9,573 research outputs found

    Bioactive Compounds from Marine Heterobranchs

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    The natural products of heterobranch molluscs display a huge variability both in structure and in their bioactivity. Despite the considerable lack of information, it can be observed from the recent literature that this group of animals possesses an astonishing arsenal of molecules from different origins that provide the molluscs with potent chemicals that are ecologically and pharmacologically relevant. In this review, we analyze the bioactivity of more than 450 compounds from ca. 400 species of heterobranch molluscs that are useful for the snails to protect themselves in different ways and/or that may be useful to us because of their pharmacological activities. Their ecological activities include predator avoidance, toxicity, antimicrobials, antifouling, trail-following and alarm pheromones, sunscreens and UV protection, tissue regeneration, and others. The most studied ecological activity is predation avoidance, followed by toxicity. Their pharmacological activities consist of cytotoxicity and antitumoral activity; antibiotic, antiparasitic, antiviral, and anti-inflammatory activity; and activity against neurodegenerative diseases and others. The most studied pharmacological activities are cytotoxicity and anticancer activities, followed by antibiotic activity. Overall, it can be observed that heterobranch molluscs are extremely interesting in regard to the study of marine natural products in terms of both chemical ecology and biotechnology studies, providing many leads for further detailed research in these fields in the near future

    Statistical Learning for Gene Expression Biomarker Detection in Neurodegenerative Diseases

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    In this work, statistical learning approaches are used to detect biomarkers for neurodegenerative diseases (NDs). NDs are becoming increasingly prevalent as populations age, making understanding of disease and identification of biomarkers progressively important for facilitating early diagnosis and the screening of individuals for clinical trials. Advancements in gene expression profiling has enabled the exploration of disease biomarkers at an unprecedented scale. The work presented here demonstrates the value of gene expression data in understanding the underlying processes and detection of biomarkers of NDs. The value of novel approaches to previously collected -omics data is shown and it is demonstrated that new therapeutic targets can be identified. Additionally, the importance of meta-analysis to improve power of multiple small studies is demonstrated. The value of blood transcriptomics data is shown in applications to researching NDs to understand underlying processes using network analysis and a novel hub detection method. Finally, after demonstrating the value of blood gene expression data for investigating NDs, a combination of feature selection and classification algorithms were used to identify novel accurate biomarker signatures for the diagnosis and prognosis of Parkinson’s disease (PD) and Alzheimer’s disease (AD). Additionally, the use of feature pools based on previous knowledge of disease and the viability of neural networks in dimensionality reduction and biomarker detection is demonstrated and discussed. In summary, gene expression data is shown to be valuable for the investigation of ND and novel gene biomarker signatures for the diagnosis and prognosis of PD and AD

    Examining the Impact of Personal Social Media Use at Work on Workplace Outcomes

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    A noticable shift is underway in today’s multi-generational workforce. As younger employees propel digital workforce transformation and embrace technology adoption in the workplace, organisations need to show they are forward-thinking in their digital transformation strategies, and the emergent integration of social media in organisations is reshaping internal communication strategies, in a bid to improve corporate reputations and foster employee engagement. However, the impact of personal social media use on psychological and behavioural workplace outcomes is still debatebale with contrasting results in the literature identifying both positive and negative effects on workplace outcomes among organisational employees. This study seeks to examine this debate through the lens of social capital theory and study personal social media use at work using distinct variables of social use, cognitive use, and hedonic use. A quantitative analysis of data from 419 organisational employees in Jordan using SEM-PLS reveals that personal social media use at work is a double-edged sword as its impact differs by usage types. First, the social use of personal social media at work reduces job burnout, turnover intention, presenteeism, and absenteeism; it also increases job involvement and organisational citizen behaviour. Second, the cognitive use of personal social media at work increases job involvement, organisational citizen behaviour, employee adaptability, and decreases presenteeism and absenteeism; it also increases job burnout and turnover intention. Finally, the hedonic use of personal social media at work carries only negative effects by increasing job burnout and turnover intention. This study contributes to managerial understanding by showing the impact of different types of personal social media usage and recommends that organisations not limit employee access to personal social media within work time, but rather focus on raising awareness of the negative effects of excessive usage on employee well-being and encourage low to moderate use of personal social media at work and other personal and work-related online interaction associated with positive workplace outcomes. It also clarifies the need for further research in regions such as the Middle East with distinct cultural and socio-economic contexts

