KECK HIRES Spectroscopy of APM 08279+5255

With an optical R-band magnitude of 15.2, the recently discovered z=3.911 BAL quasar APM 08279+5255 is an exceptionally bright high redshift source. Its brightness has allowed us to acquire a high signal-to-noise ratio (~100), high resolution (~6 km/s) spectrum using the HIRES echelle spectrograph on the 10-m Keck I telescope. Given the quality of the data, these observations provide an unprecedented view of associated and intervening absorption systems. Here we announce the availability of this spectrum to the general astronomical community and present a brief analysis of some of its main features.Comment: 21 pages including 5 figures. Accepted for publication by PAS

The immune environment of the mammary gland fluctuates during post-lactational regression and correlates with tumour growth rate

Post-lactational mammary gland regression encompasses extensive programmed cell death and removal of milk-producing epithelial cells, breakdown of extracellular matrix components and redifferentiation of stromal adipocytes. This highly regulated involution process is associated with a transient increased risk of breast cancer in women. Using a syngeneic tumour model, we show that tumour growth is significantly altered depending on the stage of involution at which tumour cells are implanted. Tumour cells injected at day 3 involution grew faster than those in nulliparous mice, whereas tumours initiated at day 6 involution grew significantly slower. These differences in tumour progression correlate with distinct changes in innate immune cells, in particular among F4/80-expressing macrophages and among TCRδ(+) unconventional T cells. Breast cancer post-pregnancy risk is exacerbated in older first-time mothers and, in our model, initial tumour growth is moderately faster in aged mice compared with young mice. Our results have implications for breast cancer risk and the use of anti-inflammatory therapeutics for postpartum breast cancers

Differences in signal contrast and camouflage among different colour variations of a stomatopod crustacean, Neogonodactylus oerstedii

Animal colouration is often a trade-off between background matching for camouflage from predators, and conspicuousness for communication with con- or heterospecifics. Stomatopods are marine crustaceans known to use colour signals during courtship and contests, while their overall body colouration may provide camouflage. However, we have little understanding of how stomatopods perceive these signals in their environment or whether overall body coloration does provide camouflage from predators. Neogonodactylus oerstedii assess meral spot colour during contests, and meral spot colour varies depending on local habitat. By calculating quantum catch for N. oerstedii’s 12 photoreceptors associated with chromatic vision, we found that variation in meral spot total reflectance does not function to increase signal contrast in the local habitat. Neogonodactylus oerstedii also show between-habitat variation in dorsal body colouration. We used visual models to predict a trichromatic fish predator’s perception of these colour variations. Our results suggest that sandy and green stomatopods are camouflaged from a typical fish predator in rubble fields and seagrass beds, respectively. To our knowledge, this is the first study to investigate signal contrast and camouflage in a stomatopod. These results provide new insight into the function and evolution of colouration in a species with a complex visual system

Extracellular Vesicles Secreted in Response to Cytokine Exposure Increase Mitochondrial Oxygen Consumption in Recipient Cells

Extracellular vesicles (EVs) are small, membrane-bound nanoparticles released from most, if not all cells, and can carry functionally active cargo (proteins, nucleic acids) which can be taken up by neighboring cells and mediate physiologically relevant effects. In this capacity, EVs are being regarded as novel cell-to-cell communicators, which may play important roles in the progression of neurodegenerative diseases, like Alzheimer’s disease (AD). Aside from the canonical physical hallmarks of this disease [amyloid β (Aβ) plaques, neurofibrillary tangles, and widespread cell death], AD is characterized by chronic neuroinflammation and mitochondrial dysfunction. In the current study, we sought to better understand the role of tumor necrosis factor-alpha (TNF-α), known to be involved in inflammation, in mediating alterations in mitochondrial function and EV secretion. Using an immortalized hippocampal cell line, we observed significant reductions in several parameters of mitochondrial oxygen consumption after a 24-h exposure period to TNF-α. In addition, after TNF-α exposure we also observed significant upregulation of two microRNAs (miRNAs; miR-34a and miR-146a) associated with mitochondrial dysfunction in secreted EVs. Despite this, when naïve cells are exposed to EVs isolated from TNF-α treated cells, mitochondrial respiration, proton leak, and reactive oxygen species (ROS) production are all significantly increased. Collectively these data indicate that a potent proinflammatory cytokine, TNF-α, induces significant mitochondrial dysfunction in a neuronal cell type, in part via the secretion of EVs, which significantly alter mitochondrial activity in recipient cells

