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Homeostatic set-points are physical and foundational to organism autonomy
No full textLiving systems pose the problem of how a physical system not only maintains itself in a ‘far from equilibrium’ state, but how it determines what state that should be and how it could take the initiative over setting the state, in an act of autonomy that confounds standard physical description. Here I show that the homeostatic set-point is physical information embodied in the structure of evolved enzymes, acting through a series of code and cypher transformations from gene translation, through single molecule dynamics, reaction kinetics, to control system topology and finally physical control. In ‘kinetic regulation’, network topology is determined by the parameters of reaction kinetics and jointly with them, specifies the set-point. Control is added via allosteric manipulation of enzymes based on evolved, not physically inevitable, relationships with effector molecules. This way, enzyme properties alone can determine the set-point. Thus the allosteric enzyme is to homeostasis what the adaptor molecule is to biological code. All the parameters of biochemical regulation result from the way protein structure determines binding affinity and dissociation rates via the shape of electrical forcefields, especially around active sites and effector pockets. In general, the set-point is a highly evolved phenotype having a complicated, but logically inevitable dependence on genotype. By embodying particularising information (the set-point) and using it to do organisational work (homeostasis), even the simplest living system enacts cybernetic independence, characterised by goal-directed behavior, not found in natural abiotic systems.<br/
Hydroxylation mechanism of lignin-derived aromatic substrates catalyzed by plant P450 cinnamate 4-hydroxylase
No full textCytochrome P450 cinnamate 4-hydroxylase (C4H) is a pivotal enzyme in the phenylpropanoid pathway, playing a critical role in regulating lignin biosynthesis in plants. In contrast to the hydroxylation reactions catalyzed by human P450 enzymes, which have been extensively studied, the mechanistic understanding of plant P450-mediated hydroxylation of aromatic substrates remains limited. In this study, using comprehensive atomistic molecular dynamics (MD) simulations, we elucidated the binding pose of the native substrate trans-cinnamic acid and identified key residues contributing to the substrate specificity of the enzyme, which include Arg213 and a conserved hydrophobic pocket comprising Val118, Phe119, Val301, Ala302, Ile367 and Phe484. Additionally, we investigated the catalytic mechanism using hybrid quantum mechanics/molecular mechanics (QM/MM) calculations, evaluating all plausible C4H-catalysed pathways for aromatic hydroxylation. Our results reveal that among all investigated mechanisms, the most favourable pathway involves direct hydroxylation via electrophilic attack coupled with a proton shuttle. These findings provide valuable insights into the catalytic mechanism of C4H, which would pave the way for modifying lignin biosynthesis to regulate various lignin contents in plants, unlocking its potential applications in sustainable bioremediation and biomanufacturing.<br/
Rapid dissolvable microneedles integrated with felodipine-loaded liposome: fabrication, characterizations, in-vitro and ex-vivo evaluation
No full textFelodipine (FD), a calcium channel blocker used to manage hypertension, suffers from poor solubility and low oral bioavailability, which limits its therapeutic efficacy. This study proposes a novel strategy to address this limitation by formulating FD-loaded liposomes (FD-LP) integrated into dissolving microneedles (DMNs), utilizing the biodegradable polymer hydroxypropyl methylcellulose (HPMC) for enhanced transdermal delivery. In the present research, firstly, FD-loaded liposomes were formulated by the thin-film rotary evaporation method and later optimized using Box-Behnken Design (BBD). The optimized FD-LP formulation achieved nanosized vesicles with stable zeta potential and high entrapment efficiency. Methylthiazol tetrazolium (MTT) assay using FD-loaded liposomes against human epidermal keratinocytes (HaCaT) revealed a decrease in cell viability as the concentration of liposomes increased. Secondly, formulation of FD-LP infused into HPMC-based dissolving microneedles to deliver the felodipine transdermally. The resulting FD-LP-DMNs displayed sharp pyramidal microneedles with suitable mechanical strength, effective skin insertion capability, and rapid dissolution of MNs in rat skin. Ex-vivo studies demonstrated the transdermal flux of FD was significantly (4.79 ± 0.03 µg/cm2/hr) improved by FD-LP-DMNs as compared to FD-DMNs. The enhancement ratio of FD-LP-DMNs was 2.77. In conclusion, the integration of FD-loaded liposomes into DMNs shows great promise as a delivery platform for the transdermal administration of FD. This DMN array may serve as a potential approach to a controllable, self-administrative, and rapid transdermal delivery system.<br/