    Unraveling the effect of sex on human genetic architecture

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    Sex is arguably the most important differentiating characteristic in most mammalian species, separating populations into different groups, with varying behaviors, morphologies, and physiologies based on their complement of sex chromosomes, amongst other factors. In humans, despite males and females sharing nearly identical genomes, there are differences between the sexes in complex traits and in the risk of a wide array of diseases. Sex provides the genome with a distinct hormonal milieu, differential gene expression, and environmental pressures arising from gender societal roles. This thus poses the possibility of observing gene by sex (GxS) interactions between the sexes that may contribute to some of the phenotypic differences observed. In recent years, there has been growing evidence of GxS, with common genetic variation presenting different effects on males and females. These studies have however been limited in regards to the number of traits studied and/or statistical power. Understanding sex differences in genetic architecture is of great importance as this could lead to improved understanding of potential differences in underlying biological pathways and disease etiology between the sexes and in turn help inform personalised treatments and precision medicine. In this thesis we provide insights into both the scope and mechanism of GxS across the genome of circa 450,000 individuals of European ancestry and 530 complex traits in the UK Biobank. We found small yet widespread differences in genetic architecture across traits through the calculation of sex-specific heritability, genetic correlations, and sex-stratified genome-wide association studies (GWAS). We further investigated whether sex-agnostic (non-stratified) efforts could potentially be missing information of interest, including sex-specific trait-relevant loci and increased phenotype prediction accuracies. Finally, we studied the potential functional role of sex differences in genetic architecture through sex biased expression quantitative trait loci (eQTL) and gene-level analyses. Overall, this study marks a broad examination of the genetics of sex differences. Our findings parallel previous reports, suggesting the presence of sexual genetic heterogeneity across complex traits of generally modest magnitude. Furthermore, our results suggest the need to consider sex-stratified analyses in future studies in order to shed light into possible sex-specific molecular mechanisms

    Cis-Regulation of Gremlin1 Expression during Mouse Limb Bud Development and its Diversification during Vertebrate Evolution

