Inelastic collisions of ultra-cold heteronuclear molecules in an optical trap

Ultra-cold RbCs molecules in high-lying vibrational levels of the a$^3\Sigma^+$ ground electronic state are confined in an optical trap. Inelastic collision rates of these molecules with both Rb and Cs atoms are determined for individual vibrational levels, across an order of magnitude of binding energies. A simple model for the collision process is shown to accurately reproduce the observed scattering rates

Chronic Cellular Imaging of Entire Cortical Columns in Awake Mice Using Microprisms

SummaryTwo-photon imaging of cortical neurons in vivo has provided unique insights into the structure, function, and plasticity of cortical networks, but this method does not currently allow simultaneous imaging of neurons in the superficial and deepest cortical layers. Here, we describe a simple modification that enables simultaneous, long-term imaging of all cortical layers. Using a chronically implanted glass microprism in barrel cortex, we could image the same fluorescently labeled deep-layer pyramidal neurons across their entire somatodendritic axis for several months. We could also image visually evoked and endogenous calcium activity in hundreds of cell bodies or long-range axon terminals, across all six layers in visual cortex of awake mice. Electrophysiology and calcium imaging of evoked and endogenous activity near the prism face were consistent across days and comparable with previous observations. These experiments extend the reach of in vivo two-photon imaging to chronic, simultaneous monitoring of entire cortical columns.Video Abstrac

Co-Expression of miRNA Targeting the Expression of PERK, but Not PKR, Enhances Cellular Immunity from an HIV-1 Env DNA Vaccine

Small non-coding micro-RNAs (miRNA) are important post-transcriptional regulators of mammalian gene expression that can be used to direct the knockdown of expression from targeted genes. We examined whether DNA vaccine vectors co-expressing miRNA with HIV-1 envelope (Env) antigens could influence the magnitude or quality of the immune responses to Env in mice. Human miR-155 and flanking regions from the non-protein encoding gene mirhg155 were introduced into an artificial intron within an expression vector for HIV-1 Env gp140. Using the miR-155-expressing intron as a scaffold, we developed novel vectors for miRNA-mediated targeting of the cellular antiviral proteins PKR and PERK, which significantly down-modulated target gene expression and led to increased Env expression in vitro. Finally, vaccinating BALB/c mice with a DNA vaccine vector delivering miRNA targeting PERK, but not PKR, was able to augment the generation of Env-specific T-cell immunity. This study provides proof-of-concept evidence that miRNA effectors incorporated into vaccine constructs can positively influence vaccine immunogenicity. Further testing of vaccine-encoded miRNA will determine if such strategies can enhance protective efficacy from vaccines against HIV-1 for eventual human use

Induction of GADD34 Is Necessary for dsRNA-Dependent Interferon-β Production and Participates in the Control of Chikungunya Virus Infection

Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events. The dsRNA-dependent protein kinase (PKR) phosphorylates translation initiation factor 2-alpha (eIF2α) and inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN and other cytokines. We demonstrate that the phosphatase-1 cofactor, growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), an important component of the unfolded protein response (UPR), is absolutely required for type I-IFN and IL-6 production by mouse embryonic fibroblasts (MEFs) in response to dsRNA. GADD34 expression in MEFs is dependent on PKR activation, linking cytosolic microbial sensing with the ATF4 branch of the UPR. The importance of this link for anti-viral immunity is underlined by the extreme susceptibility of GADD34-deficient fibroblasts and neonate mice to Chikungunya virus infection

Improving care for people with dementia: development and initial feasibility study for evaluation of life story work in dementia care

Background: Improving dementia care quality is an urgent priority nationally and internationally. Life story work (LSW) is an intervention that aims to improve individual outcomes and care for people with dementia and their carers. LSW gathers information and artefacts about the person, their history and interests, and produces a tangible output: the ‘life story’. Objective: To establish whether or not full evaluation of LSW was feasible. Design: Mixed-methods feasibility study. Methods: In-depth interviews and focus groups explored experiences of LSW and best practice with people with dementia, family members and dementia care staff. A systematic review explored best practice and theories of change for LSW. These stages helped to identify the outcomes and resources to explore in the feasibility study. A representative sample survey of health and social care dementia care providers in England established LSW practice in different settings. A survey of a self-selected sample of family members of people with dementia explored how LSW is experienced. Two small outcome studies (stepped-wedge study in six care homes and pre-test post-test study in inpatient specialist dementia care wards) explored the feasibility of full evaluation of LSW in these settings. Settings: Survey: generalist and specialist care homes; NHS dementia care settings; and community dementia services. Feasibility study: care homes and NHS inpatient dementia care wards. Participants: NHS and social care services, people with dementia, family carers, care home staff and NHS staff. Interventions: LSW. Main outcome measures: Spread of LSW and good practice, quality of life (QoL) for the person with dementia and carers, relationships between people with dementia and family carers, staff attitudes about dementia, staff burnout, resource use and costs. Review methods: Narrative review and synthesis, following Centre for Review and Dissemination guidelines. Results: Good practice in LSW is identifiable, as are theories of change about how it might affect given outcomes. Indicators of best practice were produced. LSW is spreading but practice and use vary between care settings and are not always in line with identified good practice. Two different models of LSW are evident; these are likely to be appropriate at different stages of the dementia journey. The feasibility study showed some positive changes in staff attitudes towards dementia and, for some people with dementia, improvements in QoL. These may be attributable to LSW but these potential benefits require full evaluation. The feasibility work established the likely costs of LSW and highlighted the challenges of future evaluation in care homes and inpatient dementia care settings. Limitations: There was insufficient evidence in the literature to allow estimation of outcome size. We did not carry out planned Markov chain modelling to inform decisions about carrying out future evaluation because of the dearth of outcome data in the literature; low levels of data return for people with dementia in the hospital settings; lack of detected effect for most people with dementia; and questions about implementation in the research settings. Conclusions: LSW is used across different health and social care settings in England, but in different ways, not all of which reflect ‘good practice’. This large, complex study identified a wide range of challenges for future research, but also the possibility that LSW may help to improve care staff attitudes towards dementia and QoL for some people with dementia. Future work: Full evaluation of LSW as an intervention to improve staff attitudes and care is feasible with researchers based in or very close to care settings to ensure high-quality data collection. Funding: The National Institute for Health Research Health Services and Delivery Research programme. Keywords

