‘Our voice started off as a whisper and now it is a great big roar’ : The Salford Dementia Associate Panel as a model of involvement in research activities

This paper presents the work of the ‘Salford Dementia Associate Panel’, based at the Salford Institute for Dementia, Salford University (UK). We discuss the roles of the Dementia Associates, in particular around the areas of engagement and research. The panel is made up of people living with dementia, and current and former care partners. It highlights the development of this group over a four-year period and demonstrates over time how the role of a Dementia Associate member has evolved. The panel is involved in research, education and public engagement activities conducted by staff and students within the Institute. The motivations for becoming involved are clearly articulated and demonstrate how the personal backgrounds of individuals have driven the collective involvement and desire to bring about change. The benefits and challenges associated with working as part of a panel are discussed. We conclude by bringing together our experiences as a set of suggestions for others who may wish to create a similar forum to promote the involvement of people living with dementia and former and current care partners

Plasmodium genes responsible for oocyst development and interaction with its Anopheline vector

The transmission of the malaria parasite Plasmodium is governed by a complex developmental cycle. This PhD thesis describes the transcriptional profiling of the rodent malaria parasite Plasmodium berghei developmental migration through its A. gambiae vector. The study was conducted in vivo, using a near complete P. berghei genome microarray platform. Emphasis was placed on the oocyst stage, as little is known about the genes implicated in the ookinete to oocyst transition, and oocyst maturation. The data presented here provide novel transcriptional information about Plasmodium transmission. The analysis revealed a large shift in gene utilisation as the parasite makes its transition from the motile ookinete to the sessile oocyst. Furthermore, this work has shown that different sets of co-regulated genes are important for early and late oocyst development. In addition, this PhD thesis outlines the characterisation of a novel Plasmodium formin-like protein essential for rodent malaria transmission named the male inherited sporulation factor important for transmission (misfit). MISFIT is expressed in the early mosquito stages, where the protein localises to the parasite nucleus. Misfit exhibits an absolute requirement for paternal inheritance, which is in accordance with an observed male-biased expression pattern. pbmisfitΔ ookinetes display significant ultrastructural and gene expression defects and fail to complete zygotic meiosis. However, pbmisfitΔ ookinetes retain functionality and can successfully cross the midgut epithelial barrier. In contrast, mosquito infections with pbmisfitΔ resulted in an arrest immediately upon ookinete-oocyst transformation, where defective oocysts fail to sporulate. An essential role in chromosome segregation during mitosis / meiosis is postulated for MISFIT. In conclusion, the work presented in this thesis has established the ookinete-oocyst transition as a major cell cycle check point during malaria transmission and identified misfit as the first male inherited Plasmodium gene known to affect development post-fertilisation

A Description of an Improved Homodyne Laser Interferometer

First appearing on the commercial market in the mid 1980’s, diode-pumped, continuous-wave (cw) Nd:YAG lasers have more recently been used to obtain visible output, by the incorporation of frequency doubling optics in the laser cavity.The laser diode pumping of a Nd:YAG laser rod is selective and highly efficient, resulting in compact, high power, spatial mode lasers. Frequency-doubling processes are non-linear and lead to doubling TEM00 only of the high energy fundamental temporal mode, resulting in operation of the 532 nm laser in a single spatial and single longitudinal mode. The technology is rapidly advancing, and green lasers with energies of up to 1W could soon be available. The beam properties of the lasers described above are highly desirable in the field of interferometry, where such lasers are now in direct competition with the much larger Argon lasers, which have already been employed in high power interferometric systems. We describe here the performance of a modified Michelson interferometer [1–4], built to incorporate a 90 mW ADLAS 300 diode-pumped Nd:YAG laser. In previous versions of the Michelson interferometer, we have used HeNe lasers with a few milliwatts output, requiring mirror-quality surfaces on our samples. A 90 mW laser power enables us to make displacement measurements on metal surfaces with little or no preparation. The laser could also, of course, be used in other, more elaborate interferometer types, such as the confocal Fabry-Perot, which are better suited to industrial environments