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    Embryonic development and organogenesis rely on tightly controlled gene expression, which is achieved by cis-regulatory modules (CRMs) interacting with distinct transcription factors (TFs) that control spatio-temporal and tissue-specific gene expression. During organogenesis, gene regulatory networks (GRNs) with selfregulatory feedback properties coordinately control growth and patterning and provide systemic robustness against genetic and/or environmental perturbations. During limb bud development, various interlinked GRNs control outgrowth and patterning along all three limb axes. A paradigm network is the epithelial-mesenchymal (e-m) SHH/GREM1/AER-FGF feedback signaling system which controls limb bud outgrowth and digit patterning. The BMP antagonist GREMLIN1 (GREM1) is central to this e-m interactions as its antagonism of BMP activity is essential to maintain both AER-Fgf and Shh expression. In turn, SHH signaling upregulates Grem1 expression, which results in establishment of a self-regulatory signaling network. One previous study provided evidence that several CRMs could regulate Grem1 expression during limb bud development. However, the cis-regulatory logics underlying the spatio-temporal regulation of the Grem1 expression dynamics remained obscure. From an evolutionary point of view, diversification of CRMs can result in diversification of gene regulation which can drive the establishment of morphological novelties and adaptions. This was evidenced by the observed differences in Grem1 expression in different species that correlates with the evolutionary plasticity of tetrapod digit patterning. Hence, a better understanding of spatio-temporal regulation of the Grem1 expression dynamics and underlying cis-regulatory logic is of interest from both adevelopmental and an evolutionary perspective. Recently, multiple candidate CRMs have been identified that might be functionally relevant for Grem1 expression during mouse limb bud development. For my PhD project, I genetically analyzed which of these CRMs are involved in the regulation of the spatial-temporal Grem1 expression dynamics in limb buds. Therefore, we generated various single and compound CRM mutant alleles using CRISPR/Cas9. Our CRMs allelic series revealed a complex Grem1 cis-regulation among a minimum of six CRMs, where a subset of CRMs regulates Grem1 transcript levels in an additive manner. Surprisingly, phenotypic robustness depends not on threshold transcript levels but the spatial integrity of the Grem1 expression domain. In particular, interactions among five CRMs control the characteristic asymmetrical and posteriorly biased Grem1 expression in mouse limb buds. Our results provide an example of how multiple seemingly redundant limb-specific CRMs provide phenotypical robustness by cooperative/synergistic regulation of the spatial Grem1 expression dynamics. Three CRMs are conserved along the phylogeny of extant vertebrates with paired appendages. Of those, the activities of two CRMs recapitulate the major spatiotemporal aspects of Grem1 expression in mouse limb buds. In order to study their functions in species-specific regulation of Grem1 expression and their functional diversification in tetrapods, I tested the orthologous of both CRMs from representative species using LacZ reporter assays in transgenic mice, in comparison to the endogenous Grem1 expression in limb buds of the species of origin. Surprisingly, the activities of CRM orthologues display high evolutionary plasticity, which correlates better with the Grem1 expression pattern in limb buds of the species of origin than its mouse orthologue. This differential responsiveness to the GRNs in mouse suggests that TF binding site alterations in CRMs could underlie the spatial diversification of Grem1 in limb buds during tetrapod evolution. While the fish fin and tetrapod limb share some homologies of proximal bones, the autopod is a neomorphic feature of tetrapods. The Grem1 requirement for digit patterning and conserved expression in fin buds prompted us to assess the enhancer activity of fish CRM orthologues in transgenic mice. Surprisingly, all tested fish CRMs are active in the mouse autopod primordia providing strong evidence that Grem1 CRMs are active in fin buds and that they predate the fin-to-limb transition. Our results corroborate increasing evidence that CRMs governing autopodial gene expression have been co-opted during the emergence of tetrapod autopod. Furthermore, as part of a collaboration with Dr. S. Jhanwar, I contributed to the study of shared and species-specific epigenomic and genomic variations during mouse and chicken limb bud development. In this analysis, Dr. S. Jhanwar identified putative enhancers that show higher chicken-specific sequence turnover rates in comparison to their mouse orthologues, which defines them as so-called chicken accelerated regions (CARs). Here, I analyzed the CAR activities in comparison to their mouse orthologues by transgenic LacZ reporter assays, which was complemented by analysis of the endogenous gene expression in limb buds of both species. This analysis indicates that diversified activity of CARs and their mouse orthologues could be linked to the differential gene expression patterns in limb buds of both species

    The Role of the Metabolome in the Development of Gestational Diabetes Mellitus in High-Risk Minority Women: A Causal Investigation

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    Gestational Diabetes Mellitus (GDM) is the most common pregnancy complication worldwide. However, GDM prevalence is substantially lower in white Europeans (WEs) compared to other ethnicities, especially South Asians (SAs) who experience the highest risk. Globally, healthy diet promotion is the mainstay in GDM prevention, however current guidelines are predominantly based on evidence from WEs. Furthermore, metabolic factors responsible for the disparities in prevalence are unknown but may offer guidance for improved prevention and management. This project aimed to (i) assess the association between diet and GDM across ethnic groups, (ii) determine if distinct metabolic profiles characterise GDM in SAs and WEs, and (iii) evaluate the presence of ethnic-specific causal associations between metabolites and gestational dysglycemia. Aims (ii) and (iii) utilised data from the Born in Bradford cohort (mean gestational age 26.1 weeks). First, through a systematic review of observational and randomised studies, pre-pregnancy diet was found to associate with GDM in WEs, but not in Asians. Secondly, the multivariate analyses of metabolites identified 7 metabolites that were characteristic of GDM in both ethnicities, with an additional 6 characteristic in WEs only. Finally, through Mendelian Randomisation (MR) analyses, 14 metabolites associated with pregnancy dysglycemia in WEs and 11 in SAs. No metabolites were identified in both ethnicities. Cholesterols and fatty acids were the most commonly identified classes identified in WEs and SAs, respectively. This project demonstrated (i) inconsistencies in the association between diet and GDM across ethnicities (ii) distinct metabolic profiles that associate with GDM in WEs and SAs and offers and supports the need for ethnic-specific manage GDM management strategies. In high-risk SAs, fatty acids may be the most important predictors of GDM. Future work should evaluate the role of pre-pregnancy fatty acid intake in GDM development in SAs to aid in the development of culturally tailored dietary interventions

