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    An investigation into the cognitive ecology and electrophysiology of fungi and plants

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    The cognitive ecology of non-neural organisms like plants and fungi is a new and controversial research field that has gained momentum since the turn of the century. Many studies have suggested that plants and fungi perceive and respond plastically to their environment, implement behaviours that maximise their chances of survival, and that they have the ability to store memories, learn and communicate. However, little is known about how these phenomena occur and what underpins it. This is not only a scientific question, but also philosophical, with deep implications for what we understand by cognition. This thesis sought to contribute to this debate by focusing on the symbiotic relationship between mycorrhizal fungi and plants. After a general introduction situating the thesis in the epistemological debate and describing the challenge of establishing methods to study the cognitive ecology of plants and fungi in Chapter 1, Chapter 2 departs from the post-cognitivist tradition to build the hypothesis that the cognitive process of plants can be extended to that of mycorrhizal fungi when they are in symbiosis. Chapter 3 describes a failed attempt to test this hypothesis with the use of Perspex microcosms. Chapter 4 focused on the putative cognition of ectomycorrhizal fungi and how memory could be involved in its foraging behaviour, a hypothesis not supported by the evidence gathered during this study. Chapter 5 describes the successful attempt of using electrophysiological equipment to record the spontaneous and evoked electrical signalling of different fungal species, suggesting that this signalling could have the key to understand, in part, the complex and plastic behaviours these organisms present. The thesis concludes with Chapter 6, a rumination on the philosophical and practical challenges of both traditional and alternative views of cognition in non-neural organisms

    The role of isoquercetin, zafirlukast and its novel analogues for thiol isomerase inhibition in relation to thrombosis, cancer and other complications

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    Background: Thiol isomerases including PDI, ERp57, ERp72 and ERp5 play essential and distinct roles in thrombosis, cancer progression, cancer cell signalling and metastasis. Thiol isomerase inhibitors constitute a class of agents to combat these complications where they generally have been studied to combat either thrombosis or cancer but not both. Recently, our lab has identified the FDA approved leukotriene receptor antagonist, zafirlukast, as a broad-spectrum thiol isomerase inhibitor able to inhibit platelet aggregation and thrombus formation. Aims: The aims of this thesis begin with the goal to improve the efficacy of zafirlukast for thrombotic inhibition via the exploration of zafirlukast analogues. It continues by exploring how zafirlukast fairs against and ovarian cancer model, and whether its effects can be improved by combining it with a standard chemotherapy regimen or with another thiol isomerase inhibitor, isoquercetin. It concludes by exploring the mechanistic effects of thiol isomerase inhibition, and pathways affected through zafirlukast and isoquercetin treatment. Results: One of 35 zafirlukast analogues, termed compound 21, demonstrated greater potency than zafirlukast and was able to better inhibit platelet aggregation, P-selectin exposure and thrombus formation. Both zafirlukast and compound 21 demonstrated reversibility of thiol isomerase inhibition and demonstrated no cytotoxicity towards cultured lung liver and kidney cells. Although compound 21 was a better inhibitor overall, it only held a 2.5-fold increase in potency, so to explore the effects of zafirlukast on cancer inhibition I remained with the parent compound, which demonstrated inhibition of cancer growth in an ovarian xenograft model. With this data we performed a pilot clinical trial of zafirlukast’s anticancer effects in ovarian cancer patients. These results however were inconclusive; therefore, I tried improving the efficacy of zafirlukast by combining it with isoquercetin or cisplatin/gemcitabine. When combined with isoquercetin in low doses the effects were similar to that of a high dose of zafirlukast on its own. Then when zafirlukast was combined with cisplatin/gemcitabine a greater inhibition was seen than just the chemotherapy on its own. Finally, in addition to inhibiting thiol isomerases zafirlukast and isoquercetin were able to inhibit factors involved in cancer induced thrombosis, angiogenesis and inflammation including tissue factor, VEGF, TMEM176B and PD-L1. Conclusions: One conclusion drawn from this thesis is that thiol isomerase inhibitors, such as zafirlukast, are able to act as both anti-thrombotic and anti-cancer agents, making zafirlukast an interesting drug to continue exploring in combination with chemotherapeutic drugs to potentially combat cancer induced thrombosis. Another conclusion is that it is possible to alter zafirlukast to perform better as an inhibitor, where it can continue to be explored for even better analogue development. Additionally, zafirlukast in combination with another thiol isomerase inhibitor, such as isoquercetin can also improve efficacy and target other pathways beyond thiol isomerases

