Understanding the bio-physical characteristics of a fen ecosystem to inform management and conserve the rare habitat

Fen-wetland ecosystems are rare nationwide. Their unique groundwater regime and chemistry, along with a floating, vegetated peat mat that may occur, support diverse and rare plant and wildlife communities. A fen’s ecological benefits are considered even greater within an urbanized setting through its natural attenuation of runoff and pollutants, though these ecosystem services may diminish should the urban-sourced impacts eventually alter the fen’s bio-physical condition. Here we will present how determining a fen’s key bio-physical factors and understanding their combined sensitivity to external processes is necessary to define and address potential threats to a fen’s conservation. Located within a 100-acre Metro-owned natural area along the lower Willamette River, the last known remaining fen composed of a groundwater-fed lake with a densely vegetated floating peat mat in the region is vulnerable to threats that could alter its fragile biochemistry. Threats include stormwater runoff, groundwater reductions from local pumping, nutrient input from septic tanks, and invasive species. To inform conservation measures, Metro’s goal was to assess the fen’s watershed inputs and bio-physical condition by studying the site hydrology, water and soil quality, and vegetation. Initial results reveal a unique ecosystem with counter groundwater and surface-water flow directions due to the unique geologic setting, eutrophic lake conditions from high nutrient loading and concentration, acidic water chemistry and soils from parent bedrock materials, and a diverse plant community consisting of 27 taxa of rare plants. Ongoing monitoring of the fen is helping to assess its condition, help detect future trends, and inform preservation of this unique habitat and potential recommendations for restoring disturbed fens elsewhere in the region

Lactate dehydrogenase expression modulates longevity and neurodegeneration in Drosophila melanogaster

Lactate dehydrogenase (LDH) catalyzes the conversion of glycolysis-derived pyruvate to lactate. Lactate has been shown to play key roles in brain energetics and memory formation. However, lactate levels are elevated in aging and Alzheimer\u27s disease patients, and it is not clear whether lactate plays protective or detrimental roles in these contexts. Here we show that Ldh transcript levels are elevated and cycle with diurnal rhythm in the heads of aged flies and this is associated with increased LDH protein, enzyme activity, and lactate concentrations. To understand the biological significance of increased Ldh gene expression, we genetically manipulated Ldh levels in adult neurons or glia. Overexpression of Ldh in both cell types caused a significant reduction in lifespan whereas Ldh down-regulation resulted in lifespan extension. Moreover, pan-neuronal overexpression of Ldh disrupted circadian locomotor activity rhythms and significantly increased brain neurodegeneration. In contrast, reduction of Ldh in neurons delayed age-dependent neurodegeneration. Thus, our unbiased genetic approach identified Ldh and lactate as potential modulators of aging and longevity in flies

HIV Protective Efficacy and Correlates of Tenofovir Blood Concentrations in a Clinical Trial of PrEP for HIV Prevention

Background: Antiretroviral pre-exposure prophylaxis (PrEP) is a novel HIV prevention strategy for which adherence is a known determinant of efficacy. Blood concentrations of PrEP medications are one objective marker of adherence. Methods: In a placebo-controlled PrEP efficacy trial of tenofovir disoproxil fumarate (TDF) and TDF with emtricitabine (FTC/TDF) among 4747 African women and men with an HIV-infected partner, we measured plasma tenofovir concentrations from participants in the active PrEP arms: 29 HIV seroconverters (cases) and 196 randomly selected controls who remained uninfected. Results: Among controls, 71% of visits had tenofovir concentrations >40 ng/mL, consistent with steady-state daily dosing, compared with 21% of cases at the visit HIV was first detected. Pill count data indicated that 96% of controls and 66% of cases had >80% adherence for these same visits. The estimated protective effect of PrEP against HIV, based on concentrations >40 ng/mL, was 88% (95% confidence interval: 60 to 96, P 40 ng/mL at month 1, 75% maintained this concentration at month 12. Only 5 of 29 seroconverters seemed to be consistently adherent to PrEP. Tenofovir concentrations >40 ng/mL were associated with older age and shorter time on study; concentrations ≤40 ng/mL occurred more commonly when participants reported no sex with their HIV-infected partner. Conclusions: Plasma concentrations of tenofovir consistent with daily dosing were highly predictive of protection from HIV acquisition. Most of those who took PrEP seemed to have high and consistent adherence

