finally, experimental tests have proven that the optimum Retention Time is equal to 2 h based on the biological oxygen demand and the total suspended solids eliminations in the laboratory-scale setup
Glucosyltransferase-dependent and independent effects of Clostridioides difficile toxins during infection
Get PDFClostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea and pseudomembranous colitis in the USA. In addition to these symptoms, patients with CDI can develop severe inflammation and tissue damage, resulting in life-threatening toxic megacolon. CDI is mediated by two large homologous protein toxins, TcdA and TcdB, that bind and hijack receptors to enter host cells where they use glucosyltransferase (GT) enzymes to inactivate Rho family GTPases. GT-dependent intoxication elicits cytopathic changes, cytokine production, and apoptosis. At higher concentrations TcdB induces GT-independent necrosis in cells and tissue by stimulating production of reactive oxygen species via recruitment of the NADPH oxidase complex. Although GT-independent necrosis has been observed in vitro, the relevance of this mechanism during CDI has remained an outstanding question in the field. In this study we generated novel C. difficile toxin mutants in the hypervirulent BI/NAP1/PCR-ribotype 027 R20291 strain to test the hypothesis that GT-independent epithelial damage occurs during CDI. Using the mouse model of CDI, we observed that epithelial damage occurs through a GT-independent process that does not involve immune cell influx. The GT-activity of either toxin was sufficient to cause severe edema and inflammation, yet GT activity of both toxins was necessary to produce severe watery diarrhea. These results demonstrate that both TcdA and TcdB contribute to disease pathogenesis when present. Further, while inactivating GT activity of C. difficile toxins may suppress diarrhea and deleterious GT-dependent immune responses, the potential of severe GT-independent epithelial damage merits consideration when developing toxin-based therapeutics against CDI
Introduction to this special section: engineering geophysics
Get PDFIn the context of our growing population, new paradigms are required for, e.g., the monitoring and management of infrastructure and buildings and the use of the subsurface and its resources. Increasing energy demands entail continuous improvement of imaging techniques to better understand subsurface resources and to maximize production in an environmentally safe manner. Climate change, in combination with rapid population growth, puts increasing pressure on freshwater resources, groundwater systems, and urban living environments. Many subdisciplines and areas within geophysics, including engineering geophysics, are increasingly involved in tackling these global challenges
Indoor air quality (IAQ) evaluation of higher education learning environments
Get PDFIndoor Air Quality (IAQ), particularly in educational facilities, is gaining considerable interest and is a synonymous indicator towards evaluating human comfort. Factors such as CO2 concentration, temperature, and humidity play crucial parts in determining an acceptable level of IAQ. Many studies have also demonstrated that the indoor air quality of classrooms affects students’ concentration and performance. Today with the threat of a global pandemic, the demand of clean & fresh indoor air quality in education buildings is extremely intensive. This study focuses on investigating IAQ situations and changes in different typical functional spaces of a higher education building in the UK. CO2, temperature, and humidity data in various learning environment were monitored via data loggers during the winter. Associated with data monitoring, a set of questionnaires surveys were carried out to evaluate the user’s experience. The results of this study show that temperature and CO2 concentration in the classrooms was constantly higher than the government guidance on a daily basis. The analysis also shows that temperature and humidity increased with CO2 levels, but at a much lower rate. This study has revealed poor and concerning IAQ in higher education buildings in the UK, particularly in larger rooms with high occupancy. Along with the findings, this paper also identifies possible impact or factors and proposes solutions to overcome these issues
Sustainability based careers and graduate prospects
Get PDFThe United Nations Sustainable Development Goals aim to create a sustainable global future through seventeen inter-related objectives that encompass the environment, social justice, and good governance. Countries are deploying national programmes to meet their sustainable development targets. Sustainability-based career roles are being created at a rate faster than employers can fill them. Recent evidence suggests that employment in sustainability sectors and related professions can provide more favourable opportunities for graduates seeking their first job. Universities are also called upon to do more about sustainability. They are increasingly coming under scrutiny from students as to their sustainability performance. Embedding sustainability in the curriculum and linking it to employability is needed to ensure the relevance of higher education to students and employers. Educators must also consider the efficacy of their pedagogy in teaching sustainability
Animal-based vs plant-based protein quality. A survey of millennial students nutritional knowledge and food preferences
Get PDFThe food system around the mass production of meat and by-products constitutes a major driver of global warming, diminution of Earth’s resources, land degradation and deforestation, as well as contamination of aquatic and terrestrial ecosystems (IPCC, 2019; UN Environment Programme, 2018). At its current levels, worldwide food consumption practices are high, and particularly so in meat products. Proof lies in the environmental data, which is swiftly accumulating on the unsustainability of meat (Sabaté et al., 2014).
