70015 research outputs found
Sort by
Investigating the Functional Impact of Six Clinically Relevant Variants in Eukaryotic Translation Initiation Factor 3 subunit i (eIF3i) on Global Translation, Growth Rate, and Protein Interaction: A Molecular and Cellular Analysis
No full textmRNA translation is a critical control point in gene expression and biological processes. mRNA translation allows cells and organisms to alter the expression of different genes, at the protein level, according to their needs. The process of mRNA translation is thus highly regulated and complex, involving multiple complex protein interactions and rearrangements. Translation initiation, one of four key stages of translation, is the main focus of this research project. In eukaryotes mRNA translation initiation involves the recruitment of initiation factors, charged tRNA, the 40S ribosomal subunit and the 60S ribosomal subunit, to an activated looped mRNA transcript to allow the formation of the 80S ribosome complex on the mRNA, posed and ready for the next stage of translation, elongation. One of many essential translation initiation factors involved in the translation initiation process in mammalian cells is eukaryotic translation initiation factor 3 subunit i (eIF3i), a component of the 13-subunit eIF3 complex. eIF3i, encoded by the EIF3I gene, is highly conserved and ubiquitously expressed across mammalian tissues. Notably, eIF3i is considered a proto-oncogene, as research has shown it to be overexpressed in certain cancers, where it promotes tumorigenesis and cell proliferation. Overexpression of eIF3i has been linked to colon, breast, head, and neck cancers. Unpublished data from collaborators in Italy have identified six clinically relevant point mutations in eIF3i, which are associated with neurodevelopmental impairments, behavioural abnormalities, and skeletal defects. This project investigated these six point mutations, each resulting in a single amino acid change, by transfecting C-terminal V5-tagged eIF3i plasmids (either wildtype or one of the mutated forms) into HEK293 cells to assess the functional impact of these de novo mutations. The study evaluated several characteristics, comparing the effects of mutant eIF3i expression with wildtype eIF3i overexpression. Protein-protein interactions of eIF3i were examined using immunoprecipitation assays, while global translation activity was assessed through nano-luciferase assays. Additionally, the effects of mutant eIF3i on culture viability, cell growth, and cell diameter were studied using a Vi-Cell instrument and an real-time cell analysis (RTCA) dual purpose (DP) instrument. Key findings from the assays showed that cells expressing mutated eIF3i exhibited faster growth and achieved a higher maximal cell index compared to cells overexpressing wild type eIF3i. Two specific mutants designated Mutant 5 and Mutant 6, produced cell populations with the highest growth rates and cell indices. These results suggest that the mutations confer a growth advantage to the cells. However, despite the increased growth rates, the global translation activity in cells expressing mutant eIF3i was found to be reduced in pools expressing eIF3i transiently but not stably. Immunoprecipitation assays revealed that despite the presence of the mutations, eIF3i was still able to interact with other components of the eIF3 complex (e.g., eIF4G, eIF3c, eIF3j, eIF3a, and eIF3b). Importantly, the mutations did not appear to affect cell viability or culture diameter. In conclusion, this research underscores the need for further investigation into how eIF3i mutations contribute to disease phenotypes, potentially involving roles for eIF3i outside the eIF3 complex. Moreover, further studies are recommended to understand the mechanisms by which mutated eIF3i enhances cell growth while decreasing global translation activity under certain conditions, and how these findings may relate to the neurodevelopmental disorders observed in patients with mutant eIF3i
The future of international labour standards beyond the ILO framework: between trade and human rights
No full textDespite the continued pivotal role of International Labour Organization (ILO) on a global scale and the momentum generated by the post-1998 ILO Declaration, the slowdown in its legislative activity and the criticism directed towards its supervisory bodies, especially in the aftermath of 2012 crisis, have prompted a reassessment of the purpose and approach to international labour standards. Two predominant pathways have emerged for these standards beyond Geneva: firstly, over the past three decades, Free Trade Agreements have incorporated social clauses, ensuring a balanced trade-labour nexus and thereby safeguarding labour standards. Secondly, these standards have become fundamental to the recent development and strengthening of workers’ rights within the Inter-American System of Human Rights. This tailored application of international labour standards, eschewing a one-size-fits-all model, holds the potential to enhance international labour standards beyond the ILO framework