External sources of clean technology: evidence from the clean development mechanism

New technology is fundamental to sustainable development. However, inventors from industrialized countries often refuse technology transfer because they worry about reverse-engineering. When can clean technology transfer succeed? We develop a formal model of the political economy of North–South technology transfer. According to the model, technology transfer is possible if (1) the technology in focus has limited global commercial potential or (2) the host developing country does not have the capacity to absorb new technologies for commercial use. If both conditions fail, inventors from industrialized countries worry about the adverse competitiveness effects of reverse-engineering, so technology transfer fails. Data analysis of technology transfer in 4,894 projects implemented under the Kyoto Protocol’s Clean Development Mechanism during the 2004–2010 period provides evidence in support of the model

Astro2020 Science White Paper: Triggered High-Priority Observations of Dynamic Solar System Phenomena

Unexpected dynamic phenomena have surprised solar system observers in the past and have led to important discoveries about solar system workings. Observations at the initial stages of these events provide crucial information on the physical processes at work. We advocate for long-term/permanent programs on ground-based and space-based telescopes of all sizes - including Extremely Large Telescopes (ELTs) - to conduct observations of high-priority dynamic phenomena, based on a predefined set of triggering conditions. These programs will ensure that the best initial dataset of the triggering event are taken; separate additional observing programs will be required to study the temporal evolution of these phenomena. While not a comprehensive list, the following are notional examples of phenomena that are rare, that cannot be anticipated, and that provide high-impact advances to our understandings of planetary processes. Examples include: new cryovolcanic eruptions or plumes on ocean worlds; impacts on Jupiter, Saturn, Uranus, or Neptune; extreme eruptions on Io; convective superstorms on Saturn, Uranus, or Neptune; collisions within the asteroid belt or other small-body populations; discovery of an interstellar object passing through our solar system (e.g. 'Oumuamua); and responses of planetary atmospheres to major solar flares or coronal mass ejections.Comment: Astro2020 white pape

COMBO-FISH Enables High Precision Localization Microscopy as a Prerequisite for Nanostructure Analysis of Genome Loci

With the completeness of genome databases, it has become possible to develop a novel FISH (Fluorescence in Situ Hybridization) technique called COMBO-FISH (COMBinatorial Oligo FISH). In contrast to other FISH techniques, COMBO-FISH makes use of a bioinformatics approach for probe set design. By means of computer genome database searching, several oligonucleotide stretches of typical lengths of 15–30 nucleotides are selected in such a way that all uniquely colocalize at the given genome target. The probes applied here were Peptide Nucleic Acids (PNAs)—synthetic DNA analogues with a neutral backbone—which were synthesized under high purity conditions. For a probe repetitively highlighted in centromere 9, PNAs labeled with different dyes were tested, among which Alexa 488® showed reversible photobleaching (blinking between dark and bright state) a prerequisite for the application of SPDM (Spectral Precision Distance/Position Determination Microscopy) a novel technique of high resolution fluorescence localization microscopy. Although COMBO-FISH labeled cell nuclei under SPDM conditions sometimes revealed fluorescent background, the specific locus was clearly discriminated by the signal intensity and the resulting localization accuracy in the range of 10–20 nm for a detected oligonucleotide stretch. The results indicate that COMBO-FISH probes with blinking dyes are well suited for SPDM, which will open new perspectives on molecular nanostructural analysis of the genome

Biological effects of sodium phenylbutyrate and taurursodiol in Alzheimer's disease