Harnessing volatile organic compound biomarkers for early cancer detection: molecular to nanotechnology-based approaches
No full textEarly-stage cancer diagnosis is considered a grand challenge, and even though advanced analytical assays have been established through molecular biology techniques, there are still clinical limitations. For example, low concentration of target biomarkers at early stages of cancer, background values from the healthy cells, individual variation, and factors like DNA mutations, remain the limiting factor in early cancer detection. Volatile organic compound (VOC) biomarkers in exhaled breath are produced during cancer cell metabolism, and therefore may present a promising way to diagnose cancer at the early stage since they can be detected both rapidly and non-invasively. However, there are challenges in VOC analysis, especially regarding standardization of sampling, necessity for preconcentration, and cancer-specificity of biomarkers. There are also additional challenges, including the design and development of highly sensitive miniaturized sensors that detect VOC biomarkers at low concentrations with minimum cost efforts. In the present article, we have reviewed the potential impact of VOCs in cancer detection in the context of traditional methods such as liquid biopsies, which are typically employed at advanced stages of cancer progression. Described ultrasensitive technologies such as gas chromatography-mass spectrometry (GC-MS) and electronic noses using a variety of nanomaterials have been considered as technologies for breath-based early cancer detection.<br/
Exploring cyanopolyynes towards the C-rich post-AGB star IRAS 22272+5435
No full textCyanopolyynes are a class of long carbon-chain molecules that are widely distributed in interstellar clouds, but their presence in the circumstellar envelopes (CSEs) of evolved stars appears to be limited to only a few well-studied sources. This study aims to search for the presence of cyanopolyynes in the CSE of the C-rich post-asymptotic giant branch (post-AGB) star IRAS 22272+5435 through observational analysis and radiative transfer modelling. Observations were conducted using the Tianma 65 m radio telescope (TMRT) at 15 GHz and the Purple Mountain Observatory (PMO) 13.7 m MM-Wave telescope at 90 GHz. The HCN and HCN transitions were clearly detected in the PMO 13.7 m data, while no significant signals of other cyanopolyynes were detected with TMRT. Based on the observed HCN line, we constructed a spherically symmetric non-thermodynamic equilibrium radiative transfer model, extrapolating the abundance distribution structure from the well-studied C-rich AGB star IRC+10216 to IRAS 22272+5435. The model successfully reproduces the observed HCN and HCN profiles and predicts the line intensities of HCN and HCN. Although the results suggest that these heavier cyanopolyynes may be present in the CSE, their detections are hindered by the large distance and significant beam dilution effects. This study provides valuable observational constraints and theoretical insights into the formation and evolution of carbon-chain molecules in post-AGB environments
Brief communication: qualitative evaluation of call-for-life mHealth tool among youth living with HIV in Uganda
No full textIntroduction: A few studies have assessed the acceptability of mHealth interventions in youth living with HIV, Call For Life -Interactive Voice Response (C4L-IVR) system developed to support patients with HIV and TB in Uganda, specifically to improve treatment adherence and retention in care. This qualitative study examined the acceptability and usage of C4L-IVR, barriers and enablers of adherence and retention in care among youth living with HIV in rural Uganda. Methods: Nested within a randomised intervention trial (NCT04718974), this qualitative study examined youth 16-24 years old, through focus group discussions and in depth interviews at study end. Induction and deduction analysis was done with support of Nvivo software guided by the information motivation behavioral theory.ResultsBetween 9th December 2021 and 28th Apr 2022, 68 participants were recruited, with 38 (56%) females. We conducted 14 interviews 7 focused group discussions (FGD) (02 female only FGD; 5 mixed); and 7 in-depth interviews (IDI) (4 males and 3 females IDI. Seven main themes were identified: information received from the system, motivation from system calls, behavioural skills, barriers to adherence and retention, acceptability of the tool, experiences, and suggestions for improvement. All youth accepted the tool, scoring it highly comfortable on a 5 Likert scale, where 5 was "very comfortable" and 1 "not at all comfortable'. Conclusion: The high acceptability and usage of C4L system along with impact on behavioral skills, this system had more enablers than barriers to ART adherence and retention in care
Exploring the influence of culture on the physical activity routines of elderly individuals with chronic diseases: a scoping review