Weak compliance with Nigeria’s wildlife trade ban imposed to curb mpox spillovers
Get PDFZoonotic diseases pose global public health threats, prompting various interventions to limit their emergence and spread. One increasingly common response by governments has been to ban wildlife hunting, trade and consumption. However, there is limited evidence of the effectiveness of wildlife trade bans. Here we assess compliance with Nigeria’s wildlife trade ban—enacted to curb the spread of mpox (formerly monkeypox)—by analysing approximately 4.5 years of wild meat sales data from 19 vendors in southeast Nigeria (988 vendor-months) alongside interviews with vendors and law enforcement officials. After matching the sales data by time of year, we found no significant differences before and after the ban in the number of vendors selling wild meat per week, the weekly mass of wild meat sold, or the weekly price per kilogram of wild meat; however, the total weekly sales price was higher post-ban. These findings, supported by interview insights, indicate widespread non-compliance by vendors, questioning the ban’s effectiveness. We propose that successful regulations require clear enforcement mechanisms, active public engagement and economic incentives to improve compliance. This study provides valuable insights for designing effective interventions to mitigate zoonotic spillovers
Voluntary activity in small rural primary schools: boundaries, networks and trajectories
No full textVoluntary activity - the unpaid and uncoerced giving of time, talent, money, and resources - in primary schools is increasing. However, this increase is not equal, with schools in wealthier areas attracting double the amount of volunteer time and money than those in more deprived areas. Voluntary activity is becoming a necessity rather than a choice, with primary schools increasingly reliant on volunteers and fundraised income. In this context, small schools are experiencing the largest increases in voluntary activity across compulsory education. These are schools with fewer than 100 pupils, often designated as 'rural' by the Department for Education. Whilst frequently conceptualised and promoted as part of a rural idyll in policy and school marketing, England has a highly differentiated countryside, with small schools educating children from a diverse range of backgrounds with a variety of needs. Whilst these schools experience challenges related to their small size, under-prioritisation and underfunding from government, they are often inclusive and caring environments, providing a valuable educational experience difficult to find in larger urban primary schools. Voluntary activity has had and continues to play a vital role in ensuring education can be provided in these contexts. However, it is not well-recognised or researched. It is critical to better understand how voluntary activity happens in different educational contexts and the impact it has on education delivery as well as for staff, students and the volunteers themselves. My research addresses this gap by exploring voluntary activity for two small rural primaries of differing levels of deprivation in Southeast England: Applegood (less deprived) and Oakington (more deprived). This research was conducted through ethnography (2021-2024), with a range of different methods employed during my extended immersion in these schools as a volunteer, researching voluntary activity first-hand. My findings reveal the significance of boundaries and invisible labour, socio-spatial networks and stigma, and trajectories of voluntary activity. My positionality and the methodology adopted (including children's voices) in this research contributes to a holistic and thorough approach to understanding voluntary activity in these environments. This research also contributes to conceptual and theoretical development by working with the total social organisation of labour framework and bringing previously separate fields of literature on educational purpose, parental involvement, gender, capital, stigma, the sociology of work, boundaries, voluntary activity and rurality, into dialogue with each other in the small rural primary context. It also contributes to substantive and policy debates around education and voluntary activity in the current climate
Political Communication and Conspiracy Theory Sharing on Twitter
No full textSocial media has become an influential channel for political communication, offering broad reach while enabling the proliferation of misinformation and conspiracy theories. These unchecked conspiracy narratives may allow manipulation by malign actors, posing dangers to democratic processes. Despite their intuitive appeal, little research has examined the strategic usage and timing of conspiracy theories in politicians’ social media communication compared to the spread of misinformation and fake news.
