Histopathological and molecular heterogeneity among individuals with dementia associated with Presenilin mutations

BACKGROUND: Mutations in the presenilin (PSEN) genes are associated with early-onset familial Alzheimer's disease (FAD). Biochemical characterizations and comparisons have revealed that many PSEN mutations alter gamma-secretase activity to promote accumulation of toxic Abeta42 peptides. In this study, we compared the histopathologic and biochemical profiles of ten FAD cases expressing independent PSEN mutations and determined the degradation patterns of amyloid-beta precursor protein (AbetaPP), Notch, N-cadherin and Erb-B4 by gamma-secretase. In addition, the levels of Abeta40/42 peptides were quantified by ELISA. RESULTS: We observed a wide variation in type, number and distribution of amyloid deposits and neurofibrillary tangles. Four of the ten cases examined exhibited a substantial enrichment in the relative proportions of Abeta40 over Abeta42. The AbetaPP N-terminal and C-terminal fragments and Tau species, assessed by Western blots and scanning densitometry, also demonstrated a wide variation. The Notch-1 intracellular domain was negligible by Western blotting in seven PSEN cases. There was significant N-cadherin and Erb-B4 peptide heterogeneity among the different PSEN mutations. CONCLUSION: These observations imply that missense mutations in PSEN genes can alter a range of key gamma-secretase activities to produce an array of subtly different biochemical, neuropathological and clinical manifestations. Beyond the broad common features of dementia, plaques and tangles, the various PSEN mutations resulted in a wide heterogeneity and complexity and differed from sporadic AD.Fil: Maarouf, Chera L.. Sun Health Research Institute; Estados UnidosFil: Daugs, Ian D.. Sun Health Research Institute; Estados UnidosFil: Spina, Salvatore. Universita Degli Studi Di Siena; Italia. Indiana University; Estados UnidosFil: Vidal, Ruben. Indiana University; Estados UnidosFil: Kokjohn, Tyler A.. Sun Health Research Institute; Estados Unidos. Midwestern University; Estados UnidosFil: Patton, R. Lyle. Sun Health Research Institute; Estados UnidosFil: Kalback, Walter M.. Sun Health Research Institute; Estados UnidosFil: Luehrs, Dean C.. Sun Health Research Institute; Estados UnidosFil: Walker, Douglas G.. Sun Health Research Institute; Estados UnidosFil: Castaño, Eduardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Beach, Thomas G.. Sun Health Research Institute; Estados UnidosFil: Ghetti, Bernardino. Indiana University; Estados UnidosFil: Roher, Alex E.. Sun Health Research Institute; Estados Unido

"Just Going Through the Motions.…": A Qualitative Exploration of Athlete Perceptions of Social Loafing in Training and Competition Contexts - Implications for Team Sport Coaches

Semi-structured interviews were conducted with twenty team sport athletes representing a range of different sports with the aim of investigating their views relating to social loafing in training and competition. General themes investigated and subsequent content analysis highlighted factors that promote or reduce the extent of social loafing. Determinants of self-loafing were grouped according to three distinct categories: Group processes; Task characteristics and Individual perceptions. Social loafing among others was perceived to be prevalent in both the training and competition scenarios with more examples of social loafing provided in the training situation. The signs of social loafing were grouped according to the following themes: Cognitive & Emotional, Behavioural, Communication and Player Intuition. Consequences of social loafing were found to be detrimental to the effort and performance of both the individual and the team. Athletes were also able to differentiate between perceived social loafing and the perceived use of ‘strategic rest’ in team sports. Implications for the coaching process are far reaching with the need to develop an effective team culture and to provide training sessions that are interesting, engaging and relevant

Reflection and the art of coaching: fostering high-performance in olympic ski cross

In preparation for the 2010 Vancouver Winter Olympic Games, the lead author engaged in systematic reflection in an attempt to implement coaching behaviours and create practice environments that promoted athlete development (psycho-social and physical performance). The research was carried out in relation to his work as head Ski Cross coach working with (primarily) three athletes in their quest for Olympic qualification and subsequent performance success in the Olympic Games. This project sought to examine coach-athlete interactions. Of particular interest were coach and athlete responses regarding the implementation of autonomy supportive coaching behaviours in a high context. Autonomy supportive coaching behaviours have previously been strongly associated with positive athlete psycho-social and performance outcomes, however, a paucity of research has examined its implementation in high-performance contexts. Through the use of participant ethnography, it was possible to gain considerable insights regarding athletes' perceptions of choice, implications of perceived athletic hierarchies, as well as cultural and experience-related influences on training and performance expectations