CRISPR/Cas9 and genetic screens in malaria parasites : small genomes, big impact

The ∼30 Mb genomes of the Plasmodium parasites that cause malaria each encode ∼5000 genes, but the functions of the majority remain unknown. This is due to a paucity of functional annotation from sequence homology, which is compounded by low genetic tractability compared with many model organisms. In recent years technical breakthroughs have made forward and reverse genome-scale screens in Plasmodium possible. Furthermore, the adaptation of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-Associated protein 9 (CRISPR/Cas9) technology has dramatically improved gene editing efficiency at the single gene level. Here, we review the arrival of genetic screens in malaria parasites to analyse parasite gene function at a genome-scale and their impact on understanding parasite biology. CRISPR/Cas9 screens, which have revolutionised human and model organism research, have not yet been implemented in malaria parasites due to the need for more complex CRISPR/Cas9 gene targeting vector libraries. We therefore introduce the reader to CRISPR-based screens in the related apicomplexan Toxoplasma gondii and discuss how these approaches could be adapted to develop CRISPR/Cas9 based genome-scale genetic screens in malaria parasites. Moreover, since more than half of Plasmodium genes are required for normal asexual blood-stage reproduction, and cannot be targeted using knockout methods, we discuss how CRISPR/Cas9 could be used to scale up conditional gene knockdown approaches to systematically assign function to essential genes.Instituto de BiotecnologíaFil: Ishizaki, Takahiro. Umeå University. Department of Molecular Biology; SueciaFil: Ishizaki, Takahiro. The Laboratory for Molecular Infection Medicine Sweden (MIMS); SueciaFil: Hernandez, Sophia. Umeå University. Department of Molecular Biology; SueciaFil: Hernandez, Sophia. The Laboratory for Molecular Infection Medicine Sweden (MIMS); SueciaFil: Paoletta, Martina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Paoletta, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paoletta, Martina. Umeå University. Department of Molecular Biology; SueciaFil: Paoletta, Martina. The Laboratory for Molecular Infection Medicine Sweden (MIMS); SueciaFil: Sanderson, Theo. Francis Crick Institute; Reino UnidoFil: Bushell, Ellen S. C. Umeå University. Department of Molecular Biology; SueciaFil: Bushell, Ellen S. C. The Laboratory for Molecular Infection Medicine Sweden (MIMS); Sueci

Cell-autonomous programming of rat adipose tissue insulin signalling proteins by maternal nutrition.

AIMS/HYPOTHESIS: Individuals with a low birthweight have an increased risk of developing type 2 diabetes mellitus in adulthood. This is associated with peripheral insulin resistance. Here, we aimed to determine whether changes in insulin signalling proteins in white adipose tissue (WAT) can be detected prior to the onset of impaired glucose tolerance, determine whether these changes are cell-autonomous and identify the underlying mechanisms involved. METHODS: Fourteen-month-old male rat offspring born to dams fed a standard protein (20%) diet or a low (8%) protein diet throughout gestation and lactation were studied. Fat distribution and adipocyte size were determined. Protein content and mRNA expression of key insulin signalling molecules were analysed in epididymal WAT and in pre-adipocytes that had undergone in vitro differentiation. RESULTS: The offspring of low protein fed dams (LP offspring) had reduced visceral WAT mass, altered fat distribution and a higher percentage of small adipocytes in epididymal WAT. This was associated with reduced levels of IRS1, PI3K p110β, Akt1 and PKCζ proteins and of phospho-Akt Ser473. Corresponding mRNA transcript levels were unchanged. Similarly, in vitro differentiated adipocytes from LP offspring showed reduced protein levels of IRβ, IRS1, PI3K p85α and p110β subunits, and Akt1. Levels of Akt Ser473 and IRS1 Tyr612 phosphorylation were reduced, while IRS1 Ser307 phosphorylation was increased. CONCLUSIONS/INTERPRETATION: Maternal protein restriction during gestation and lactation changes the distribution and morphology of WAT and reduces the levels of key insulin signalling proteins in the male offspring. This phenotype is retained in in vitro differentiated adipocytes, suggesting that programming occurs via cell-autonomous mechanism(s).This work was supported by Diabetes UK (MSM-G; no. 12/0004508), the British Heart Foundation (SEO; no. FS/09/029/27902) and the UK Medical Research Council (SEO; no. MC_UU_12012/4)This is the accepted manuscript. It is currently embargoed pending publication

Using climate information to support crop breeding decisions and adaptation in agriculture

Population growth in the next few decades will increase the need for food production, while the yields of major food crops could be impacted by the changing climate and changing threats from pests and pathogens. Crop breeding, both through conventional techniques, and GM assisted breeding could help meet these challenges, if adequately supported by appropriate information on the future climate. We highlight some of the major challenges for crop breeders and growers in the coming decades, and describe the main characteristics of crop breeding techniques and other adaptation options for agriculture. We review recent uses of climate information to support crop breeding decisions and make recommendations for how this might be improved. We conclude that there is significant potential for breeders to work more closely with climate scientists and crop modellers in order to address the challenges of climate change. It is not yet clear how climate information can best be used. Fruitful areas of investigation include: provision of climate information to identify key target breeding traits and develop improved success criteria (e.g. for heat/drought stress); identification of those conditions under which multiple stress factors (for example, heat stress, mid-season drought stress, flowering drought stress, terminal drought stress) are important in breeding programmes; use of climate information to inform selection of trial sites; identification of the range of environments and locations under which crop trials should be performed (likely to be a wider range of environments than done at present); identification of appropriate duration of trials (likely to be longer than current trials, due to the importance of capturing extreme events); and definition of appropriate methods for incorporating climate information into crop breeding programmes, depending on the specific needs of the breeding programme and the strengths and weaknesses of available approaches. Better knowledge is needed on climate-related thresholds important to crop breeders, for example on the frequency and severity of extreme climate events relevant to the product profile, or to help provide tailored climate analyses (particularly for extreme events). The uncertainties inherent in climate and impact projections provide a particular challenge for translating climate science into actionable outcomes for agriculture. Further work is needed to explore relevant social and economic assumptions such as the level and distribution of real incomes, changing consumption patterns, health impacts, impacts on markets and trade, and the impact of legislation relating to conservation, the environment and climate change

