What is the relationship between the situated learning of Unarmed Civilian Protection workers and gendered power dynamics?

This study used a mixed methods, grounded theory approach to investigate the situated learning of Unarmed Civilian Protection (UCP) workers and its relationship to hegemonic gender regimes. It reviews the everyday situated learning of UCP workers in the context of and structures gender and race. UCP is understood as a unique ‘Community of Practice’ subordinate to and nested within the overarching humanitarian infrastructure. The definition and contestation of UCP by different workers and related, fluid dynamics of complicity with and resistance to structural power are explored. The unique contributions to knowledge that this thesis makes are in three key areas: 1/ Firstly this study represents the first, hopefully of many forays into studying UCP via a new critical framing which situates the UCP practice in explicit relation to feminism, gender, identity and other subjectivities, 2/ Within this framing, and especially in the use of feminist care ethics, we can observe how care not only supports and makes possible knowledge creation and sharing, but is itself a form of social reproduction that sustains and ‘makes’ UCP. The differential distribution of the burden of care and knowledge creation in UCP teams demands further attention. This recognition of the centrality of Care to UCP sheds new light on how UCP is practiced and experienced differently by not only men and women but by people of numerous intersecting subjectivities. 3/ Finally this thesis indicates that greater attention to the intersectionality of identities within the UCP community is essential to future scholarship and action around this practice; especially the importance of the eldership of older, more experienced men and women from the Global South, and the embodied knowledge that these elders recognize, carry and share with peers. The findings of this study indicate ways in which UCP practice affects personal behavior, promotes critical reflection on questions of power and identify and that facilitates a diverse range of agency in their gender performance. However UCP is subject to the same structural challenges as other humanitarian work, including the privileging of certain types of white, Eurocentric masculinities and femininities. Unique components of the practice invert the masculinist security paradigm and foreground a radical ethics of care and collective knowing. However UCP practice currently exhibits only limited resistance to the disciplinary power of the technocratic ‘security-development nexus’. This thesis indicates the importance of further research and practice which attends to the intersectionality of identities within the UCP community; especially the importance of the eldership of experienced practitioners. Recommendations include greater attention to and diversity of learning approaches including mentorship and more concerted transnational exchange between practitioners in different countries and continents. These interventions, combined with organizational focusses on retention will consolidate and further the possibilities of agencies from UCP workers that actively embody resistance to dominative hegemonic regimes that normalize colonial, militarized ideals of gender

The development of the Soviet Navy since World War II

This thesis is a study of the Soviet Navy since World War II. The fact that the Soviet Navy has, in the past thirty years, been transformed from a position of comparative naval insignificance to a naval power second only to that of the United States of America is, clearly, the most important naval development of the post war world and as such deserves description, explanation and evaluation. The account which follows seeks to describe this development. and to show to what extent it has - (a) been brought about by changes in Soviet strategic assessments of the importance of sea power; (b) altered the role of the Navy in Soviet military doctrine as enunciated by Soviet political, military and naval leaders; (c) provided the Soviet Navy with the means to carry out the roles assigned to it at various periods in the post war era. It also indicates the extent to which the geographical position of the Fleet areas and the limitations imposed on any branch of the armed services by the priorities of the political leadership have influenced the Navy's development and its capabilities. Chapters 1 and 2 establish the significance of the geographic handicaps impose0. on the Soviet Navy and provide an appreciation of the role of the navy in Soviet military doctrine prior to and in the immediate post World War II period. This is essential background for what follows. No sensible evaluation of the strength of the Soviet Navy can beattempted without appreciating the fact that its total strength is allocated to four widely dispersed fleet areas each of which has its point of egress to the high seas flanked by foreign powers belonging to adverse alliance systems. Equally no account of the changing roles of the Soviet Navy or explanation of its growth in terms of numbers or types of vessels available is complete without the realisation that, historically,primacy has been afforded the ground forces, with the navy playing the subordinate role of "loyal assistant". The extent to which this perception of the navy, as essentially a subordinate arm of service, has changed, both within the navy, within other branches of the armed services and within the political leadership of the Soviet Union, is a major concern of this thesis

Human Stem Cells for Modeling Amyotrophic Lateral Sclerosis Disease Mechanisms and Modifiers