CNS Infiltration of Peripheral Immune Cells: D-Day for Neurodegenerative Disease?

While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as “immune privilege,” it is now clear that immune responses do occur in the CNS—giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue

Theme and Variations: Creative Improvisation in African Textiles

The Euro-American textile patterning vocabulary focusses on compartmentalization and symmetry. We describe textile design schemes as repeats; and as with many aspects of our lives, we divide our expressions into neat cubicles. The art historian, Meyer Shapiro, who wrestled with this cultural trait expressed it this way: Hardening of the categories causes art disease. Yet, for many art-producing cultures there is scant division between the working world and the spiritual, the procurement of food and maintenance of order; relating history and group entertainment. Art is life. The function of artistic structure and the tenets of life are often interwoven. Theme and variation takes on a particular richness among Subsaharan groups. In myth and music, as well as in textile design rhythmic placement, improvisation and layering of information are combined with great sophistication

Amongst the shadows of mineralized mountains: resource-making and social becoming in the Peruvian Andes

Since the 1990s, the adoption of the extractive imperative in Peru, while leading to unprecedented economic growth, has simultaneously entailed the proliferation of local contestation at the point source of mineral exploitation. To date, academic attention on ‘conflictos mineros’ (mining conflicts) has been dominated by interpretations of political economy which shroud local realities amongst the implicit assumptions of ‘isolation’ and ‘alterity’. Ethnographic interventions on contemporary mining in Peru have lagged behind the explanatory rush. This dissertation, based on 15 months of fieldwork in the communities which surround the Bambas copper mine, attempts to shift and destabilize scholastic presumption. Grounding its theoretical trajectory in progressive imaginaries of social mobility (the ‘search for a better life’), the thesis attempts to dissolve the dominant prisms of ‘peasant’ and ‘indigenous’ communities to elucidate the complex and, at times, contradictory outcomes of mining as practiced in southern Peru. Resource-making, it is argued, interjects upon fraught histories of marginalization, activating latent desires for social becoming. Over time, however, the maturation of mining, from exploration to eventual low-labor production, unfurls stark discordances between development’s image and reality. Communities and individuals are forced to navigate this shifting social terrain, interpreting millennial moral orders, developing alternative projects for the ‘better life’, and, ultimately, ‘waiting’ for imagined futures that are increasingly threatened by precarity. These crises in social becoming produce unintended outcomes, even amongst the ‘responsible’ precepts of ‘modern mining’. Accordingly, CSR works to govern expectation and corporate entanglements with shadowed communities. Environmental regulation creates complex and insecure relations between toxic legacies and endurance. While indigenous legal precepts transform through the friction of travel and contact to eventually assemble artisanal mining ventures. The overarching empirics move with and beyond conventional conceptions of Andean peoples and corporate interventions to demonstrate festering frustrations with development trajectories and continuous maneuvering within them. </p

What Are Your Plans For Next Year?: An Assessment of The Career Decision-Making Self-Efficacy and Career Maturity of Adolescents With Hearing Loss

The purpose of this research was to analyze the career decision-making and self-efficacy of adolescents age 15-19 years old who are deaf and hard of hearing, who attend or have attended mainstream school settings and who primarily use auditory verbal communication. This investigation endeavored to determine how much self-efficacy, or confidence, these individuals report having in various career competencies and if these individual’s level of career maturity is influenced by a hearing difference. Participants were contacted nationwide, and included in the survey protocol was the Career Decision-Making Self Efficacy Scale and the Career Maturity Inventory, Form-C. Results of this research suggest adolescents with hearing loss demonstrate moderate to high confidence in career decision making self-efficacy. Scores on the Career Maturity Inventory also approximated norms of students without hearing loss. Individual results varied on items pertaining to hearing loss in school, preparation for future jobs/careers and worry about hearing accommodations/technology and further research is suggested on this topic of career self efficacy and career decision making for populations with disabilities