Music making in the community with people living with dementia and care partners – ‘I’m leaving feeling on top of the world’

Evidence exists relating to music-based initiatives and positive health outcomes for people living with dementia who can access them. Yet, knowledge about the impact of ‘music-making’ on the wellbeing of community dwelling people with dementia is limited. Much of the existing evidence about the benefits of music is focused on care home settings where initiatives can be readily applied as part of a weekly schedule of activities. Therefore, this initiative aimed to provide opportunities to participate in music-making, to increase social interaction and ultimately wellbeing in a community environment. Ten music-making session were scheduled for community dwelling people living with dementia and care-partners, once a month between September 2019 and March 2020. Three sessions did not take place due to Covid19. Eighteen participants consented to take part including 7 people living with dementia, 5 care-partners and 6 former care-partners. Baseline semi-structured interviews explored the lived experience of music and expectations of the upcoming music-making cafes. Self-report questionnaires captured ‘in the moment’ experiences of each music-making cafe. Follow-up semi-structured interviews explored the impact of music-making on participants self-reported wellbeing. Interviews were transcribed verbatim and analysed thematically. The findings demonstrate that participating in the music-making café benefitted the self-reported wellbeing of participants in three ways: first, a sense of camaraderie that enabled the facilitation of connections with others; second, creating opportunities to ‘level the playing field’ by always assuming a person’s strengths and abilities; third, group participation in musicmaking meets a need for meaningful musical experiences. We conclude that participating in musicmaking is a powerful medium to promote wellbeing for community dwelling people living with dementia and care-partners

Using the Massachusetts Youth Screening Instrument–Version 2 on a Community Sample of African American and Latino/a Juvenile Offenders to Identify Mental Health and Substance Abuse Treatment Needs

The Massachusetts Youth Screening Instrument-Version 2 (MAYSI-2) is a brief screening tool used to identify youth in the juvenile justice system that are at-risk for mental health related difficulties. The MAYSI-2 was administered to 5,205 African American and Latino/a youth throughout Chicago, Illinois who were on probation and residing in the community. This study investigated differences (i.e., legal status, gender, age, race/ethnicity) in reporting of mental health symptoms and substance use on the MAYSI-2. Females scored above the clinical cutoffs more frequently than males and there were few differences found between diverted and adjudicated youth. Age comparisons revealed mixed results. Overall, youth in the current sample scored above the clinical cutoffs less often than youth in the MAYSI-2 norm reference groups. Nonetheless, during the first phase of this study the MAYSI-2 demonstrated effectiveness by accurately identifying a substantial portion of youth in need of mental health and/or substance abuse treatment

Exploring the impact of live music performances on the wellbeing of community-dwelling people living with dementia and their care partners

Background: Music-based initiatives cover a wide range of activity, including music therapy in either an individual or group capacity, choirs, orchestral performances, and apps on digital technology enabling people to engage with individual playlists. The impact of live music performances on the wellbeing of people living with dementia in the community is less well understood. Objective: To explore if attending a live music café impacts the wellbeing of community dwelling people living with dementia and their care partners. Study design: Twelve live music performances were hosted at a purpose refit facility at the authors’ institution, once a month between April 2018 and March 2019. Participants consenting to be part of the research included 7 people living with dementia, 7 care partners and 3 former care partners. Baseline semi-structured interviews explored the meaning of music and expectations of the upcoming music cafes. Dementia Care Mapping captured ‘in the moment’ experiences of each music cafe. Follow-up semi-structured focus groups explored the impact of music on wellbeing and if participant expectations had been met. Interviews were transcribed verbatim and analysed thematically. Main Findings: The findings demonstrate that attending the Music Café benefitted the selfreported and observable wellbeing of participants in three particular ways: first, by offering opportunities for peer support and a reduction in feelings of isolation through a shared love of music; second, creating opportunities to increase wellbeing through music ‘in the moment’ that can have lasting effects long after the event; third, group interaction with music meets an unmet need for meaningful musical experiences in supportive enabling environments. Conclusions and implications: Live music is a powerful medium to promote wellbeing for community dwelling people living with dementia and care partners. A ‘Music Café’ format promotes wellbeing through opportunities to interact with others in non-judgemental and supportive environments to experience a shared joy of music