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor system. Although ALS has been extensively studied in post-mortem patient samples and animal models, there are currently no very effective treatments and there is no cure. One reason for the lack of treatment options in ALS may stem from the inaccessibility of living human motor neurons for use in disease research and subsequent therapeutic target validation. Recent developments in the field of stem cell biology can potentially provide access to living human motor neurons from individual ALS patients. It is now possible to derive induced pluripotent stem cells (iPS cells) from the somatic tissues of ALS patients and then to differentiate these iPS cells into motor neurons with the precise genetic makeup of the donor patient (iPS-MNs). Before iPS-MNs can be put to productive use, however, the iPS system as a whole must be validated as a reliable source of motor neurons with characteristics that closely resemble their endogenous or hES-derived counterparts. This thesis will first address a series of issues relating to the validation of iPS cells as a reliable source of motor neurons a then move on to expression profiling studies aimed at identifying a transcriptional signature of ALS in iPS-MNs. I will first describe a collaborative study aimed at determining whether or not iPS cells are as useful as ES cells for the production of motor neurons. By comparing motor neuron differentiation efficiency across a panel of 6 ES lines and 16 iPS lines, we demonstrated that iPS cells are equally capable of producing electrophysiologically active motor neurons as ES cells. Moreover, both ALS and control iPS lines produce motor neurons with equal efficiency, suggesting that iPS cells will be useful in the production of ALS iPS-MNs for disease research. In addition, our results identify some of the variables that contribute to differentiation efficiency, including donor identity and individual iPS/ES line identity. The following section will serve to provide a deeper molecular and electrophysiological understanding of human stem cell-derived motor neurons. I first generated expression profiles from purified hES-MNs to identify potential motor neuron-specific surface markers as well as maturational changes occurring in motor neurons in vitro. Using calcium imaging techniques, I then demonstrated that iPS-MNs behave functionally similarly to ES-MNs and described culture-wide rhythmic depolarizations that are likely influencing multiple properties of iPS-MNs. After characterizing the iPS-MN culture system, I made a first attempt at defining the transcriptional phenotypes of ALS in iPS-MNs. This work relied on the use of a motor neuron-specific lentiviral reporter that I developed to isolate and transcriptionally profile iPS-MNs from two control iPS lines and four ALS iPS lines. I show evidence of significant transcriptional differences between motor neurons isolated from ALS lines and those from control patients. These differences may in the future help to define ALS-specific phenotypes. Lastly, I conducted a meta-analysis comparing transcriptional changes in ALS iPS-MNs to those in existing models of ALS and identified some common stress-related features of ALS in iPS-MNs. In order to form new hypotheses about what sorts of individual patient-specific phenotypes may be present in iPS-MNs, I will then utilize published expression profiles from post-mortem ALS patient motor neurons to identify a previously-overlooked class of genes that exhibit expression levels highly correlated with individual age at ALS onset. This group of 43 onset-correlated genes contains many members with known or hypothesized relationships to neurodegenerative disease. I discuss how onset-correlated genes may function as disease-modifiers or biomarkers and design experiments to investigate these possibilities. Taken together, the work in this thesis will lay the foundations for developing a human iPS-based model of ALS and point toward numerous avenues of future investigation

Stem Cells in the Nervous System

Given their capacity to regenerate cells lost through injury or disease, stem cells offer new vistas into possible treatments for degenerative diseases and their underlying causes. As such, stem cell biology is emerging as a driving force behind many studies in regenerative medicine. This review focuses on the current understanding of the applications of stem cells in treating ailments of the human brain, with an emphasis on neurodegenerative diseases. Two types of neural stem cells are discussed: endogenous neural stem cells residing within the adult brain and pluripotent stem cells capable of forming neural cells in culture. Endogenous neural stem cells give rise to neurons throughout life, but they are restricted to specialized regions in the brain. Elucidating the molecular mechanisms regulating these cells is key in determining their therapeutic potential as well as finding mechanisms to activate dormant stem cells outside these specialized microdomains. In parallel, patient-derived stem cells can be used to generate neural cells in culture, providing new tools for disease modeling, drug testing, and cell-based therapies. Turning these technologies into viable treatments will require the integration of basic science with clinical skills in rehabilitation

Novel Compound Heterozygous Mutations Expand the Recognized Phenotypes of \u3cem\u3eFARS2\u3c/em\u3e-linked Disease

Mutations in mitochondrial aminoacyl-tRNA synthetases are an increasingly recognized cause of human diseases, often arising in individuals with compound heterozygous mutations and presenting with system-specific phenotypes, frequently neurologic. FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase (mtPheRS), perturbations of which have been reported in 6 cases of an infantile, lethal disease with refractory epilepsy and progressive myoclonus. Here the authors report the case of juvenile onset refractory epilepsy and progressive myoclonus with compound heterozygous FARS2 mutations. The authors describe the clinical course over 6 years of care at their institution and diagnostic studies including electroencephalogram (EEG), brain magnetic resonance imaging (MRI), serum and cerebrospinal fluid analyses, skeletal muscle biopsy histology, and autopsy gross and histologic findings, which include features shared with Alpers-Huttenlocher syndrome, Leigh syndrome, and a previously published case of FARS2 mutation associated infantile onset disease. The authors also present structure-guided analysis of the relevant mutations based on published mitochondrial phenylalanyl transfer RNA synthetase and related protein crystal structures as well as biochemical analysis of the corresponding recombinant mutant proteins

