Preparing for Climatic Change: The Water, Salmon, and Forests of the Pacific Northwest

The impacts of year-to-year and decade-to-decade climatic variations on some of the Pacific Northwest’s key natural resources can be quantified to estimate sensitivity to regional climatic changes expected as part of anthropogenic global climatic change. Warmer, drier years, often associated with El Niño events and/or the warm phase of the Pacific Decadal Oscillation, tend to be associated with below-average snowpack, streamflow, and flood risk, below-average salmon survival, below-average forest growth, and above-average risk of forest fire. During the 20th century, the region experienced a warming of 0.8 ◦C. Using output from eight climate models, we project a further warming of 0.5–2.5 ◦C (central estimate 1.5 ◦C) by the 2020s, 1.5–3.2 ◦C (2.3◦C) by the 2040s, and an increase in precipitation except in summer. The foremost impact of a warming climate will be the reduction of regional snowpack, which presently supplies water for ecosystems and human uses during the dry summers. Our understanding of past climate also illustrates the responses of human management systems to climatic stresses, and suggests that a warming of the rate projected would pose significant challenges to the management of natural resources. Resource managers and planners currently have few plans for adapting to or mitigating the ecological and economic effects of climatic change

Preparing for Climatic Change: The Water, Salmon, and Forests of the Pacific Northwest

The impacts of year-to-year and decade-to-decade climatic variations on some of the Pacific Northwest’s key natural resources can be quantified to estimate sensitivity to regional climatic changes expected as part of anthropogenic global climatic change. Warmer, drier years, often associated with El Niño events and/or the warm phase of the Pacific Decadal Oscillation, tend to be associated with below-average snowpack, streamflow, and flood risk, below-average salmon survival, below-average forest growth, and above-average risk of forest fire. During the 20th century, the region experienced a warming of 0.8 ◦C. Using output from eight climate models, we project a further warming of 0.5–2.5 ◦C (central estimate 1.5 ◦C) by the 2020s, 1.5–3.2 ◦C (2.3◦C) by the 2040s, and an increase in precipitation except in summer. The foremost impact of a warming climate will be the reduction of regional snowpack, which presently supplies water for ecosystems and human uses during the dry summers. Our understanding of past climate also illustrates the responses of human management systems to climatic stresses, and suggests that a warming of the rate projected would pose significant challenges to the management of natural resources. Resource managers and planners currently have few plans for adapting to or mitigating the ecological and economic effects of climatic change

Compartmentalized PDE4A5 signaling impairs hippocampal synaptic plasticity and long-term memory

Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo. Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling

Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies

Ebola virus (EBOV) is an enveloped, single-stranded RNA virus that can cause Ebola virus disease (EVD). It is thought that EVD survivors are protected against subsequent infection with EBOV and that neutralising antibodies to the viral surface glycoprotein (GP) are potential correlates of protection. Serological studies are vital to assess neutralising antibodies targeted to EBOV GP; however, handling of EBOV is limited to containment level 4 laboratories. Pseudotyped viruses can be used as alternatives to live viruses, which require high levels of bio-containment, in serological and viral entry assays. However, neutralisation capacity can differ among pseudotyped virus platforms. We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The sensitivity, specificity and correlation with live EBOV neutralisation were greater for the VSV-based pseudotyped virus system, which is particularly important when evaluating EBOV vaccine responses and immuno-therapeutics. Therefore, the EBOV GP pseudotyped VSV neutralisation assay reported here could be used to provide a better understanding of the putative correlates of protection against EBOV

Constitutive TRIM22 expression in the respiratory airway confers a pre-existing defence against influenza A virus infection

The induction of antiviral effector proteins as part of a homeostatically controlled innate immune response to infection plays a critical role in limiting the propagation and transmission of respiratory pathogens. However, the prolonged induction of this immune response can lead to lung hyperinflammation, tissue damage, and respiratory failure. We hypothesized that tissues exposed to the constant threat of infection may constitutively express higher levels of antiviral effector proteins to reduce the need to activate potentially harmful innate immune defences. By analysing transcriptomic data derived from a range of human tissues, we identify lung tissue to express constitutively higher levels of antiviral effector genes relative to that of other mucosal and non-mucosal tissues. By using primary cell lines and the airways of rhesus macaques, we show the interferon-stimulated antiviral effector protein TRIM22 (TRIpartite Motif 22) to be constitutively expressed in the lung independently of viral infection or innate immune stimulation. These findings contrast with previous reports that have shown TRIM22 expression in laboratory-adapted cell lines to require interferon stimulation. We demonstrate that constitutive levels of TRIM22 are sufficient to inhibit the onset of human and avian influenza A virus (IAV) infection by restricting the onset of viral transcription independently of interferon-mediated innate immune defences. Thus, we identify TRIM22 to confer a pre-existing (intrinsic) intracellular defence against IAV infection in cells derived from the respiratory tract. Our data highlight the importance of tissue-specific and cell-type dependent patterns of pre-existing immune gene expression in the intracellular restriction of IAV from the outset of infection