Robotic neurorehabilitation: a computational motor learning perspective

Conventional neurorehabilitation appears to have little impact on impairment over and above that of spontaneous biological recovery. Robotic neurorehabilitation has the potential for a greater impact on impairment due to easy deployment, its applicability across of a wide range of motor impairment, its high measurement reliability, and the capacity to deliver high dosage and high intensity training protocols

Philosophical Underpinnings of Coaching Practice Research

Research on coaching practice has mainly been undertaken through the disciplines of psychology and sociology. Very little scrutiny has been given to the philosophical underpinnings of these disciplinary positions and how they impact on research outputs in terms of descriptions and prescriptions. This article presents an overview of some of the most cited empirical research on coaching practice and shows how discipline and meta-theory have influenced a priori the results generated. Psychological approaches informed by scientism, and sociological approaches informed by interpretivism, present a dichotomized view of coaching practice, for example, concerning its relative simplicity and order. Yet these distinct disciplinary contributions remain important to the development of the field if it is understood that they contribute different layers of information and do different types of work. Once we have the meta-theoretical tools in place the results of this pluralism can be positioned and utilized. © 2013 Copyright National Association for Kinesiology in Higher Education (NAKHE)

First Dark Matter Search Results from the LUX-ZEPLIN (LZ) Experiment

The LUX-ZEPLIN (LZ) experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This Letter reports results from LZ's first search for Weakly Interacting Massive Particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross-sections for WIMP masses above 9 GeV/c$^2$. The most stringent limit is set at 30 GeV/c$^2$, excluding cross sections above 5.9$\times 10^{-48}$ cm$^2$ at the 90\% confidence level.Comment: 9 pages, 6 figures. See https://tinyurl.com/LZDataReleaseRun1 for a data release related to this pape

An exploration of the relationship between educational background and the coaching behaviours and practice activities of professional youth soccer coaches

This paper is closed access until 12 December 2019.Background and purpose: Despite the proliferation in recent years of higher education establishments offering tertiary-level study in the field of sports coaching, there is a lack of research into the impact of such courses on coaching practice. The behaviours employed and activities used by coaches during practice sessions is an area where one might expect to see such impact, indeed certain studies have tentatively noted the educational qualifications of coaches and suggested that this may play a role in the application of behaviours more aligned with player learning. The purpose of this study was therefore to compare youth soccer coaches with and without tertiary-level qualifications, examining their coaching behaviours and practice activities. Method: The participants were 10 male professional youth soccer coaches aged 24–55 with an average of 13 years coaching experience. Five of the coaches had completed undergraduate degree courses related to sport coaching. All of the coaches worked with players aged under 9 to under 18 in the youth academy of an English professional soccer club. Systematic observation of coach behaviour and practice activities was carried out using the Coach Analysis and Intervention System (Cushion et al. 2012), while follow-up interviews were used to elicit the coaches’ perceptions of, and rationale for, their behaviour. Findings: The observation data showed that graduate coaches used significantly more divergent questioning than non-graduate coaches, while the interview data revealed a general trend for graduate coaches to show greater self-awareness of behaviours and changes in behaviour between practice types. Graduate coaches also provided more comprehensive rationales, for example, seeing silence as a means of facilitating player decision-making as well as for observation. In contrast to previous research, sessions featured a higher proportion of playing form than training form activities and at over 20% of session duration, the ‘other’ practice state was a prominent feature of contact time with players. While some coaches saw ‘other’ as wasted time, graduate coaches identified this as an opportunity for group discussion and social interaction. The study adds to existing data about coach behaviours and practice activities, providing evidence that education background may indeed influence coaching practice

The impact of an "equal opportunities" ideological framework on coaches’ knowledge and practice

This study focuses upon UK professional coaches’ experiences of equity training and the impact of the conceptualisation of equity as a matter of equal opportunities on this education and subsequent coaching practice. The research employs a critical feminist approach to connect the ideological framing of gender equity by sporting organisations to coaches’ ability to understand, identify and manage issues of gender equity, equality and diversity. The discussions are based on interviews with four coaches, Jack, Peter, Charlotte and Tony, who had all recently undertaken equity training, and all of whom represented sports and different stages of the coaching pathway. The data highlights that seeing gender equity through an “equal opportunities” lens results in a narrow conceptualisation of such issues by coaches, fails to challenge dominant and discriminative ideologies, and does not enable coaches to address equity within their practices. Consequently, coaches struggle to understand the importance of and manage such issues. The participants’ experiences reveal that gender relations, intersected principally with religion and ethnicity, underpinned their everyday coaching practices. The findings illustrate the need for sporting organisations to redefine how they approach equality and equity and for a more sophisticated sociocultural educational programme for coaches