At the present day, meat production is accountable for occupying over half of the Earth’s cultivable land resources and for driving greenhouse gas emissions. Supporting those findings is Eshel’s research (2014), which found that meat eaters employ over 160 percent of land resources when compared to those people who are reliant on a plant-based diet. In fact, although varying across several crop categories and regions, the global average water footprint related to crop production is remarkably lower when compared to the effect of meat production over freshwater sources (Mekonnen et al., 2012).
Meat production necessitates around 2422 Gm3 of water per year, the provision of just 1 kg of animal protein demands almost 100 times more water than producing 1 kg of grain protein (Lonnie and Johnstone, 2020). As a result, only a mitigated, global shift in dietary changes that are mainly reliant on nutritionally balanced, plant-based sourced of protein could sustainably feed 10 billion people by 2050. This would guarantee nutritional adequacy, food security and food sufficiency (LEAP, 2020; Willet et al., 2019). According to the European Environment Agency (2019) there are increasing concerns related to the linkage between an excessive consumption of animal-derived proteins and issues related to health and environment. Within this context, 1 in 5 people living in the UK have already stopped or reduced their meat consumption (The Vegan Society, 2020).
Currently, there is increased awareness, particularly popular within millennials, regarding the adoption of a healthy, balanced diet which includes plant-based sources of protein. A conscious consumerism is in fact driving the trend towards the consumption of novelty food, more particularly plant-based, protein-rich products. In fact, according to data collected by Proveg Int. (2019) the UK's purchase and consumption rates of vegan products, more specifically milk, meat, margarine, cheese, readymade meals, and seafood, are amongst the highest in Europe. Within this frame of perpetual development, consumers are looking beyond the label. Eager to experiment with the inclusion of a wider variety of food options into their diet, their interest in converting and expanding their palate is increasing and subject to a continuous evolution (Mintel, 2018).
What used to appeal to a niche sector, is guaranteed to have a prosperous future within the food and beverage industry. In fact, vegans and vegetarians is projected to be a quarter of the British population by 2025, and flexitarians just under half of all UK consumers (Sainsbury’s, 2019). Despite the increase in the number of people switching to a plant-based diet, meat consumption remains highly ingrained in Western culture and the disposition to stop or reduce consumption of animal products therefore remains relatively low. Consumers often describe plant-based products to have unappealing taste, texture, and appearance. Meat substitutes are difficult to find, often highly priced and more challenging to cook than their meat counterparts (Forbes, 2019; Mintel, 2020).
The lack of a wide array of studies conducted on the subject might be due to the concept of protein quality that remains a “grey area”. The consumption of proteins-enriched products is nothing but a relatively recent trend. The significance of this research ties back to the fact that there is a limited amount of evidence and literature related to familiarity with the concept of protein content and perceptions related to healthfulness and wellbeing. More importantly, no past research has taken into consideration millennial university students.
This study aims to assess millennial university students’ nutritional knowledge and preferences related to food regimes, with a particular insight on the protein quality content of food, which focuses and distinguishes mainly between plant-based and animal-based protein sources