INTRODUCTION: Sodium phenylbutyrate and taurursodiol (PB and TURSO) is hypothesized to mitigate endoplasmic reticulum stress and mitochondrial dysfunction, two of many mechanisms implicated in Alzheimer's disease (AD) pathophysiology. METHODS: The first‐in‐indication phase 2a PEGASUS trial was designed to gain insight into PB and TURSO effects on mechanistic targets of engagement and disease biology in AD. The primary clinical efficacy outcome was a global statistical test combining three endpoints relevant to disease trajectory (cognition [Mild/Moderate Alzheimer's Disease Composite Score], function [Functional Activities Questionnaire], and total hippocampal volume on magnetic resonance imaging). Secondary clinical outcomes included various cognitive, functional, and neuropsychiatric assessments. Cerebrospinal fluid (CSF) biomarkers spanning multiple pathophysiological pathways in AD were evaluated in participants with both baseline and Week 24 samples (exploratory outcome). RESULTS: PEGASUS enrolled 95 participants (intent‐to‐treat [ITT] cohort); cognitive assessments indicated significantly greater baseline cognitive impairment in the PB and TURSO (n = 51) versus placebo (n = 44) group. Clinical efficacy outcomes did not significantly differ between treatment groups in the ITT cohort. CSF interleukin‐15 increased from baseline to Week 24 within the placebo group (n = 34). In the PB and TURSO group (n = 33), reductions were observed in core AD biomarkers phosphorylated tau‐181 (p‐tau181) and total tau; synaptic and neuronal degeneration biomarkers neurogranin and fatty acid binding protein‐3 (FABP3); and gliosis biomarker chitinase 3‐like protein 1 (YKL‐40), while the oxidative stress marker 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG) increased. Between‐group differences were observed for the Aβ42/40 ratio, p‐tau181, total tau, neurogranin, FABP3, YKL‐40, interleukin‐15, and 8‐OHdG. Additional neurodegeneration, inflammation, and metabolic biomarkers showed no differences between groups. DISCUSSION: While between‐group differences in clinical outcomes were not observed, most likely due to the small sample size and relatively short treatment duration, exploratory biomarker analyses suggested that PB and TURSO engages multiple pathophysiologic pathways in AD. Highlights: Proteostasis and mitochondrial stress play key roles in Alzheimer's disease (AD). Sodium phenylbutyrate and taurursodiol (PB and TURSO) targets these mechanisms. The PEGASUS trial was designed to assess PB and TURSO effects on biologic AD targets. PB and TURSO reduced exploratory biomarkers of AD and neurodegeneration. Supports further clinical development of PB and TURSO in neurodegenerative diseases

Solar system Deep Time-Surveys of atmospheres, surfaces, and rings

Imaging and resolved spectroscopy reveal varying environmental conditions in our dynamic solar system. Many key advances have focused on how these conditions change over time. Observatory-level commitments to conduct annual observations of solar system bodies would establish a long-term legacy chronicling the evolution of dynamic planetary atmospheres, surfaces, and rings. Science investigations will use these temporal datasets to address potential biosignatures, circulation and evolution of atmospheres from the edge of the habitable zone to the ice giants, orbital dynamics and planetary seismology with ring systems, exchange between components in the planetary system, and the migration and processing of volatiles on icy bodies, including Ocean Worlds. The common factor among these diverse investigations is the need for a very long campaign duration, and temporal sampling at an annual cadence.Comment: 10 pages, 4 figures: submitted for Astro2020 White Pape

Different paths to the modern state in Europe: the interaction between domestic political economy and interstate competition

Theoretical work on state formation and capacity has focused mostly on early modern Europe and on the experience of western European states during this period. While a number of European states monopolized domestic tax collection and achieved gains in state capacity during the early modern era, for others revenues stagnated or even declined, and these variations motivated alternative hypotheses for determinants of fiscal and state capacity. In this study we test the basic hypotheses in the existing literature making use of the large date set we have compiled for all of the leading states across the continent. We find strong empirical support for two prevailing threads in the literature, arguing respectively that interstate wars and changes in economic structure towards an urbanized economy had positive fiscal impact. Regarding the main point of contention in the theoretical literature, whether it was representative or authoritarian political regimes that facilitated the gains in fiscal capacity, we do not find conclusive evidence that one performed better than the other. Instead, the empirical evidence we have gathered lends supports to the hypothesis that when under pressure of war, the fiscal performance of representative regimes was better in the more urbanized-commercial economies and the fiscal performance of authoritarian regimes was better in rural-agrarian economie