Search

TAR DNA binding protein (TDP-43, encoded by the TARDBP gene) has recently been shown to be associated with amyotrophic lateral sclerosis (ALS), but the early pathophysiological deficits causing impairment in motor function are unknown. Here we expressed the wild-type human gene (wtTARDBP) or the ALS mutation G348C (mulTARDBP) in zebrafish larvae and characterized their motor (swim-ming) activity and the structure and function of their neuromuscular junctions (NMJs). Of these groups only mutL4i?DBP larvae showed impaired swimming and increased motoneuron vulnerability with reduced synaptic fidelity, reduced quantal transmission, and more orphaned presynaptic and postsynaptic structures at the NMJ. Remarkably, all behavioral and cellular features were stabilized by chronic treatment with either of the L-type calcium channel agonists FPL 64176 or Bay K 8644. These results indicate that expression of mut-TARDBP results in defective NMJs and that calcium channel agonists could be novel therapeutics for ALS. [ABSTRACT FROM AUTHOR]

Abstract: Environmental temperature is one of the most important abiotic factors affecting insect behaviour; virtually all physiological processes, including those which regulate nervous system function, are affected. At both low and high temperature extremes insects enter a coma during which individuals do not display behaviour and are unresponsive to stimulation. We investigated neurophysiological correlates of chill and hyperthermic coma in Drosophila melanogaster. Coma resulting from anoxia causes a profound loss of K+ homeostasis characterized by a surge in extracellular K+ concentration ([K+]o) in the brain. We recorded [K+]o in the brain during exposure to both low and high temperatures and observed a similar surge in [K+]o which recovered to baseline concentrations following return to room temperature. We also found that rapid cold hardening (RCH) using a cold pretreatment (4°C for 2h; 2h recovery at room temperature) increased the peak brain [K+]o reached during a subsequent chill coma and increased the rates of accumulation and clearance of [K+]o. We conclude that RCH preserves K+ homeostasis in the fly brain during exposure to cold by reducing the temperature sensitivity of the rates of homeostatic processes. [Copyright &y& Elsevier]

This paper examines the wider social impacts of hosting the London 2012 Olympic Games and its 'legacy' ambitions in East London, emphasizing securitization as an inbuilt feature of the urban regeneration project. Drawing on extensive original empirical research, the paper analyses the modalities of Olympic safety and security practices within the Olympic Park itself and their wider impact, while also connecting this research to theorization and debates in urban sociology and criminology. In this complex setting, a raft of formal and informal, often subtle, regulatory mechanisms have emerged, especially as visions of social ordering focused on 'cleansing' and 'purifying' have 'leaked out' from the hyper-securitized 'sterilized' environment of the Olympic Park and become embedded within the Olympic neighbourhood. In such complex circumstances, applying Douglas' (1966) work on purity and danger to the spatial realm provides a key conceptual framework to understand the form and impact of such processes. The imposition of order can be seen to not only perform 'cleansing' functions, but also articulate multiple symbolic, expressive and instrumental roles. [ABSTRACT FROM AUTHOR]

This paper examines two nationally renowned football (il calcio) supporter groups located in the capital city of Rome, the centre of Italian political power. The first the Boys, followers of AS Roma, have been notoriously neo-fascist in character since 1972. The second, the Irriducibili who follow SS Lazio, a club that also play in Rome, have, since 1987, attained a notoriety based on toughness and violence. Defying historical, enmity-based logic the Boys and Irriducibili have shared since 1987 a neo-fascist ideology that has made the two curva (terraces) they occupy in the capital city's Olympic Stadium less hostile to each other. Indeed, the two groups have turned their antagonism against the State and the Italian police. These fan-protagonists exist in groups known throughout Italy as UllraS, the capital S being our neologism to define the neo-fascist-oriented fans and to differentiate them from the wider hardcore football supporters who are referred to as ultrd. The analysis herein focuses on these two UltraS entities and considers three central elements in the concept they promote of the 'true' UltraS: the principle of non omologazione (non-conformism), the Tradition versus Modernity opposition so crucial to the make-up of the UltraS cultural identity, and the attempt by such gatherings to live up to the ideal type of the Warrior. This research utilised the ethnographic method and involved the researcher 'being there' amongst the leading players of these two aforementioned groupings during various periods between 2001 and 2009. Those subject to academic inquiry are herein permitted to articulate their story and rationale. At the same time the researchers are concomitantly 'being here', seeking to infer the motivations of the members. [ABSTRACT FROM AUTHOR]

