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1.
RSC Adv ; 11(52): 33124-33135, 2021 Oct 04.
Article in English | MEDLINE | ID: mdl-35493559

ABSTRACT

Cellular metabolism and behaviour is closely linked to cytoskeletal tension and scaffold mechanics. In the developing nervous system functional connectivity is controlled by the interplay between chemical and mechanical cues that initiate programs of cell behaviour. Replication of functional connectivity in neuronal populations in vitro has proven a technical challenge due to the absence of many systems of biomechanical regulation that control directional outgrowth in vivo. Here, a 3D culture system is explored by dilution of a type I collagen hydrogel to produce variation in gel stiffness. Hydrogel scaffold remodelling was found to be linked to gel collagen concentration, with a greater degree of gel contraction occurring at lower concentrations. Gel mechanics were found to evolve over the culture period according to collagen concentration. Less concentrated gels reduced in stiffness, whilst a biphasic pattern of increasing and then decreasing stiffness was observed at higher concentrations. Analysis of these cultures by PCR revealed a program of shifting integrin expression and highly variable activity in key morphogenic signal pathways, such as mitogen-associated protein kinase, indicating genetic impact of biomaterial interactions via mechano-regulation. Gel contraction at lower concentrations was also found to be accompanied by an increase in average collagen fibre diameter. Minor changes in biomaterial mechanics result in significant changes in programmed cell behaviour, resulting in adoption of markedly different cell morphologies and ability to remodel the scaffold. Advanced understanding of cell-biomaterial interactions, over short and long-term culture, is of critical importance in the development of novel tissue engineering strategies for the fabrication of biomimetic 3D neuro-tissue constructs. Simple methods of tailoring the initial mechanical environment presented to SH-SY5Y populations in 3D can lead to significantly different programs of network development over time.

2.
Early Hum Dev ; 145: 105038, 2020 06.
Article in English | MEDLINE | ID: mdl-32311647

ABSTRACT

Aim To determine parents' experiences on a neonatal unit in a low-income country, how they and staff perceive the role of parents and if parents' role as primary carers could be extended. BACKGROUND: A busy, rural district hospital in Rwanda. Rwandan neonatal mortality is falling, but achieving Sustainable Development Goal target is hampered by trained staff shortage. METHODS: Qualitative thematic content analysis of semi-structured interviews with 12 parents and 16 staff. RESULTS: Parental concerns were around their baby's survival, stress and discharge. They were satisfied with their baby's care but feared their baby may die. Mothers described stress from remaining in hospital throughout baby's stay, providing all non-technical care including tube or breast feeds day and night, followed by kangaroo mother care until discharge. They expressed loneliness from lack of visitors, difficulty finding food and somewhere to sleep, financial worries, concern about family at home, and were desperate to be discharged. Staff focused on shortage of nurses limiting technical care, ability to educate parents and provide follow-up. Neither groups thought parents' role could be extended. CONCLUSION: Staff, including senior management, were mainly focused on increasing nursing numbers. Parents' concerns were psychosocial and about coping emotionally with their baby's care and practical concerns about inpatient facilities, particularly lack of food and accommodation and absence from home. Staff preoccupation with nurse numbers made them concentrate on medical care, but parental issues identified are more likely to be provided by experienced mothers, allied health professionals, mothers' groups or community health workers.


Subject(s)
Attitude , Caregiver Burden/epidemiology , Health Personnel/psychology , Intensive Care, Neonatal/psychology , Parents/psychology , Adult , Developing Countries , Female , Humans , Infant, Newborn , Intensive Care, Neonatal/methods , Male , Rwanda
3.
Methods Cell Biol ; 135: 451-81, 2016.
Article in English | MEDLINE | ID: mdl-27443940

ABSTRACT

The Zebrafish Model Organism Database (ZFIN; zfin.org) serves as the central repository for genetic and genomic data produced using zebrafish (Danio rerio). Data in ZFIN are either manually curated from peer-reviewed publications or submitted directly to ZFIN from various data repositories. Data types currently supported include mutants, transgenic lines, DNA constructs, gene expression, phenotypes, antibodies, morpholinos, TALENs, CRISPRs, disease models, movies, and images. The rapidly changing methods of genomic science have increased the production of data that cannot readily be represented in standard journal publications. These large data sets require web-based presentation. As the central repository for zebrafish research data, it has become increasingly important for ZFIN to provide the zebrafish research community with support for their data sets and guidance on what is required to submit these data to ZFIN. Regardless of their volume, all data that are submitted for inclusion in ZFIN must include a minimum set of information that describes the data. The aim of this chapter is to identify data types that fit into the current ZFIN database and explain how to provide those data in the optimal format for integration. We identify the required and optional data elements, define jargon, and present tools and templates that can help with the acquisition and organization of data as they are being prepared for submission to ZFIN. This information will also appear in the ZFIN wiki, where it will be updated as our services evolve over time.