Intentional research design in implementation science: implications for the use of nomothetic and idiographic assessment

The advancement of implementation science is dependent on identifying assessment strategies that can address implementation and clinical outcome variables in ways that are valid, relevant to stakeholders, and scalable. This paper presents a measurement agenda for implementation science that integrates the previously disparate assessment traditions of idiographic and nomothetic approaches. Although idiographic and nomothetic approaches are both used in implementation science, a review of the literature on this topic suggests that their selection can be indiscriminate, driven by convenience, and not explicitly tied to research study design. As a result, they are not typically combined deliberately or effectively. Thoughtful integration may simultaneously enhance both the rigor and relevance of assessments across multiple levels within health service systems. Background on nomothetic and idiographic assessment is provided as well as their potential to support research in implementation science. Drawing from an existing framework, seven structures (of various sequencing and weighting options) and five functions (Convergence, Complementarity, Expansion, Development, Sampling) for integrating conceptually distinct research methods are articulated as they apply to the deliberate, design-driven integration of nomothetic and idiographic assessment approaches. Specific examples and practical guidance are provided to inform research consistent with this framework. Selection and integration of idiographic and nomothetic assessments for implementation science research designs can be improved. The current paper argues for the deliberate application of a clear framework to improve the rigor and relevance of contemporary assessment strategies

Mitochondrial Impairment in Cerebrovascular Endothelial Cells is Involved in the Correlation between Body Temperature and Stroke Severity

Stroke is the second leading cause of death worldwide. The prognostic influence of body temperature on acute stroke in patients has been recently reported; however, hypothermia has confounded experimental results in animal stroke models. This work aimed to investigate how body temperature could prognose stroke severity as well as reveal a possible mitochondrial mechanism in the association of body temperature and stroke severity. Lipopolysaccharide (LPS) compromises mitochondrial oxidative phosphorylation in cerebrovascular endothelial cells (CVECs) and worsens murine experimental stroke. In this study, we report that LPS (0.1 mg/kg) exacerbates stroke infarction and neurological deficits, in the mean time LPS causes temporary hypothermia in the hyperacute stage during 6 hours post-stroke. Lower body temperature is associated with worse infarction and higher neurological deficit score in the LPS-stroke study. However, warming of the LPS-stroke mice compromises animal survival. Furthermore, a high dose of LPS (2 mg/kg) worsens neurological deficits, but causes persistent severe hypothermia that conceals the LPS exacerbation of stroke infarction. Mitochondrial respiratory chain complex I inhibitor, rotenone, replicates the data profile of the LPS-stroke study. Moreover, we have confirmed that rotenone compromises mitochondrial oxidative phosphorylation in CVECs. Lastly, the pooled data analyses of a large sample size (n=353) demonstrate that stroke mice have lower body temperature compared to sham mice within 6 hours post-surgery; the body temperature is significantly correlated with stroke outcomes; linear regression shows that lower body temperature is significantly associated with higher neurological scores and larger infarct volume. We conclude that post-stroke body temperature predicts stroke severity and mitochondrial impairment in CVECs plays a pivotal role in this hypothermic response. These novel findings suggest that body temperature is prognostic for stroke severity in experimental stroke animal models and may have translational significance for clinical stroke patients - targeting endothelial mitochondria may be a clinically useful approach for stroke therapy