Gene Therapy for Parkinson's Disease

Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field

Effect of isomorphic forces on safety practices in service organizations – are there dangers to homogeneity?

A wide range of different safety practices exist. However, they have been developed for production-oriented high-hazard environments. We know relatively little about safety practices in low-hazard service sector environments where most people in the U.K work and which differ from production-oriented industries in their organization, working practices and hazards. We conducted 143 semi-structured interviews in 10 stores of four leading U.K retailers and an office and two warehouses of a global logistics company. These revealed 32 categories of safety practices in these service organizations which we aligned to those indicated in the OHSAS 18001 framework to allow comparison across industries. There were few practices that were not common to all service environments. Moreover, these closely resembled safety practices conducted in production-oriented high-hazard environments. We explain this homogeneity by institutional isomorphism, which encourages conformity through coercive, normative and mimetic pressures arising respectively from legal and regulatory requirements, professional standards and training, and lack of resources and staff turnover. We draw attention to the contingent relationship between hazards and appropriate safety practices and conclude that these pressures encourage organizations to borrow practices inappropriately and to accumulate layers of practices to ensure safe working needlessly increasing organizational costs. Opportunities for further research are discussed

City of clones: Facsimiles and governance in Sao Paulo, Brazil

São Paulo is a megacity defined by formal and informal patterns of urbanization. Informally urbanized spaces are not absent of state intent, despite appearances. Grassroots-led social and spatial practices for survival, agency and self-governance contribute to the reproduction of urban political order in surprisingly unoriginal and routinely recognizable ways. This article argues that these unexceptional informal practices can be understood as ‘facsimiles’ of their formal institutional originals. Using the example of cloned cars the article shows that the facsimile and the original are the same in form and function. Facsimiles do not exist outside of political authority, but are a byproduct and a component of it. They are indistinguishable in their bureaucratic deployment, recognition and acceptance as part of social and spatial order. This is the author accepted manuscript. The final version is available from Sage via https://doi.org/10.1177/001139211665729

Fourth-Order Butterworth Active Bandpass Filter Design for Single-Sided Magnetic Particle Imaging Scanner

This paper describes the design and simulation of a fourth-order Butterworth active bandpass filter designed for single-sided magnetic particle imaging (MPI) scanner. Bandpass filters (BPF) are used in MPI scanner set-up to attenuate the harmonic distortions generated by the power amplifier before passing the purely sinusoidal signal to the excitation (Drive) coils. The BPF is designed based on the excitation frequency of 22.8 kHz, having Butterworth response, and realized using Sallen-Key topology by cascading one second-order highpass filter and one second-order lowpass filter, with values of the passive components calculated using the coefficient matching method. MATLAB and NI Multisim software are used to simulate the filter, and the results are compared. The magnitude response obtained using MATLAB have monotonic amplitude response in the pass and stopband, and maximally flat with small ripples in the passband than the NI Multisim implementation, while NI Multisimimplementation has better roll-off than MATLAB implementation

Formation of the Stomatal Outer Cuticular Ledge Requires a Guard Cell Wall Proline-Rich Protein

Stomata are formed by a pair of guard cells which have thickened, elastic cell walls to withstand the large increases in turgor pressure that have to be generated to open the pore that they surround. We have characterised FOCL1, a guard cell-expressed, secreted protein with homology to hydroxyproline-rich cell wall proteins. FOCL1-GFP localises to the guard cell outer cuticular ledge and plants lacking FOCL1 produce stomata without a cuticular ledge. Instead the majority of stomatal pores are entirely covered-over by a continuous fusion of the cuticle, and consequently plants have decreased levels of transpiration and display drought tolerance. The focl1 guard cells are larger and less able to reduce the aperture of their stomatal pore in response to closure signals suggesting that the flexibility of guard cell walls is impaired. FOCL1 is also expressed in lateral root initials where it aids lateral root emergence. We propose that FOCL1 acts in these highly specialised cells of the stomata and root to impart cell wall strength at high turgor and/or to facilitate interactions between the cell wall and the cuticle

