Mitochondrial DNA regulates TNF-alpha mRNA stability

Sepsis is defined as potentially fatal systemic inflammation, caused by an infection. It is the leading cause of ICU mortality and the 10th leading cause of death in the United States. Several models exist to mimic this disorder, and have demonstrated differential mortality rates between the models as well as the individual animals. Previous studies have shown that elevated levels of plasma mitochondrial DNA (mtDNA) correlated with mortality in septic patients, and cell-free mitochondrial DNA can elicit toll-like receptor mediated immune responses similar to LPS-mediated septicemia. However, the role of mtDNA in the pathophysiology sepsis is still unknown. The focus of this study was to create sepsis in a mouse model using the murine Cecal Ligation and Puncture (CLP) model, and measure plasma mtDNA levels. After CLP was performed on experimental mice, blood plasma was collected 24 hours later. Elevated amounts of circulating mtDNA were detectable in the plasma using real time PCR and cytochrome B2 as a marker of mitochondria. These data were correlated with plasma IL-6 levels, which were used to predict mortality within 5 days of CLP to stratify mice into two populations of those predicted to live or die following the procedure. We also aimed to investigate the effect of mtDNA and mitochondrial debris on naïve mouse macrophages in an in vitro study of the regulation of inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β). In order to observe the effects of mtDNA on murine macrophages, mitochondria was purified from mouse liver and used to stimulate these cells alongside positive control, LPS. Stimulation with mtDNA and mitochondrial debris resulted in increased levels of TNF-α mRNA in lysed cells as well as their surrounding media as compared to control cells, as well as increased transcript half life as measured over four hours post stimulation with transcription inhibitor actinomycin D. The increases in mRNA half-life elicited by mtDNA were comparable to those observed after LPS addition. Stimulation also caused increased binding of TNF-α mRNA to the RNA binding protein, AUF1, as measured by immunoprecipitation of RNA-protein complexes and assayed for TNF-α binding by PCR. These results demonstrate that mitochondrial damage-associated molecular patterns regulate TNF-α mRNA expression at the post-transcriptional level through AUF1, an mRNA destabilizing factor. This is a novel mechanism that likely contributes to sepsis pathophysiology, and demonstrates the involvement of the mitochondrial fission and fusion balance and its regulation in the sepsis innate immune response

Visualizing Collective Discursive User Interactions in Online Life Science Communities

This paper highlights the rationale for the development of BioViz, a tool to help visualize the existence of collective user interactions in online life science communities. The first community studied has approximately 22,750 unique users and the second has 35,000. Making sense of the number of interactions between actors in these networks in order to discern patterns of collective organization and intelligent behavior is challenging. One of the complications is that forums - our object of interest - can vary in their purpose and remit (e.g. the role of gender in the life sciences to forums of praxis such as one exploring the cell line culturing) and this shapes the structure of the forum organization itself. Our approach took a random sample of 53 forums which were manually analyzed by our research team and interactions between actors were recorded as arcs between nodes. The paper focuses on a discussion of the utility of our approach, but presents some brief results to highlight the forms of knowledge that can be gained in identifying collective group formations. Specifically, we found that by using a matrix-based visualization approach, we were able to see patterns of collective behavior which we believe is valuable both to the study of collective intelligence and the design of virtual organizations.Comment: Presented at Collective Intelligence conference, 2012 (arXiv:1204.2991

The Australian workplace barometer: report on psychosocial safety climate and worker health in Australia

The Australian Workplace Barometer project aims to provide science driven evidence of Australian work conditions and their relationships to workplace health and productivity, through a national monitoring and surveillance system. This report was commissioned by Safe Work Australia to provide a summary of the results from data obtained from six Australian states and territories: New South Wales, South Australia, Western Australia, Tasmania, the Australian Capital Territory and the Northern Territory. The data provides evidence relating to psychosocial risk factors in the working Australian population as well as an analysis of relationships between risk factors and employee health and motivational outcomes

The hydrological function of organo-mineral soil grasslands in UK uplands

Despite the common global occurrence of grasslands on organo-mineral soils, very little is known about their associated hydrology. The UK uplands, as source areas for flood waters, are of considerable interest as locations that could be managed to reduce downstream river discharge peaks, and these areas are frequently covered with organo-mineral soil grasslands. This thesis examines how the management of UK upland organo-mineral grasslands influences soil properties, the production and control of overland flow, and river flow peak response to large storm events. Fieldwork was conducted in Swindale, Cumbria, assessing six different grassland types. Soils were highly permeable with significant differences in properties as the result of natural heterogeneity. Shallow soil depth was considered to be the dominant control over soil water storage, where soils frequently became waterlogged, producing overland flow up to 60% of the time. Land management, and seasonal growth and decay of vegetation, significantly influenced surface roughness, strongly affecting overland flow velocity. Winter overland flow velocity was significantly higher than in summer, and significant changes also occurred following vegetation cutting or grazing density alterations. Using empirical data, SD-TOPMODEL was used to predict river discharge peak size and timing in response to major storm events for different seasons and management scenarios in Swindale, and Calderdale, Yorkshire. Seasonality altered river discharge peaks by -5.5% to +2.2% and conservation management reduced peaks by up to 42% compared to the same storms occurring on recent land use. Overall, soil hydrological function was associated most with physical catchment characteristics, whereas grassland vegetation, and its influence on overland flow, was strongly associated with season and management. Where physical characteristics cannot be changed, grassland management was recommended as an effective means of ‘slowing the flow’ for flood mitigation, accounting for their role within a mosaiced upland landscape, management practicalities, climate change and other ecosystem services

'Are We Not Human?' Stories of Stigma, Disability and HIV from Lusaka, Zambia and Their Implications for Access to Health Services.