    Adaptation to the family stress model of economic pressure using an actor–partner interdependence mediation model

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    The family stress model of romantic relationships (FSM; Conger et al., 1999) is a well-established tool for examining individual and relationship processes linking economic pressure and marital well-being. Despite the large body of literature utilizing the FSM, gaps remain in our knowledge of differences in the influence of financial stress both within and across couples. Utilizing a sample of 416 different-sex, mostly White, married couples with emerging adolescent children, the current, longitudinal, study adapted the FSM in several ways. Using an actor–partner interdependence mediation model, this study examined direct and indirect spillover and crossover effects between wives’ and husbands’ economic pressure at Wave 1 (when children were in 6th grade) and both their own and their partners’ divorce proneness at Wave 4 (when children were in 9th grade). Additionally, the current study examined two potential moderators: income level (lower, middle, and higher) and work-to-family conflict level (lower and higher). In accordance with the original work conducted by Conger and colleagues, there was no evidence in the current of either spillover or crossover direct effects. Furthermore, support was found for the wives’ hypothesized spillover pathway. Wives’ W1 economic pressure was significantly associated with wives’ depressive symptoms at W2, which were associated with wives’ hostile conflict behaviors at W3 and, finally, with wives’ divorce proneness at W4. Among husbands, there were significant associations between husbands’ economic pressure at W1, husbands’ depressive symptoms at W2 and husbands’ hostile conflict behaviors at W3. However, husbands’ hostile conflict behaviors were not significantly associated with husbands’ divorce proneness at W4. Both wives’ and husbands’ hostile conflict behaviors at W3 were influenced by their partners’ depressive symptoms at W2. Additionally, income was found to significantly moderate the FSM associations. These findings suggests that economic pressure, and it’s resulting influencing on individual well-being and couples’ interaction, operate differently across both gender and income level

    Ägeda faasi valkude kontsentratsiooni muutused, nende seosed ternespiima ja massi-iibega vastsĂŒndinud mĂ€letsejalistel