The c-Rel Subunit of NF-κB Regulates Epidermal Homeostasis and Promotes Skin Fibrosis in Mice

The five subunits of transcription factor NF-κB have distinct biological functions. NF-κB signaling is important for skin homeostasis and aging, but the contribution of individual subunits to normal skin biology and disease is unclear. Immunohistochemical analysis of the p50 and c-Rel subunits within lesional psoriatic and systemic sclerosis skin revealed abnormal epidermal expression patterns, compared with healthy skin, but RelA distribution was unaltered. The skin of Nfkb1−/− and c-Rel−/− mice is structurally normal, but epidermal thickness and proliferation are significantly reduced, compared with wild-type mice. We show that the primary defect in both Nfkb1−/− and c-Rel−/− mice is within keratinocytes that display reduced proliferation both in vitro and in vivo. However, both genotypes can respond to proliferative stress, with 12-O-tetradecanoylphorbol-13-acetate–induced epidermal hyperproliferation and closure rates of full-thickness skin wounds being equivalent to those of wild-type controls. In a model of bleomycin-induced skin fibrosis, Nfkb1−/− and c-Rel−/− mice displayed opposite phenotypes, with c-Rel−/− mice being protected and Nfkb1−/− developing more fibrosis than wild-type mice. Taken together, our data reveal a role for p50 and c-Rel in regulating epidermal proliferation and homeostasis and a profibrogenic role for c-Rel in the skin, and identify a link between epidermal c-Rel expression and systemic sclerosis. Modulating the actions of these subunits could be beneficial for treating hyperproliferative or fibrogenic diseases of the skin

Online health communities

Abstract Online health communities provide a means for patients and their families to learn about an illness, seek and offer support, and connect with others in similar circumstances. They are supported by a variety of technologies (e.g., email lists, forums, chat rooms) and are hosted by patients, advocacy groups, medical organizations, and corporations. They raise difficult design challenges because of the wide variability of members' medical expertise, the severity of problems due to misinformation, and the need for emotional support. The importance of on-line health communities is evidenced by their popularity, as well as the significant impact they have on the lives of their members. This Special Interest Group (SIG) will explore current trends in online health communities, as well as discuss the socio-technical design challenges and opportunities that they afford

Synaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer's Disease Brain

Alzheimer's disease (AD) is defined by the presence of intraneuronal neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau aggregates as well as extracellular amyloid-beta plaques. The presence and spread of tau pathology through the brain is classified by Braak stages and thought to correlate with the progression of AD. Several in vitro and in vivo studies have examined the ability of tau pathology to move from one neuron to the next, suggesting a “prion-like” spread of tau aggregates may be an underlying cause of Braak tau staging in AD. Using the HEK293 TauRD-P301S-CFP/YFP expressing biosensor cells as a highly sensitive and specific tool to identify the presence of seed competent aggregated tau in brain lysate—i.e., tau aggregates that are capable of recruiting and misfolding monomeric tau—, we detected substantial tau seeding levels in the entorhinal cortex from human cases with only very rare NFTs, suggesting that soluble tau aggregates can exist prior to the development of overt tau pathology. We next looked at tau seeding levels in human brains of varying Braak stages along six regions of the Braak Tau Pathway. Tau seeding levels were detected not only in the brain regions impacted by pathology, but also in the subsequent non-pathology containing region along the Braak pathway. These data imply that pathogenic tau aggregates precede overt tau pathology in a manner that is consistent with transneuronal spread of tau aggregates. We then detected tau seeding in frontal white matter tracts and the optic nerve, two brain regions comprised of axons that contain little to no neuronal cell bodies, implying that tau aggregates can indeed traverse along axons. Finally, we isolated cytosolic and synaptosome fractions along the Braak Tau Pathway from brains of varying Braak stages. Phosphorylated and seed competent tau was significantly enriched in the synaptic fraction of brain regions that did not have extensive cellular tau pathology, further suggesting that aggregated tau seeds move through the human brain along synaptically connected neurons. Together, these data provide further evidence that the spread of tau aggregates through the human brain along synaptically connected networks results in the pathogenesis of human Alzheimer's disease

A 44-year-old man with eye, kidney, and brain dysfunction

Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare, autosomal dominant condition caused by mutations of the three-prime repair exonuclease-1 (TREX1). The phenotypic expressions range from isolated retinal involvement to varying degrees of retinopathy, cerebral infarction with calcium depositions, nephropathy, and hepatopathy. We report a case of RVCL caused by a novel TREX1 mutation. This patient’s multisystem presentation, retinal involvement interpreted as “retinal vasculitis”, and improvement of neuroimaging abnormalities with dexamethasone led to the accepted diagnosis of a rheumatologic disorder resembling Behçet’s disease. Clinicians should consider RVCL in any patient with retinal capillary obliterations associated with tumefactive brain lesions or nephropathy