BACKGROUND: The advent of anti-retroviral therapy (ART) in Southern Africa holds the promise of shifting the experience of HIV toward that of a manageable chronic condition. However, this potential can only be realized when persons living with HIV are able to access services without barriers, which can include stigma. Our qualitative study explored experiences of persons living with disabilities (PWD) in Lusaka, Zambia who became HIV-positive (PWD/HIV+). METHODS AND FINDINGS: We conducted interviews with 32 participants (21 PWD/HIV+ and 11 key informants working in the fields of HIV and/or disability). Inductive thematic analysis of interview transcripts was informed by narrative theory. Participants' accounts highlighted the central role of stigma experienced by PWD/HIV+, with stigmatizing attitudes closely linked to prevailing societal assumptions that PWD are asexual. Seeking diagnostic and treatment services for HIV was perceived as evidence of PWD being sexually active. Participants recounted that for PWD/HIV+, stigma was enacted in a variety of settings, including the queue for health services, their interactions with healthcare providers, and within their communities. Stigmatizing accounts told about PWD/HIV+ were described as having important consequences. Not only did participants recount stories of internalized stigma (with its damaging effects on self-perception), but also that negative experiences resulted in some PWD preferring to "die quietly at home" rather than being subjected to the stigmatizing gaze of others when attempting to access life-preserving ART. Participants recounted how experiences of stigma also affected their willingness to continue ART, their willingness to disclose their HIV status to others, as well as their social relations. However, participants also offered counter-stories, actively resisting stigmatizing accounts and portraying themselves as resilient and resourceful social actors. CONCLUSIONS: The study highlights a significant barrier to healthcare experienced by PWD/HIV+, with important implications for the future design and equitable delivery of HIV services in Zambia. Stigma importantly affects the abilities of PWD/HIV+ to manage their health conditions

High Resolution STIS/HST and HIRES/Keck Spectra of Three Weak MgII Absorbers Toward PG 1634+706

High resolution optical (HIRES/Keck) and UV (STIS/HST) spectra, covering a large range of chemical transitions, are analyzed for three single-cloud weak MgII absorption systems along the line of sight toward the quasar PG 1634+706. Weak MgII absorption lines in quasar spectra trace metal-enriched environments that are rarely closely associated with the most luminous galaxies (>0.05L^*). The two weak MgII systems at z=0.81 and z=0.90 are constrained to have >=solar metallicity, while the metallicity of the z=0.65 system is not as well-constrained, but is consistent with >1/10th solar. These weak MgII clouds are likely to be local pockets of high metallicity in a lower metallicity environment. All three systems have two phases of gas, a higher density region that produces narrower absorption lines for low ionization transitions, such as MgII, and a lower density region that produces broader absorption lines for high ionization transitions, such as CIV. The CIV profile for one system (at z=0.81) can be fit with a single broad component (b~10 km/s), but those for the other two systems require one or two additional offset high ionization clouds. Two possible physical pictures for the phase structure are discussed: one with a low-ionization, denser phase embedded in a lower density surrounding medium, and the other with the denser clumps surrounding more highly ionized gas.Comment: 32 pages, 4 figures; to appear in ApJ on May 20, 200

Followup Observations of SDSS and CRTS Candidate Cataclysmic Variables

We present photometry of 11 and spectroscopy of 35 potential cataclysmic variables from the Sloan Digital Sky Survey, the Catalina Real-Time Transient Survey and vsnet-alerts. The photometry results include quasi-periodic oscillations during the decline of V1363 Cyg, nightly accretion changes in the likely Polar (AM Herculis binary) SDSS J1344+20, eclipses in SDSS J2141+05 with an orbital period of 76+/-2 min, and possible eclipses in SDSS J2158+09 at an orbital period near 100 min. Time-resolved spectra reveal short orbital periods near 80 min for SDSS J0206+20, 85 min for SDSS J1502+33, and near 100 min for CSS J0015+26, RXS J0150+37, SDSS J1132+62, SDSS J2154+15 and SDSS J2158+09. The prominent HeII line and velocity amplitude of SDSS J2154+15 are consistent with a Polar nature for this object, while the lack of this line and a low velocity amplitude argue against this classification for RXS J0150+37. Single spectra of 10 objects were obtained near outburst and the rest near quiescence, confirming the dwarf novae nature of these objects.Comment: 34 pages, 14 figures, in press at A

Two approaches to longitudinal qualitative analyses in rehabilitation and disability research.

Purpose: Although relatively unknown within the field of rehabilitation, qualitative longitudinal research is ideal for rehabilitation and disability research that aims to understand health-related challenges over time. We describe the strengths and challenges of longitudinal qualitative research using two concrete examples.Materials and methods: Qualitative longitudinal research often involves in-depth interviews of participants on multiple occasions over time. Analytic approaches are complex, summarizing data both cross-sectionally and longitudinally. We present two detailed analytic approaches used in research with people living with HIV in Zambia and Canada.Results: Our experiences provide three recommendations. First, development of the initial analytic coding framework should include both inductive and deductive approaches. Second, given the large quantity of data generated through longitudinal qualitative research, it is important to proactively develop strategies for data analysis and management. Third, as retention of participants is challenging over time, we recommend the use of a consistent interviewer over the duration of the study to promote a trusting relationship.Conclusions: Longitudinal qualitative research has much to offer researchers and can provide clinicians with insights on the challenges of living with chronic and episodic disability. The flexibility in analytic approaches allows for diverse strategies to best address the rehabilitation and disability research questions and allow for insights into living with disability over time