Subject(s)
Databases, Genetic , Genomics/methods , Zebrafish/genetics , Animals , Animals, Genetically Modified , Genome/genetics , Morpholinos/genetics , Mutation
4.
Cell Death Dis ; 7: e2184, 2016 Apr 07.
Article in English | MEDLINE | ID: mdl-27054339

ABSTRACT

The integrity of the genome is maintained by a host of surveillance and repair mechanisms that are pivotal for cellular function. The tumour suppressor protein p53 is a major component of the DNA damage response pathway and plays a vital role in the maintenance of cell-cycle checkpoints. Here we show that a microRNA, miR-486, and its host gene ankyrin-1 (ANK1) are induced by p53 following DNA damage. Strikingly, the cytoskeleton adaptor protein ankyrin-1 was induced over 80-fold following DNA damage. ANK1 is upregulated in response to a variety of DNA damage agents in a range of cell types. We demonstrate that miR-486-5p is involved in controlling G1/S transition following DNA damage, whereas the induction of the ankyrin-1 protein alters the structure of the actin cytoskeleton and sustains limited cell migration during DNA damage. Importantly, we found that higher ANK1 expression correlates with decreased survival in cancer patients. Thus, these observations highlight ANK1 as an important effector downstream of the p53 pathway.


Subject(s)
Ankyrins/genetics , Ankyrins/metabolism , DNA Damage , Tumor Suppressor Protein p53/metabolism , Up-Regulation/genetics , Actin Cytoskeleton/metabolism , Ankyrins/antagonists & inhibitors , Antibiotics, Antineoplastic/pharmacology , Blotting, Western , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Cell Line , Cell Movement/drug effects , DNA Damage/drug effects , DNA Repair , Doxorubicin/pharmacology , Female , Humans , MicroRNAs/antagonists & inhibitors , MicroRNAs/genetics , MicroRNAs/metabolism , Microscopy, Fluorescence , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA Interference , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Tumor Suppressor Protein p53/antagonists & inhibitors , Tumor Suppressor Protein p53/genetics
5.
Aging Ment Health ; 10(4): 394-403, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16798632

ABSTRACT

Approximately 40% of older people in residential care have significant symptoms of depression. A training and care-planning approach to reducing depression was implemented for 114 depressed residents living in 14 residential care homes in North Yorkshire, UK. Care staff were offered brief mental health training by community mental health teams for older people. They were then assigned to work individually with residents in implementing the care-planning intervention, which was aimed at alleviating depression and any health, social or emotional factors that might contribute to the resident's depression. Clinically significant improvements in depression scores were associated with implementation of the care-planning intervention as evidenced by changes in scores on the Geriatric Mental State Schedule-Depression Scale. There was evidence of an interaction between the power of the intervention and degree of dementia. These improvements were not accounted for by any changes in psychotropic medication. The training was highly valued by care staff and heads of homes, and they considered that the care-planning intervention represented an improvement in quality of care for all residents, irrespective of levels of dementia. Staff also reported improvements in morale and increased confidence in the caring role as a result of their participation. The limitations of this study are discussed. On the basis of a growing body of evidence, it is argued that there is an urgent need for a suitably powered randomised controlled trial and economic evaluation, to test the cost-effectiveness of personalised care planning interventions aimed at reducing depression in older people in residential care.


Subject(s)
Depressive Disorder/prevention & control , Health Services for the Aged/standards , Inservice Training/methods , Patient-Centered Care/methods , Residential Facilities/methods , Adult , Aged , Aging/psychology , Depressive Disorder/psychology , Female , Health Services for the Aged/statistics & numerical data , Humans , Job Satisfaction , Male , Mental Health Services/standards , Mental Health Services/statistics & numerical data , Morale , Patient-Centered Care/statistics & numerical data , Pilot Projects , Psychiatric Status Rating Scales/statistics & numerical data , Residential Facilities/standards , Residential Facilities/statistics & numerical data , United Kingdom
7.
Nutr Health ; 4(1): 29-36, 1985.
Article in English | MEDLINE | ID: mdl-3834354

ABSTRACT

The past few years have witnessed a growing literature on the behavioural, cognitive and performance effects, both beneficial and hazardous, of caffeine ingestion. A brief overview of these studies is provided and methodological difficulties discussed. Disagreement over such factors as the quantity of caffeine required to produce deleterious effects, difficulties obtaining valid measures of caffeine intake from self-reports and differing interpretations of tolerance levels and absorption rates between studies, often prevent the derivation of meaningful results. The need for a rigorous, scientific appraisal of the effects of caffeine on psychological functioning is emphasised. This requires agreement about criteria referred to above, a more valid data base, and in some cases, the adoption of alternative methodology.


Subject(s)
Behavior/drug effects , Caffeine/pharmacology , Cognition/drug effects , Caffeine/administration & dosage , Humans , Research Design , Time Factors
8.
J Comp Neurol ; 162(2): 221-45, 1975 Jul 15.
Article in English | MEDLINE | ID: mdl-1150920

ABSTRACT

A three-dimensional block model of the cochlear nucleus of the cat was constructed from histologic sections. Boundaries of various subdivisions, based on cytoarchitectonic criteria, were included in the model. Usage of the block model in correlating physiological and anatomical data is illustrated by localizing characteristic waveforms of gross evoked responses and characteristic frequencies of single units.


Subject(s)
Cochlear Nerve/physiology , Animals , Cats , Cochlear Nerve/anatomy & histology , Electric Stimulation , Evoked Potentials , Models, Neurological
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