    The Haiti Cholera claims: from symbolic to material reparations

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    In this essay, we will use the Haiti Cholera case study to explore how the victims and the socioeconomic turns are increasingly pivotal in the field of reparations as part of transitional justice. On December 1, 2016, UN Secretary General Ban Ki-moon apologized for the cholera epidemic in Haiti, an illness which arrived with Nepalese peacekeepers deployed after the 2010 earthquake. After years of silence and denial from the UN, the UN finally established a “New Approach to Cholera in Haiti,” promising material assistance and support to the victims through a “victim-centered approach.” The essay builds on our previous matrix used to clarify the debate made of two separate dimensions: the focus of reparations—collective versus individual—and the means of reparations—symbolic versus material.1 Based on fieldwork conducted in March 2017 in the communities most affected by the cholera outbreak, we demonstrate how the tensions between reparations offered by the UN (with a preference for collective symbolic reparations) and the reparations demanded by the victims (individual material reparations) can help explain why reparations were not fully (at best) successful in providing justice for the Haiti cholera victims and hopefully inform practice in this area for other UN trust funds and victims’ rights mechanisms. The first section discusses the specifics of the cholera crisis in Haiti and the subsequent Haiti Cholera Claims, including the sudden change of position by the UN in 2016 and the nature of reparations included in the New Approach to Cholera in Haiti. The second section looks at the reparations debate and the preferences expressed by the affected communities in Haiti. The third section puts the Haiti Cholera Claims in perspective, discussing the Kosovo Lead Poisoning case and the Mothers of Srebrenica case, both third party cases involving a UN peacekeeping presence like the Haiti Cholera Claims. Finally, the last section looks at the ramifications of the Haiti Cholera Claims and how reparations debates need to take into account wider structural factors impacting the development of third world countries

    The effect of Vitamin B6 supplementation on anxiety-related behaviour, sensorimotor function, and cortical neuronal activity in healthy adult rats

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    This doctoral thesis presented two studies. The first study focuses on the effect of Vitamin B6 (VitB6) supplementation, and the second study examines the phase relationship of local field potentials (LFPs) between the barrel and motor cortices. The same rodent model was employed in both studies. VitB6 is an essential water-soluble vitamin involved in amino acid metabolism, neurotransmitter synthesis, and neuronal function. While its deficiency is well-documented to impair neurological and cognitive processes, the effect of VitB6 supplementation on anxiety-related behaviour and sensorimotor function, and cortical neuronal activity in neurotypical populations has attracted interest in recent years due to the increasing number of diagnosed anxiety disorders globally. The work presented here used a cohort of young male adult Lister Hooded rats not deficient in VitB6. They were randomly assigned to a control and a VitB6 supplemented group. The VitB6 group were supplemented with ViB6 at 40 times the recommended dietary allowance (RDA) via drinking water for 5 weeks, with the control group for comparison. The open field test was used to assess anxiety-like behaviour, and rotarod tasks for motor coordination, while concurrent electrophysiological recordings from the barrel and motor cortices were used to evaluate neural activity. Serum VitB6 levels, dietary intake, and physiological parameters were also monitored. Our results indicated that VitB6-supplemented rats showed significantly reduced anxiety-like behaviour (fewer faecal boli and increased centre exploration in the open field) and exhibited enhanced sensorimotor performance (longer latency to fall on the rotarod) compared to control rats. However, no significant difference was detected in the neural activity of the barrel cortex between the groups in terms of the evoked local field potential (LFP), multi-unit activity (MUA), sensory adaptation, as well as resting state neural signals. As to the cortico-cortical phase relationship between the barrel and motor cortices, our results revealed that under whisker pad stimulation, the evoked neural response in the barrel cortex preceded that in the motor cortex, as expected. However, during resting state under the condition of slow wave oscillation (SWO), the Up state initiation was earlier in the motor cortex compared to the barrel cortex but returned to the baseline later, indicating a prolonged Up state phase in the motor cortex relative to the barrel cortex. Consistent with the earlier onset of Up states, the onset of burst during resting state of burst suppression in the motor cortex also preceded the barrel cortex. We further showed that these phase relationships between the barrel and motor cortices were not significantly different between the control and VitB6 groups. Our findings suggest that VitB6 supplementation may have positive outcomes in reducing anxiety and enhancing motor coordination even in healthy individuals, offering potential benefits for improving mental health and healthy living for the general population. However these behavioural differences didn’t result in significant differences between the control and VitB6 groups in terms of neural activities in the barrel cortex under whisker pad stimulation or resting state. Our study also provided new insights into neocortical communication and introduced a novel approach to investigate cortico-cortical network dynamics