This study provides an empirical analysis of how members of the U.S. Congress spread conspiracy theories on Twitter. Leveraging the Twitter Historical API, we collected a corpus of tweets from members of the US Congress between January 2012 and December 2022. We developed a classifier to identify conspiracy theory content within this political discourse. We also analyzed the linguistic characteristics, topics and distribution of conspiracy tweets. To assess classifier performance, we created ground truth data through human annotation in which experts labeled a sample of 2500 politicians’ tweets.
Our findings shed light on several aspects, including the influence of prevailing political power dynamics on the propagation of conspiracy theories and higher user engagement. Moreover, we identified specific psycho-linguistic attributes within the tweets, characterized by the use of words related to power and causation, and outgroup language. Our results provide valuable insights into the motivations compelling influential figures to engage in the dissemination of conspiracy narratives in political discourse
Electrotactile Haptic Feedback for use with Remote Surgery Robots
Get PDFThis thesis documents the research, design, implementation and experimental testing of a prototype electrotactile haptic feedback for remote surgery applications, using a 3D-printed electrode array. A literature review was conducted to investigate the current knowledge surrounding the anatomy of the fingertip, electrical characteristics of the skin, somatosensory perception and current electrical stimulation and haptic feedback techniques. Following this, the design methodology was then presented to show the steps taken to achieve the final electrotactile haptic feedback device along with explanations of decisions made. Using the Voltera V-One PCB 3D printer, an electrode array was printed and designed to fit the average index fingertip. This process of printing required a high level of configuration to achieve the levels of accuracy required. This electrode array was connected to an electrical stimulation device capable of electronically controlling the polarity of each electrode. Finally, this device was connected to a VR environment. Following a Current Perception Threshold (CPT) test and a training period, participants were asked to determine the shape presented to them using only their tactile perception within a VR environment. In this single-blind experiment, the presented shape was obscured from the user's view while their fingertip was stimulated using electrotactile haptic feedback. Each of the five participants in this experiment were asked to determine five times what the randomized shape was. These participants correctly identified the shape in 56% of cases overall. When broken down by shape, the percentages were 100%, 40% and 50% for the triangle, square and circle respectively. The triangle is thought to have been identified more consistently due to its unique geometry. The square and circle were identified correctly less consistently; however, they were often mistaken for each other which can be seen in that 77.5% of non-triangle shapes were correctly identified as non-triangle shapes. There appeared to be some correlation between amplitude and the number of shapes correctly identified. Future works should investigate using a larger sample size to improve the reliability of the results across a broader demographic. In these works, it is suggested that a more intricate processing algorithm could be used to investigate creating spatial tactile cues on the fingertip as opposed to the temporal effects presented in this research. Research could also be directed at creating different textures using electrical stimulation rather than edge detection
Molecular nanoarchitectonic sensing layer for analysis of volatile fatty acids in bioreactor headspaces using a nanomechanical sensor
Get PDFAnaerobic digestors (ADs) have the potential to become a major green energy source in a future sustainable society. To achieve this, effective operational parameters of the reactors must be established and maintained preferably by automation. In situ monitoring and control of AD systems is currently a challenging matter based on inconsistent feedstuff composition and the complexity of the biological processes involved, so that reactor shutdowns associated with costly downtime are a common problem. Here, a sensing device is developed for the monitoring of volatile fatty acids (VFAs), key intermediates during bioreactor operation, in the headspaces of anaerobic reactors. The device is compact, contains a sensing element based on a self-assembled molecular layer in conjunction with a nanomechanical sensor, and can be used to monitor VFA contents in bioreactors by estimating their relative contents in the reactor headspace in real time. This device allows the close monitoring of VFA concentrations in admixture toward cost-effective operation of bioreactors by reducing or eliminating reactor downtime. It represents a simple solution to the problem of real-time reactor monitoring, making anaerobic digesters a realistic alternative energy source