Detectors for the James Webb Space Telescope Near-Infrared Spectrograph I: Readout Mode, Noise Model, and Calibration Considerations

We describe how the James Webb Space Telescope (JWST) Near-Infrared Spectrograph's (NIRSpec's) detectors will be read out, and present a model of how noise scales with the number of multiple non-destructive reads sampling-up-the-ramp. We believe that this noise model, which is validated using real and simulated test data, is applicable to most astronomical near-infrared instruments. We describe some non-ideal behaviors that have been observed in engineering grade NIRSpec detectors, and demonstrate that they are unlikely to affect NIRSpec sensitivity, operations, or calibration. These include a HAWAII-2RG reset anomaly and random telegraph noise (RTN). Using real test data, we show that the reset anomaly is: (1) very nearly noiseless and (2) can be easily calibrated out. Likewise, we show that large-amplitude RTN affects only a small and fixed population of pixels. It can therefore be tracked using standard pixel operability maps.Comment: 55 pages, 10 figure

Discovery and Rossiter-McLaughlin Effect of Exoplanet Kepler-8b

We report the discovery and the Rossiter-McLaughlin effect of Kepler-8b, a transiting planet identified by the NASA Kepler Mission. Kepler photometry and Keck-HIRES radial velocities yield the radius and mass of the planet around this F8IV subgiant host star. The planet has a radius RP = 1.419 RJ and a mass, MP = 0.60 MJ, yielding a density of 0.26 g cm^-3, among the lowest density planets known. The orbital period is P = 3.523 days and orbital semima jor axis is 0.0483+0.0006/-0.0012 AU. The star has a large rotational v sin i of 10.5 +/- 0.7 km s^-1 and is relatively faint (V = 13.89 mag), both properties deleterious to precise Doppler measurements. The velocities are indeed noisy, with scatter of 30 m s^-1, but exhibit a period and phase consistent with the planet implied by the photometry. We securely detect the Rossiter-McLaughlin effect, confirming the planet's existence and establishing its orbit as prograde. We measure an inclination between the projected planetary orbital axis and the projected stellar rotation axis of lambda = -26.9 +/- 4.6 deg, indicating a moderate inclination of the planetary orbit. Rossiter-McLaughlin measurements of a large sample of transiting planets from Kepler will provide a statistically robust measure of the true distribution of spin-orbit orientations for hot jupiters in general.Comment: 26 pages, 8 figures, 2 tables; In preparation for submission to the Astrophysical Journa

Organizational factors and depression management in community-based primary care settings

Abstract Background Evidence-based quality improvement models for depression have not been fully implemented in routine primary care settings. To date, few studies have examined the organizational factors associated with depression management in real-world primary care practice. To successfully implement quality improvement models for depression, there must be a better understanding of the relevant organizational structure and processes of the primary care setting. The objective of this study is to describe these organizational features of routine primary care practice, and the organization of depression care, using survey questions derived from an evidence-based framework. Methods We used this framework to implement a survey of 27 practices comprised of 49 unique offices within a large primary care practice network in western Pennsylvania. Survey questions addressed practice structure (e.g., human resources, leadership, information technology (IT) infrastructure, and external incentives) and process features (e.g., staff performance, degree of integrated depression care, and IT performance). Results The results of our survey demonstrated substantial variation across the practice network of organizational factors pertinent to implementation of evidence-based depression management. Notably, quality improvement capability and IT infrastructure were widespread, but specific application to depression care differed between practices, as did coordination and communication tasks surrounding depression treatment. Conclusions The primary care practices in the network that we surveyed are at differing stages in their organization and implementation of evidence-based depression management. Practical surveys such as this may serve to better direct implementation of these quality improvement strategies for depression by improving understanding of the organizational barriers and facilitators that exist within both practices and practice networks. In addition, survey information can inform efforts of individual primary care practices in customizing intervention strategies to improve depression management.http://deepblue.lib.umich.edu/bitstream/2027.42/78269/1/1748-5908-4-84.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/2/1748-5908-4-84-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78269/3/1748-5908-4-84.pdfPeer Reviewe