Neural tissue is particularly vulnerable to metabolic stress and loss of ion homeostasis. Repetitive stress generally leads to more permanent dysfunction but the mechanisms underlying this progression are poorly understood. We investigated the effects of energetic compromise in Drosophila by targeting the Na+/K+-ATPase. Acute ouabain treatment of intact flies resulted in subsequent repetitive comas that led to death and were associated with transient loss of K+ homeostasis in the brain. Heat shock pre-conditioned flies were resistant to ouabain treatment. To control the timing of repeated loss of ion homeostasis we subjected flies to repetitive anoxia while recording extracellular [K+] in the brain. We show that targeted expression of the chaperone protein Hsp70 in glial cells delays a permanent loss of ion homeostasis associated with repetitive anoxic stress and suggest that this is a useful model for investigating molecular mechanisms of neuroprotection. [ABSTRACT FROM AUTHOR]

Neural circuits are especially vulnerable to metabolic stress. The locust (Locusta migratoria) responds to anoxia by entering a coma during which neural and muscular systems shut down. During anoxic coma, arrest of the ventilatory central pattern generator is tightly correlated with an abrupt spreading depression (SD)-like increase in extracellular potassium concentration within the metathoracic neuropile. We examined the role of the AMP-activated protein kinase (AMPK), an evolutionarily conserved sensor of cellular energy status, in anoxia-induced ventilatory arrest and SD-like events in the locust. Perfusion of sodium azide (NaN3; mitochondrial toxin) induced SD, temporary coma, and profound changes in the ventilatory motor pattern characterized as a rapid rhythm before coma and a slower rhythm following recovery. AMPK activation using 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimicked the motor pattern changes induced by NaN3 but did not induce SD and coma. The effects of NaN3 on the ventilatory rhythm were reversed by perfusion of compound-C (AMPK inhibitor) or glucose, and the effects of AICAR were also reversed by compound-C, confirming the modulatory roles of AMPK and energy status. Ouabain-induced recurring SD was suppressed by inhibition of AMPK and exacerbated by its activation. We show that the motor pattern changes induced by metabolic stress are not the result of SD alone, but that AMPK is necessary and sufficient for these changes and that AMPK activity strongly influences susceptibility to SD. [ABSTRACT FROM AUTHOR]

Despite considerable research attention focused on mechanisms underlying neural spreading depression (SD), because of its association with important human CNS pathologies, such as stroke and migraine, little attention has been given to explaining its occurrence and regulation in invertebrates. In the locust metathoracic ganglion (MTG), an SD-like event occurs during heat and anoxia stress, which results in cessation of neuronal output for the duration of the applied stress. SD-like events were characterized by an abrupt rise in extracellular potassium ion concentration ([K+]o ) from a baseline concentration of ~8 to >30 mM, which returned to near baseline concentrations after removal of the applied stress. After return to baseline [K+]o, neuronal output (ventilatory motor pattern activity) from the MTG recovered. Unlike mammalian neurons, which depolarize almost completely during SD, locust neurons only partially depolarized. SD-like events in the locust CNS were suppressed by pharmacological inhibition of the nitric oxide/cyclic guanosine monophosphate/ protein kinaseG(NO/cGMP/PKG) pathway and were exacerbated by its activation. Also, environmental stressors such as heat and anoxia increased production of nitric oxide in the locust CNS. Finally, for the intact animal, manipulation of the pathway affected the speed of recovery from suffocation by immersion under water. We propose that SD-like events in locusts provide an adaptive mechanism for surviving extreme environmental conditions. The highly conserved nature of the NO/cGMP/PKG signaling pathway suggests that it may be involved in modulating SD in other organisms, including mammals. [ABSTRACT FROM AUTHOR]