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    A Thesis for applying for the degree of Doctor of Philosophy in Veterinary Sciences.VĂ€itekiri filosoofiadoktori kraadi taotlemiseks loomaarstiteaduse erialal.Intensive farming has often led to increased spreading of pathogens in herds. After birth, neonatal ruminants are vulnerable to potential pathogens, as the syndesmochorial type of placentation prevents the transfer of antibodies from mother to foetus. Therefore, the vital immune protection will be obtained by passive immune transfer from colostrum. Colostrum contains various bioactive components, e.g. pro-inflammatory cytokines and acute-phase proteins, the effect of which on offspring is the focus of this research. A major role in protection against pathogens is played by the newborn ruminant's innate immune system, part of which is acute-phase reaction, during which the acute phase proteins are synthesised, mainly in the liver. Acute-phase proteins are used as quantitative sensitive inflammatory markers in medicine. In this thesis, the acute phase reaction during the neonatal period of reindeer calves, lambs and dairy calves was investigated by evaluating the acute phase proteins (serum amyloid A, haptoglobin, albumin, fibrinogen). Additionally, the influence of colostrum acute-phase proteins on the neonatal ruminants' acute phase reaction was evaluated. To identify the possible long-term effect of acute phase reaction in the neonatal period, the average daily weight gain in the 3, 4 and in 9 months was measured. During the neonatal period, there is a fluctuation in acute-phase proteins concentration, which is the lowest on the day of birth. The acute phase reaction on the first living week is influenced by colostrum acute phase proteins and pro-inflammatory cytokines. The acute phase reaction on the second and third week of life has a long-term influence on the animal’s growth. Knowledge of the early immunological development of a newborn ruminant allow providing a better growth environment, which means better welfare and preventing the spread of pathogens in intensive farming systems.MĂ€letsejaliste intensiivse pidamisviisiga kaasnevad tihti stressirohkemad pidamistingimused, mis vĂ”ivad pĂ”hjustada haigustekitajate suuremat levimust karjades. Seega on vastsĂŒndinud mĂ€letsejaliste sĂŒnnijĂ€rgne kohanemine vĂ€liskeskkonnaga vĂ€ljakutseterohke. SĂŒnepiteliokoriaalset tĂŒĂŒpi platsenta ei vĂ”imalda antikehade ĂŒlekannet emaloomalt lootele, seega omandab vastsĂŒndinu oma esmase passiivse immuunsuse ternespiimast. Lisaks antikehadele sisaldab ternespiim muid bioaktiivseid komponente, sh proinflammatoorseid tsĂŒtokiine ja Ă€geda faasi valke, mille toime jĂ€rglasele on kĂ€esoleva töö keskmes. VastsĂŒndinu jaoks elutĂ€htsa kaasasĂŒndinud immuunsĂŒsteemi ĂŒheks osaks on Ă€geda faasi vastus, mille kĂ€igus sĂŒnteesitakse proinflammatoorsete tsĂŒtokiinide toimel Ă€geda faasi valke. Neid valke kasutatakse meditsiinis kvantitatiivsete sensitiivsete biomarkeritena. VĂ€itekirjas kĂ€sitleti pĂ”hjapĂ”dravasikate, lambatallede ja piimalehma vasikate Ă€geda faasi vastust neonataalperioodil. Samuti uuriti ternespiimas sisalduvate Ă€geda faasi valkude vĂ”imalikku mĂ”ju vastsĂŒndinu Ă€geda faasi vastusele. Neonataalperioodi Ă€geda faasi vastuse pikemaajalise mĂ”ju selgitamiseks hinnati mÔÔdetud parameetrite seoseid loomade mass-iibega, hinnatuna kolmandal, neljandal ja ĂŒheksandal elukuul. VastsĂŒndinuperioodil esineb kolmel esimesel elunĂ€dalal Ă€geda faasi valkude seerumi amĂŒloid A, haptoglobiini, albumiini ja fibrinogeeni muutusi. SĂŒndimise pĂ€eval on kontsentratsioonid kĂ”ige madalamad. Looma esimese elunĂ€dala Ă€geda faasi vastust mĂ”jutavad ka ternespiimas sisalduvad Ă€geda faasi valgud ja pĂ”letikueelsed tsĂŒtokiinid. Teise ja kolmanda elunĂ€dala Ă€geda faasi vastusel ehk pĂ”letikuprotsessil on pikaajalisem toime, sest see mĂ”jutab negatiivselt looma massi-iivet. Andmed varajaste immunoloogiliste protsesside kujunemise kohta vĂ”imaldavad tootmisloomadele soodsama arengukeskkonna loomist, kus suurendatakse loomade heaolu ning piiratakse haigustekitajate levikut.The publication of this dissertation is granted by the Estonian University of Life Sciences

    Hunting Wildlife in the Tropics and Subtropics

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    The hunting of wild animals for their meat has been a crucial activity in the evolution of humans. It continues to be an essential source of food and a generator of income for millions of Indigenous and rural communities worldwide. Conservationists rightly fear that excessive hunting of many animal species will cause their demise, as has already happened throughout the Anthropocene. Many species of large mammals and birds have been decimated or annihilated due to overhunting by humans. If such pressures continue, many other species will meet the same fate. Equally, if the use of wildlife resources is to continue by those who depend on it, sustainable practices must be implemented. These communities need to remain or become custodians of the wildlife resources within their lands, for their own well-being as well as for biodiversity in general. This title is also available via Open Access on Cambridge Core
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