    Seeing conflict: identifying self-control conflict attenuates early allocation of visual attention to positive stimuli

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    Positive information such as temptations or stimuli related to reward attracts attention. This attentional bias is often considered to be habit-like and, consequently, to contribute to self-control problems. In contrast, we document across three studies how attention allocation to positive stimuli is attenuated when observers identify a conflict between positive information and a more important current goal. In Study 1, students attended away from leisure-related temptations in the presence of studying reminders, however, they paid more attention to such positive, tempting stimuli when conflict was less salient such as when planning to engage in more leisure activities. Study 2 and 3 manipulated experimentally whether a conflict is identified and tested the effects of conflict identification on attention allocation. In study 2, students attended away from a positive temptation when they were prompted to consider it as detrimental to their studying goals but not when they reflected on how it might support their studying goals. This supports our assumption that activating a more important goal by itself does not cause attenuation of attention but the identification of a conflict with a goal. In study 3, reward-related information was attended to, but attention was attenuated when participants were instructed that the stimuli would temporarily harm and thus be in conflict with a more important goal. This effect was visible even without allowing participants to forget about the association with reward. In sum, malleable perceptions of conflict between positive information and important goals shape how observers orient to such information

    Deciphering landscape‐scale plant cover and biodiversity from soil eDNA

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    Biodiversity surveys are critical for detecting environmental change; however, undertaking them at scale and capturing all available diversity through observation is challenging and costly. This study evaluated the potential of soil‐extracted eDNA to describe plant communities and compared these findings to traditional, observation‐based field surveys. We analyzed 789 soil samples using high‐throughput amplicon sequencing and compared DNA‐based diversity metrics, indicator taxa, predicted vegetation class, and plant cover in a comparison with co‐located field survey data. The results indicated that taxonomically aggregated (genus) eDNA‐derived data, while showing slightly reduced Shannon's diversity scores, yielded remarkably similar overall richness and composition estimates. However, the DNA indicator taxa and predictive power for vegetation community classification were also lower overall than those recorded by the field survey. In many cases, plant cover could be inferred from amplicon abundance data with some accuracy despite widely differing scales of sampling—0.25 g crumb of soil versus a 1 m2 quadrat. Overall, results from eDNA demonstrated lower sensitivity but were broadly in accordance with traditional surveys, with our findings revealing comparable taxonomic resolution at the genus level. We demonstrate the potential and limitations of a simple molecular method to inform landscape‐scale plant biodiversity surveys, a vital tool in the monitoring of land use and environmental change

    The impact of probiotic live yeast in a barley grain-based diet on rumen microbial communities, fermentation, and histology of artificially reared lambs