Classroom instruction continues to change dramatically with new technology and pedagogy. Faculty aspire to develop innovative programs and creative education while seeking effective teaching strategies that capitalize on emerging technology and invoke student interest and involvement. Research shows that student involvement, hands-on projects, and teamwork are successful pedagogical approaches (Kayes, Kayes, & Kolb, 2005; McKeachie 1994; Passman 2001). This paper describes a creative project for students that showcases technology and student involvement. Additionally, the assignment is consistent with the seven principles for good practice in higher education (Chickering & Gamson, 1987) and provides desired outcomes to business education such as business fundamentals, critical thinking, teamwork, and technology skills. Students prepare a team-based research presentation on a topic that incorporates a student produced podcast. Students produce and share a podcast in which they interview an expert or knowledgeable individual in the research topic area. By producing podcasts, students have the opportunity to research and analyze information, communicate effectively, and incorporate the opinions of experts in a cutting-edge way. Producing and comparing their own work to that of others can give students a valuable perspective on their own abilities and inspire them to try new ideas or techniques. Software programs and computers make it easier to record and edit audio and video programs than in the past. During the course of the project, students are exposed to Audacity, Windows Movie Maker, Visio, FreeMind, new search engines, HTML and RSS code, FTP, and the operation of digital and audio recorders. The instructor has the option of providing access to the podcast to a course management system such as Blackboard; making each team's podcast available for campus consumption by uploading the podcast to a restricted website; or providing unrestricted access by posting the podcast to iTunes or similar podcast subscription service. We utilized an evaluation questionnaire to assess the effectiveness of the project. From the students' perspective, the project was very effective in meeting educational objectives. The design of the project utilizes the seven principles for good practice in higher education, and skills students need to produce the podcast are consistent with desired learning outcomes. Student produced podcasts provide the instructor an opportunity to build a library of podcasts, which then can be integrated into future classes. The result is a win-win opportunity for student and faculty alike. [ABSTRACT FROM AUTHOR]

Over the past two decades the link - perceived and actual - between political extremism and football fans has been the subject of academic, political, and policing debate. It is not rare to witness manifestations of intolerance and ideological statements referring to regional, national and international issues at football stadia. In Italian football stadia, political representation has been evident for decades; politics has been integral to all realms of Italian society and culture since the origin of the nation. As one of the most significant Italian cultural practices, football has not been an exception. This combination of theory and action inspires thousands of young male football supporters. The football stadium might thus be interpreted as a twenty-first century social Agora, where political opinions - otherwise ghettoized in society - can be freely expressed in pursuit of a wider consensus. This paper explores the under-researched milieu of neo-fascist ideology as displayed in contemporary Italian football stadia. Contributing original material and employing as conceptual frameworks the New Consensus Theory on fascism and the works of Julius Evola and Georges Sorel, this analysis hypothesizes that the neo-fascist tenets manifested by the ideologically-oriented 'ultras' fan groups, may be understood as both a consequence of, and a resistance against the dominant socio-cultural and political values of contemporary Italy. The research conducted between 2003-2007 sought to evaluate two internationally renowned ultras groups located in the Italian capital of Rome: the Boys of AS Roma and the Irriducibili of SS Lazio who enact their performances on their respective 'curve' [football terraces] of the city's Olympic stadium. Utilizing the ethnographic method, unique access was achieved in a notoriously difficult research milieu bringing the researcher into the social-cultural world of the participants and to the echelons of the extra-parliamentary Italian far right. Research sought to uncover the groups' social interactions, values, and political beliefs, as a way of contributing to an understanding of both the Italian ultras of the twenty-first century and indeed the wider political milieu of the modern nation-state of Italy. [ABSTRACT FROM AUTHOR]

A correction to this paper has been published: https://doi.org/10.1007/s13311-021-01061-2 [ABSTRACT FROM AUTHOR]

This paper describes empirical research amongst hooligans. Such research has not always been valued. The significant factor in hooligan behaviour may be asserted to be the generation of violence in the lower working class and its dissemination amongst football fans. It is commonly asserted that hooligans operate in well-organized groups. It is argued here that such assertions need to be based on better evidence. A detailed account is given of the behaviour of a notorious group of fans and its key individuals. This shows that the 'hard core' fans were distinguished from others only by greater dedication to football and their club; they had a potentiality for violence but only of the low level kind that many others shared; they were more often involved simply because they went to more matches; they lacked organization. Nevertheless outsiders were, not unreasonably, sure they were a violent, organized group. This casts doubt on similar beliefs held about other groups unless beliefs are well substantiated. Detailed ethnography is valuable because it helps to sort out the nature of the 'hooligan' problem that requires to be theorized. [ABSTRACT FROM AUTHOR]