No full textBackgroundThe global demographic shift towards a population with a more significant proportion of elderly individuals has been associated with notable advancements in medical technology, leading to an increased incidence of chronic illnesses. The importance of healthcare and regular physical activity in preventing illnesses among older adults was emphasised. Consistent participation in exercise has been shown to provide benefits such as decreased vulnerability, lower mortality risk, and improved cognitive abilities. Even with the advantages, there were challenges linked to maintaining a regular exercise routine. The primary objective of this study was to address the current gap in research about the impact of culture on exercise behaviours in the population of older individuals who suffer from chronic diseases. The concept of culture, as published by UNESCO, was used to carry out a comprehensive investigation.MethodsThe main objective of this study is to investigate the influence of cultural variables on the level of participation in physical exercise among elderly adults with chronic illnesses. The research used the framework proposed by Arksey and O’Malley and will conform to the PRISMA-ScR guidelines for documenting systematic reviews. The study used a rigorous process to identify relevant scientific publications published in either English or Arabic during the last twenty years. The accomplishment was achieved by extensively searching many databases, such as OVID Medline, Embase, CINAHL, and Scopus. The investigation includes the period up to June 2023, supported by a meticulous assessment of reference lists to ensure a complete study of the literature.ResultsThe scoping study identified different cultural factors that have a substantial impact on the physical activity habits of older persons with chronic illnesses. Perspectives towards physical activity are influenced by cultural values and beliefs, including ideas of ageing and health. Traditional techniques, such as Tai Chi, are favoured by elder Chinese Americans due to their cultural alignment and ability to increase involvement. Community-based initiatives that include physical activity into everyday schedules, bolstered by local customs and social connections, substantially enhance engagement and compliance. Familial and social networks played a vital role as important motivators, offering both encouragement and practical assistance. In addition, making environmental changes, such as establishing inclusive and culturally suitable communal areas for physical exercise, plays a crucial part in encouraging physical activity. The results underscore the necessity of implementing culturally sensitive, community-oriented, and environmentally supportive approaches to promote physical activity among older persons who have chronic illnesses.ConclusionThis scoping study emphasises the significant influence of cultural influences on the physical activity habits of older persons with chronic illnesses. Efficient interventions should possess cultural sensitivity, be rooted in the community, and receive support from familial and social networks. Customised programmes that integrate local traditions, include community people, and adapt the surroundings to promote physical activity are crucial. Further investigation is warranted to delve into these cultural aspects to devise more efficient and comprehensive health promotion tactics.<br/
Dataset for "Study of thickness distribution on a robotic rotational moulding system by experiment and simulation"
No full textFor 50 years, robotic systems have automated injection moulding. While rotational moulding is less advanced, recent innovations like ROBOMOULD® have improved its process control. This technology uses a 6-axis robot arm to manipulate the mould, enabling precise control over thickness distribution. This dataset is the measurement results from a full factorial study to study the three control parameters (rocking angle, rotations per rock, and robot feed rate or speed) of this robotic rotational moulding system. The moulded parts were produced using an industrial sized fuel tank mould on the robotic moulding system. This study compares experimental and simulated thickness distributions in robotic rotational moulding. A MATLAB-based finite element model predicts thickness distribution based on powder contact time. Results show that robot feeding rate and the interaction between rocking angle and rotations per movement significantly influence thickness distribution. The simplified simulation model accurately predicts trends at higher feeding rates. These measurement results can be used to inform future experiments, calibrate simulation models, or validate existing simulations. The most up-to-date version of this dataset can be found in Queen's University Belfast Open Research Repository (ORR) at https://doi.org/10.17034/30230857.v1 This is the updated version of the dataset, which is available via CC BY 4.0. It relates to the connected research article. An earlier less complete version of the dataset can be found at DOI: 10.17034/2942d476-c73b-4238-8b9b-7800ccbba97