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    This study aimed to investigate the effect of dietary supplementation with a probiotic live yeast Saccharomyces cerevisiae on rumen microbial communities, enzymatic activities, volatile fatty acid concentrations, and histology in artificially reared lambs fed a diet rich in fermentable carbohydrates. After colostrum administration, forty-two Chios lambs were divided into two homogenous groups (n = 21); the control (C) and probiotic supplemented group (P) and were artificially reared until the 45th day (d) of age. From the 30th until the 106th d of lambs’ age, both groups were fed alfalfa hay and barley grain-based concentrate mix ad libitum. Moreover, 100 g of concentrate including 0.1 g of Saccharomyces cerevisiae CNCM I-1077 live yeast (1010 CFU/g) was offered to P lambs to ensure a constant intake of the yeast. Although no difference was evident for the alpha-diversity, several interesting features were found for beta-diversity. Butyrivibrio, Pseudobutyrivibrio, and acetate producer Sphaerochaeta were significantly more abundant (P = 0.029, P = 0.029 and P = 0.008, respectively) in P- compared to C-fed lambs at 100 d, while population of lactate users were varying significantly in P- and C- fed lambs at 100 d [higher abundance of Megasphaera in C- (P = 0.001) and Anaerovibrio in P-fed lambs (P = 0.046), respectively]. Acidaminococcaceae and Clostridia UCG-014 were found in a lower abundance (P = 0.059 and P = 0.008, respectively) in P- compared to C-fed lambs at 100 d. Both ruminal pH and the activities of fibrolytic enzymes did not differ amongst the dietary treatments, while total volatile fatty acid concentrations were increased (P < 0.001) in P- compared to C-fed lambs at 100 d. As regards the serosa, the muscular layers, the intramural vasculature and innervation, our results showed no effect in rumen histology due to the dietary treatment, however, changes were evident in the mucosa where all constituent layers of the epithelium presented distinctly and with similar thickness, especially around papillae, the collagen and reticular fibers were more densely and evenly packed, and prekeratins and keratins delineated more distinctly epithelial pegs in P-fed when compared to C-fed lambs. The inclusion of live yeast S. cerevisiae CNCM I-1077 promoted rumen microbiota stability and limited extensive keratinization of the epithelium due to a highly fermentable carbohydrate diet formulation

    A systematic review of the factors affecting textural perception by older adults and their association with food choice and intake

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    Eating behaviours among older adults can be affected by age-associated oral physiological changes. This may influence nutritional intake, liking and acceptance of foods, increasing malnutrition risk. To better understand age-associated changes to textural perception, a systematic review was designed to evaluate the factors that affect the perception of food texture among older adults, and the impact this has on food liking and intake. Electronic searches were conducted in three databases (Pubmed, WebofScience, Scopus), yielding 12,216 articles. The 2020 PRISMA guidelines were used to screen all articles; these were assessed in three stages, by title, abstract and full text. Subsequently, PECO (population, exposure, comparison, outcome) guidelines were applied to assess study eligibility. 13 articles were included in the final review, all of which were of sufficient quality. A wide range of methodologies and outcomes were identified, leading to the discussion of findings in three categories; (i) oral manipulation and processing of food types within the oral cavity, (ii) age-associated changes to the physical properties of this cavity, and (iii) psychological factors that influence food choice and acceptance. A combination of these factors facilitate textural manipulation and perception in older adults, which were shown to significantly drive product acceptance and intake. Whereas several perceptual and physiological changes that occur with aging are unavoidable, recognising the heterogenous nature of older adults will lead to a better understanding of the oral capabilities and sensory-specific needs of this population, and could be used to improve food acceptance, nutritional intake and reduce the risk of malnutrition

    Women’s greater participation in agriculture: implications for energy expenditure, time use, and nutrition from a case study in Telangana, India

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    Several aspects of rural transformation in LMICs call for greater participation by women in agriculture. However, empirical evidence does not show a clear link between greater participation by women in agriculture and improved nutritional status. This paper examines two key nutrition impact pathways – changes in energy demands and time-use patterns due to increased participation in agriculture. The study is based on data collected from rural agricultural households across agricultural seasons in Adilabad District, Telangana State, India. A novel aspect of the study is the use of accelerometers for energy expenditure assessments. Our findings show that increased participation by women in agriculture leads only to modest rises in energy demand and physical activity levels, as agricultural tasks are not much more energy-intensive than the domestic/care activities they replace. Increased energy expenditure due to more time spent on agricultural activities is generally offset by higher calorie intake, with no significant impacts on calorie adequacy. However, increased participation in agriculture significantly changes women’s time-use patterns, reducing time for domestic work, leisure, and care, which may affect nutrition and wellbeing. Impacts on nutrition and wellbeing are more likely to arise from changes in time-use patterns than from increased energy demands of agricultural work

    Attacking drug cartels in the territory of another State

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