This study employs a cognitive response approach using nod-directive probes rather than direct questions to assess the effects of advertising knowledge and the presence of a cue on thoughts produced by 9 to 10-year-old children while watching commercials. The number of counterargument produced indicates children's use of cognitive defenses. The study found that advertising knowledge did not result in increased counterarguments against advertisements unless a cue was present to activate that knowledge. Direct questions (as opposed to non-directive probes themselves appear to activate advertising knowledge, thus overestimating children's actual use of cognitive defenses. [ABSTRACT FROM AUTHOR]

Lymphoblastoid cells were cultured from two Herpesvirus saimiri (HVS) inoculated white-lipped marmosets and from one HVS-inoculated owl monkey. Cells from all three animals grew clumped in suspension. The cells from both species were diploid in chromo-some number and showed no unusual chromosomal abnormalities. The marmoset cell line examined was chimaeric. The marmoset cells lacked HSV-associated antigens as determined by immunofluorescence, and no evidence for the presence of virus was found by either infectivity assays or electron microscopy. Cocultivation of these cells with Vero cells resulted in cytopathology and the recovery of complete, infectious virus. The owl monkey lymphoid cells were positive to a small degree for both viral antigens and infectivity. The cells were resistant to rechallenge with HVS. Cocultivation of these cells with Vero cells led to the development of cytopathology and an increased yield of virus. [ABSTRACT FROM AUTHOR]

Most studies of the organizational buying process assume that buyers acquire and use information "prosocially "-to make better decisions and promote their company's welfare. The authors propose, however that demands to account for their behavior causes organizational buyers to also gather and use information for political purposes-to protect their own self-interest The authors present the results of an empirical study that investigates the extent to which four types of accountability-informal, official, process, and decision accountability-result in political (or symbolic) information search and prosocial information analysis by organizational buyers. Study findings suggest that buyers accountable to superiors and those accountable to subordinates or peers engage in more symbolic information search. Buyers accountable for their decision-making process analyze information more extensively. Surprisingly, buyers accountable for decision outcomes neither search for symbolic information nor analyze information more extensively. [ABSTRACT FROM AUTHOR]

Though there is compelling evidence that de-innervation of neuromuscular junctions (NMJ) occurs early in amyotrophic lateral sclerosis (ALS), defects arising at synapses in the spinal cord remain incompletely understood. To investigate spinal cord synaptic dysfunction, we took advantage of a zebrafish larval model and expressed either wild type human TARDBP (wtTARDBP) or the ALS-causing G348C variant (mutTARDBP). The larval zebrafish is ideally suited to examine synaptic connectivity between descending populations of neurons and spinal cord motoneurons as a fully intact spinal cord is preserved during experimentation. Here we provide evidence that the tail-beat motor pattern is reduced in both frequency and duration in larvae expressing mutTARDBP. In addition, we report that motor-related synaptic depolarizations in primary motoneurons of the spinal cord are shorter in duration and fewer action potentials are evoked in larvae expressing mutTARDBP. To more thoroughly examine spinal cord synaptic dysfunction in our ALS model, we isolated AMPA/kainate-mediated glutamatergic miniature excitatory post-synaptic currents in primary motoneurons and found that in addition to displaying a larger amplitude, the frequency of quantal events was higher in larvae expressing mutTARDBP when compared to larvae expressing wtTARDBP. In a final series of experiments, we optogenetically drove neuronal activity in the hindbrain and spinal cord population of descending ipsilateral glutamatergic interneurons (expressing Chx10) using the Gal4-UAS system and found that larvae expressing mutTARDBP displayed abnormal tail-beat patterns in response to optogenetic stimuli and augmented synaptic connectivity with motoneurons. These findings indicate that expression of mutTARDBP results in functionally altered glutamatergic synapses in the spinal cord. [ABSTRACT FROM AUTHOR]