Transcriptomic Analyses of Inner Ear Sensory Epithelia in Zebrafish

Analysis of gene expression has the potential to assist in the understanding of multiple cellular processes including proliferation, cell-fate specification, senesence, and activity in both healthy and disease states. Zebrafish model has been increasingly used to understand the process of hearing and the development of the vertebrate auditory system. Within the zebrafish inner ear, there are three otolith organs, each containing a sensory macula of hair cells. The saccular macula is primarily involved in hearing, the utricular macula is primarily involved in balance and the function of the lagenar macula is not completely understood. The goal of this study is to understand the transcriptional differences in the sensory macula associated with different otolith organs with the intention of understanding the genetic mechanisms responsible for the distinct role each organ plays in sensory perception. The sensory maculae of the saccule, utricle, and lagena were dissected out of adult Et(krt4:GFP) zebrafish expressing green fluorescent protein in hair cells for transcriptional analysis. The total RNAs of the maculae were isolated and analyzed by RNA GeneChip microarray. Several of the differentially expressed genes are known to be involved in deafness, otolith development and balance. Gene expression among these otolith organs was very well conserved with less than 10% of genes showing differential expression. Data from this study will help to elucidate which genes are involved in hearing and balance. Furthermore, the findings of this study will assist in the development of the zebrafish model for human hearing and balance disorders. Anat Rec, 303:527-543, 2020. © 2019 American Association for Anatomy

Standardisation of a mental skills scale in South Africa and the United Kingdom

The contemporary science of sport and exercise psychology requires the standardisation of mental skills questionnaires to facilitate accurate assessment of and intervention for individuals and groups in various health and sport related contexts. The study presents international research findings regarding the standardisation of a Mental Skills Scale with a sample of university students (N=420) from South Africa (n=211) and the United Kingdom (n=209) respectively. Although further international and national standardisation in both English and other languages is recommended, factor and reliability analyses indicated satisfactory validity and reliability of the current English version of the scale

More than sense of place? Exploring the emotional dimension of rural tourism experiences

It is widely suggested that participation in rural tourism is underpinned by a sense of rural place or “rurality”. However, although nature and the countryside have long been recognised as a source of spiritual or emotional fulfilment, few have explored the extent to which tourism, itself often claimed to be a sacred experience, offers an emotional/spiritual dimension in the rural context. This paper addresses that literature gap. Using in-depth interviews with rural tourists in the English Lake District, it explores the extent to which, within respondents’ individual understanding of spirituality, a relationship exists between sense of place and deeper, emotional experiences and, especially, whether participation in rural tourism may induce spiritual or emotional responses. The research revealed that all respondents felt a strong attachment to the Lake District; similarly, and irrespective of their openness to spirituality, engaging in rural tourism activities resulted in highly emotive experiences for all respondents, the description/interpretation of such experiences being determined by individual “beliefs”. However, sense of place was not a prerequisite to emotional or spiritual experiences. Being in and engaging with the landscape � effectively becoming part of it � especially through physical activity is fundamental to emotional responses

What can we learn from the implementation of monetary and macroprudential policies: a systematic literature review

The emergence of macroprudential policies, implemented by central banks as a means of promoting financial stability, has raised many questions regarding the interaction between monetary and macroprudential policies. Given the limited number of studies available, this paper sheds light on this issue by providing a critical and systematic review of the literature. To this end, we divide the theoretical and empirical studies into two broad channels of borrowers - consisting of the cost of funds and the collateral constraint - and financial intermediaries - consisting of risk-taking and payment systems. In spite of the existing ambiguity surrounding coordination issues between monetary and macroprudential policies, it is argued that monetary policy alone is not sufficient to maintain macroeconomic and financial stability. Hence, macroprudential policies are needed to supplement monetary. Additionally, we find that the role of the exchange rate is critical in the implementation of monetary and macroprudential policies in emerging markets, whilst volatile capital flows pose another challenge. In so far as how the arrangement of monetary and macroprudential policies varies across countries, key theoretical and policy implications have been identified

Cell envelope proteins of Staphylococcus epidermidis grown in vivo in a peritoneal chamber implant

Staphylococcus epidermidis was grown in vivo in chambers implanted intraperitoneally in rats. The cell wall and cytoplasmic membrane protein profiles of the in vivo-grown organisms were compared with those of S. epidermidis grown in vitro in nutrient broth (NB), in iron-restricted NB, or in pooled human peritoneal dialysate (HPD). Compared with growth in broth and in common with growth in HPD, growth in vivo in chambers resulted in the repression of many S. epidermidis wall proteins, with proteins of 27, 42, 54, and 70 kDa predominating. Growth in vivo also resulted in the induction of two iron-repressible cytoplasmic membrane proteins of 32 and 36 kDa, which were also present in staphylococci grown in HPD and in iron-restricted NB. Immunoblotting experiments revealed that in sera taken 21 days after inoculation of the intraperitoneal chambers, the predominant antibody response to cell envelope proteins was directed against the 32- and 36-kDa iron-repressible membrane proteins