The role of PPARα in gene regulation in mouse liver is well characterized. However, less is known about the role of PPARα in human liver. The aim of the present study was to better characterize the ...impact of PPARα activation on gene regulation in human liver. To that end, chimeric mice containing hepatocyte humanized livers were given an oral dose of 300 mg/kg fenofibrate daily for 4 days. Livers were collected and analyzed by hematoxilin and eosin staining, qPCR, and transcriptomics. Transcriptomics data were compared with existing datasets on PPARα activation in normal mouse liver, human primary hepatocytes, and human precision cut liver slices.
Of the different human liver models, the gene expression profile of hepatocyte humanized livers most closely resembled actual human liver. In the hepatocyte humanized mouse livers, the human hepatocytes exhibited excessive lipid accumulation. Fenofibrate increased the size of the mouse but not human hepatocytes, and tended to reduce steatosis in the human hepatocytes. Quantitative PCR indicated that induction of PPARα targets by fenofibrate was less pronounced in the human hepatocytes than in the residual mouse hepatocytes. Transcriptomics analysis indicated that, after filtering, a total of 282 genes was significantly different between fenofibrate- and control-treated mice (P < 0.01). 123 genes were significantly lower and 159 genes significantly higher in the fenofibrate-treated mice, including many established PPARα targets such as FABP1, HADHB, HADHA, VNN1, PLIN2, ACADVL and HMGCS2. According to gene set enrichment analysis, fenofibrate upregulated interferon/cytokine signaling-related pathways in hepatocyte humanized liver, but downregulated these pathways in normal mouse liver. Also, fenofibrate downregulated pathways related to DNA synthesis in hepatocyte humanized liver but not in normal mouse liver.
The results support the major role of PPARα in regulating hepatic lipid metabolism, and underscore the more modest effect of PPARα activation on gene regulation in human liver compared to mouse liver. The data suggest that PPARα may have a suppressive effect on DNA synthesis in human liver, and a stimulatory effect on interferon/cytokine signalling.
Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the ...effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene- and gender-specific guidelines has been acknowledged.
The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) developed a multidisciplinary working group consisting of surgeons, clinical and molecular geneticists, pathologists, epidemiologists, gastroenterologists, and patient representation to conduct a graded evidence review. The previous Mallorca guideline format was used to revise the clinical guidance. Consensus for the guidance statements was acquired by three Delphi voting rounds.
Recommendations for clinical and molecular identification of Lynch syndrome, surgical and endoscopic management of Lynch syndrome-associated colorectal cancer, and preventive measures for cancer were produced. The emphasis was on surgical and gastroenterological aspects of the cancer spectrum. Manchester consensus guidelines for gynaecological management were endorsed. Executive and layperson summaries were provided.
The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented.
We report the discovery of TOI 837b and its validation as a transiting planet. We characterize the system using data from the NASA Transiting Exoplanet Survey Satellite mission, the ESA Gaia mission, ...ground-based photometry from El Sauce and ASTEP400, and spectroscopy from CHIRON, FEROS, and Veloce. We find that TOI 837 is a T = 9.9 mag G0/F9 dwarf in the southern open cluster IC 2602. The star and planet are therefore million years old. Combining the transit photometry with a prior on the stellar parameters derived from the cluster color-magnitude diagram, we find that the planet has an orbital period of and is slightly smaller than Jupiter ( ). From radial velocity monitoring, we limit to less than 1.20 MJup (3 ). The transits either graze or nearly graze the stellar limb. Grazing transits are a cause for concern, as they are often indicative of astrophysical false-positive scenarios. Our follow-up data show that such scenarios are unlikely. Our combined multicolor photometry, high-resolution imaging, and radial velocities rule out hierarchical eclipsing binary scenarios. Background eclipsing binary scenarios, though limited by speckle imaging, remain a 0.2% possibility. TOI 837b is therefore a validated adolescent exoplanet. The planetary nature of the system can be confirmed or refuted through observations of the stellar obliquity and the planetary mass. Such observations may also improve our understanding of how the physical and orbital properties of exoplanets change in time.
We present a 3D map of extinction in the northern Galactic plane derived using photometry from the INT/WFC Photometric Hα Survey of the northern Galactic plane. The map has fine angular ( ∼ 10 ...arcmin) and distance (100 pc) sampling allied to a significant depth (≳5 kpc). We construct the map using a method based on a hierarchical Bayesian model described in a previous article by Sale. In addition to mean extinction, we also measure differential extinction, which arises from the fractal nature of the interstellar medium, and show that it will be the dominant source of uncertainty in estimates of extinction to some arbitrary position. The method applied also furnishes us with photometric estimates of the distance, extinction, effective temperature, surface gravity, and mass for ∼38 million stars. Both the extinction map and the catalogue of stellar parameters are made publicly available via http://www.iphas.org/extinction.
A long-standing enigma in plasma transport has been resolved by modeling of cold-pulse experiments conducted on the Alcator C-Mod tokamak. Controlled edge cooling of fusion plasmas triggers core ...electron heating on time scales faster than an energy confinement time, which has long been interpreted as strong evidence of nonlocal transport. This Letter shows that the steady-state profiles, the cold-pulse rise time, and disappearance at higher density as measured in these experiments are successfully captured by a recent local quasilinear turbulent transport model, demonstrating that the existence of nonlocal transport phenomena is not necessary for explaining the behavior and time scales of cold-pulse experiments in tokamak plasmas.