Iron(II)–Schiff Base Complexes as Photocatalysts for Controlled Radical Photopolymerization under Light Emitting Diode Irradiation
No full textPhotocatalysts, particularly metal-based complexes, have gained significant attention in photoredox catalysis, enabling controlled radical photopolymerization (CRP2) under mild irradiation conditions, such as sunlight or LED bulbs. In this study, three Fe(II) complexes−FeIISalen, FeIISaloex, and FeIISalophen−bearing non-symmetrical Schiff base ligands were synthesized and designed for potential application in CRP2. The complexes were characterized using FTIR, UV-Vis, and fluorescence spectroscopy, MALDI-TOF mass spectrometry, and elemental analysis. Additionally, density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations were conducted to extract key structural, electronic, and excited-state properties. The catalytic performance of these Fe(II) complexes in the CRP2 of methyl acrylate (MA) was evaluated under different conditions, using ethyl α-bromophenylacetate (EBPA) as the initiator and triethylamine (TEA) as the electron donor. The photopolymerizations proceeded efficiently, yielding polymers with controlled molecular weights and narrow molecular weight distributions (MWD). Among the tested photocatalysts, FeIISaloex exhibited the best performance, achieving high conversion and low polydispersity under LED irradiation. Furthermore, a mechanism was proposed based on spectroscopic analyses and literature data
Predictors of 30-day readmission among those treated with alcohol withdrawal in acute hospitals in England
Get PDFAims: To examine predictors of 30-day readmissions to acute hospitals in England for patients treated for alcohol withdrawal (AW).
Methods: Retrospective cross-sectional analysis of routine hospital administrative data (i.e. Hospital Episode Statistics—Admitted Patient Care records) for adults admitted to non-specialist hospitals in England 2017–18.
Results: AW admissions were associated with digestive, circulatory, respiratory, and endocrine disorders and were of short duration (median 3 days). Of the 19 588 completed AW admissions examined in 2017–18, 3957 (20.2%) resulted in readmission within 30 days. The strongest predictors of 30-day readmission were being no fixed abode (Adjusted Odds Ratio (AOR) 1.81, 95%CI 1.44–2.26), prior discharge against medical advice (AOR 1.57, 95%CI 1.40–1.77), and greater Charlson comorbidity index total score (AOR 1.02, 95%CI 1.02–1.03).
Discussion: AW 30-day admissions are common and associated to complex case presentations that require high levels of community support on discharge. Hospital-based alcohol teams should prioritize strategies, which maximize medically managed AW, effective transitions to specialist community care including outreach teams and strong collaborations with physical and mental health outpatient services. Together with specialist initiatives within community mental health teams, assertive outreach, and homeless services 30-day readmissions may be minimized
The weaker vessel. Survival tactics of women entrepreneurs in Ghana’s informal economy
Get PDFThis article examines how informal women entrepreneurs in Ghana navigate structural constraints to build thriving businesses. Drawing on De Certeau’s concept of ‘Tactics as an Art of the Weak’, we explore how these entrepreneurs exercise agency in the institutionally and resource-constrained environment of Ghana. Using a qualitative approach to collect data, we identify two forms of tactics: tactical resistances, where women subtly or overtly challenge restrictive policies by avoiding, defying, or bypassing regulations, and tactical alternatives/workarounds, where they creatively work around constraints by leveraging informal support systems. Our findings contribute valuable insights to the discourse on how entrepreneurial agency is enacted by a group of entrepreneurs for whom the success of their businesses is their only hope of survival. We offer research and policy implications that are relevant for empowering marginalised entrepreneurs and promoting sustainable economic empowerment for women in similar contexts
Access Repository Dashboard
Do you manage Kent Academic Repository? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!