The Transiting Exoplanet Survey Satellite (TESS) recently observed 18 transits of the hot Jupiter WASP-4b. The sequence of transits occurred 81.6 11.7 s earlier than had been predicted, based on data ...stretching back to 2007. This is unlikely to be the result of a clock error, because TESS observations of other hot Jupiters (WASP-6b, 18b, and 46b) are compatible with a constant period, ruling out an 81.6 s offset at the 6.4 level. The 1.3 day orbital period of WASP-4b appears to be decreasing at a rate of ms per year. The apparent period change might be caused by tidal orbital decay or apsidal precession, although both interpretations have shortcomings. The gravitational influence of a third body is another possibility, though at present there is minimal evidence for such a body. Further observations are needed to confirm and understand the timing variation.
We present a new framework to study the time evolution and dynamics of the outer Van Allen belt electron fluxes. The framework is entirely based on the large‐scale solar wind storm drivers and their ...substructures. The Van Allen Probe observations, revealing the electron flux behavior throughout the outer belt, are combined with continuous, long‐term (over 1.5 solar cycles) geosynchronous orbit data set from GOES and solar wind measurements A superposed epoch analysis, where we normalize the timescales for each substructure (sheath, ejecta, and interface region) allows us to avoid smearing effects and to distinguish the electron flux evolution during various driver structures. We show that the radiation belt response is not random: The electron flux variations are determined by the combined effect of the structured solar wind driver and prestorm electron flux levels. In particular, we find that loss mechanisms dominate during stream interface regions, coronal mass ejection (CME) ejecta, and sheaths while enhancements occur during fast streams trailing the stream interface or the CME.
Key Points
We superpose the different substructures of each solar wind storm driver
During stream interface regions, CME ejecta and sheaths loss mechanisms dominate
Enhancements occur during fast streams trailing the stream interface or the CME
The Surface Water and Ocean Topography (SWOT) satellite mission planned for launch in 2020 will map river elevations and inundated area globally for rivers >100 m wide. In advance of this launch, we ...here evaluated the possibility of estimating discharge in ungauged rivers using synthetic, daily “remote sensing” measurements derived from hydraulic models corrupted with minimal observational errors. Five discharge algorithms were evaluated, as well as the median of the five, for 19 rivers spanning a range of hydraulic and geomorphic conditions. Reliance upon a priori information, and thus applicability to truly ungauged reaches, varied among algorithms: one algorithm employed only global limits on velocity and depth, while the other algorithms relied on globally available prior estimates of discharge. We found at least one algorithm able to estimate instantaneous discharge to within 35% relative root‐mean‐squared error (RRMSE) on 14/16 nonbraided rivers despite out‐of‐bank flows, multichannel planforms, and backwater effects. Moreover, we found RRMSE was often dominated by bias; the median standard deviation of relative residuals across the 16 nonbraided rivers was only 12.5%. SWOT discharge algorithm progress is therefore encouraging, yet future efforts should consider incorporating ancillary data or multialgorithm synergy to improve results.
Key Points:
SWOT discharge algorithms were tested on synthetic observations for 19 rivers
Algorithms accurately characterized temporal dynamics of river discharge
At least one algorithm estimated discharge to <35% relative RMSE on 14/16 of nonbraided rivers
Community-based participatory research (CBPR) answers the call for more patient-centered, community-driven research approaches to address growing health disparities. CBPR is a collaborative research ...approach that equitably involves community members, researchers, and other stakeholders in the research process and recognizes the unique strengths that each bring. The aim of CBPR is to combine knowledge and action to create positive and lasting social change. With its origins in psychology, sociology, and critical pedagogy, CBPR has become a common research approach in the fields of public health, medicine, and nursing. Although it is well aligned with psychology's ethical principles and research aims, it has not been widely implemented in psychology research. The present article introduces CBPR to a general psychology audience while considering the unique aims of and challenges in conducting psychology research. In this article, we define CBPR principles, differentiate it from a more traditional psychology research approach, retrace its historical roots, provide concrete steps for its implementation, discuss its potential benefits, and explore practical and ethical challenges for its integration into psychology research. Finally, we provide a case study of CBPR in psychology to illustrate its key constructs and implementation. In sum, CBPR is a relevant, important, and promising research framework that may guide the implementation of more effective, culturally appropriate, socially just, and sustainable community-based psychology research.
DS Tuc Ab is a Neptune-sized planet that orbits around a G star in the 45 Myr old Tucana-Horologium moving group. Here, we report the measurement of the sky-projected angle between the stellar spin ...axis and the planet's orbital axis, based on the observation of the Rossiter-McLaughlin effect during three separate planetary transits. The orbit appears to be well aligned with the equator of the host star, with a projected obliquity of . In addition to the distortions in the stellar absorption lines due to the transiting planet, we observed variations that we attribute to large starspots, with angular sizes of tens of degrees. The technique that we have developed for simultaneous modeling of starspots and the planet-induced distortions may be useful in other observations of planets around active stars.
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