Cre/lox generation of a novel whole-body Kiss1r KO mouse line recapitulates a hypogonadal, obese, and metabolically-impaired phenotype.

Kisspeptin and its receptor, Kiss1r, act centrally to stimulate reproduction. Recent evidence indicates that kisspeptin is also important for body weight and metabolism, as whole-body Kiss1r KO mice, developed with gene trap technology, display obesity and reduced metabolism. Kiss1r is expressed in brain and multiple peripheral tissues, but it is unknown which is responsible for the metabolic phenotype. Here, we sought to confirm that 1) the metabolic phenotype of the gene trap Kiss1r KOs is due to disruption of kisspeptin signaling and not off-target effects of viral mutagenesis, and 2) the Kiss1r flox line is suitable for creating conditional KOs to study the metabolic phenotype. We used Cre/lox technology (Zp3-Cre/Kiss1r flox) to develop a new global Kiss1r KO ("Kiss1r gKO") to compare with the original gene trap KO phenotype. We confirmed that deleting exon 2 of Kiss1r from the entire body induces hypogonadism in both sexes. Moreover, global deletion of Kiss1r induced obesity in females, but not males, along with increased adiposity and impaired glucose tolerance, similar to the gene trap Kiss1r KOs. Likewise, Kiss1r gKO females had decreased VO2 and VCO2, likely underlying their obesity. These findings support that our previous results in gene trap Kiss1r KOs are due to disrupted kisspeptin signaling, and further highlight a role for Kiss1r signaling in energy expenditure and metabolism besides controlling reproduction. Moreover, given Kiss1r expression in multiple cell-types, our findings indicate that the Kiss1r flox line is viable for future investigations to isolate specific target cells of kisspeptin's metabolic effects

Temporal and spatial variations in maximum river discharge from a new Russian data set

Floods cause more damage in Russia than any other natural disaster, and future climate model projections suggest that the frequency and magnitude of extreme hydrological events will increase in Russia with climate change. Here we analyze daily discharge records from a new data set of 139 Russian gauges in the Eurasian Arctic drainage basin with watershed areas from 16.1 to 50,000 km2 for signs of change in maximum river discharge. Several hypotheses about changes in maximum daily discharge and their linking with trends in precipitation over the cold season were tested. For the magnitude of maximum daily discharge we found relatively equal numbers of significant positive and negative trends across the Russian Arctic drainage basin, which draws into question the hypothesis of an increasing risk of extreme floods. We observed a significant shift to earlier spring discharge, which is consistent with documented changes in snowmelt and freeze‐thaw dates. Spatial analysis of changes in maximum discharge and cold season precipitation revealed consistency across most of the domain, the exception being the Lena basin. Trends in maximum discharge of the small‐ to medium‐sized rivers were generally consistent with aggregated signals found for the downstream gauges of the six largest Russian rivers. Although we observe regional changes in maximum discharge across the Russian Arctic drainage basin, no evidence of widespread trends in extreme discharge can be assumed from our analysis

The role of the North Atlantic Oscillation in controlling U.K. butterfly population size and phenology

Copyright @ 2012 The Authors. This article can be accessed from the links below.This article has been made available through the Brunel Open Access Publishing Fund.1. The North Atlantic Oscillation (NAO) exerts considerable control on U.K. weather. This study investigates the impact of the NAO on butterfly abundance and phenology using 34 years of data from the U.K. Butterfly Monitoring Scheme (UKBMS). 2. The study uses a multi-species indicator to show that the NAO does not affect overall U.K. butterfly population size. However, the abundance of bivoltine butterfly species, which have longer flight seasons, were found to be more likely to respond positively to the NAO compared with univoltine species, which show little or a negative response. 3. A positive winter NAO index is associated with warmer weather and earlier flight dates for Anthocharis cardamines (Lepidoptera: Pieridae), Melanargia galathea (Lepidoptera: Nymphalidae), Aphantopus hyperantus (Lepidoptera: Nymphalidae), Pyronia tithonus (Lepidoptera: Nymphalidae), Lasiommata megera (Lepidoptera: Nymphalidae) and Polyommatus icarus (Lepidoptera: Lycaenidae). In bivoltine species, the NAO affects the phenology of the first generation, the timing of which indirectly controls the timing of the second generation. 4. The NAO influences the timing of U.K. butterfly flight seasons more strongly than it influences population size.This study was supported by a multi-agency consortium led by the U.K. Department for Environment, Food and Rural Affairs (Defra), including the Countryside Council for Wales, the Joint Nature Conservation Committee, the Forestry Commission, Natural England, the Natural Environment Research Council, the Northern Ireland Environment Agency and Scottish Natural Heritage. This article is made available through the Brunel Open Access Publishing Fund

String-Inspired Chern-Simons Modified Gravity In 4-Dimensions

Chern-Simons modified gravity models in 4-dimensions are shown to be special cases of low energy effective string models to first order in the string constant.Comment: To appear in the European Physics Journal

Biased efficacy estimates in phase-III dengue vaccine trials due to heterogeneous exposure and differential detectability of primary infections across trial arms.

Vaccine efficacy (VE) estimates are crucial for assessing the suitability of dengue vaccine candidates for public health implementation, but efficacy trials are subject to a known bias to estimate VE toward the null if heterogeneous exposure is not accounted for in the analysis of trial data. In light of many well-characterized sources of heterogeneity in dengue virus (DENV) transmission, our goal was to estimate the potential magnitude of this bias in VE estimates for a hypothetical dengue vaccine. To ensure that we realistically modeled heterogeneous exposure, we simulated city-wide DENV transmission and vaccine trial protocols using an agent-based model calibrated with entomological and epidemiological data from long-term field studies in Iquitos, Peru. By simulating a vaccine with a true VE of 0.8 in 1,000 replicate trials each designed to attain 90% power, we found that conventional methods underestimated VE by as much as 21% due to heterogeneous exposure. Accounting for the number of exposures in the vaccine and placebo arms eliminated this bias completely, and the more realistic option of including a frailty term to model exposure as a random effect reduced this bias partially. We also discovered a distinct bias in VE estimates away from the null due to lower detectability of primary DENV infections among seronegative individuals in the vaccinated group. This difference in detectability resulted from our assumption that primary infections in vaccinees who are seronegative at baseline resemble secondary infections, which experience a shorter window of detectable viremia due to a quicker immune response. This resulted in an artefactual finding that VE estimates for the seronegative group were approximately 1% greater than for the seropositive group. Simulation models of vaccine trials that account for these factors can be used to anticipate the extent of bias in field trials and to aid in their interpretation

Are Participants Good Evaluators?

Managers of workforce training programs are often unable to afford costly, full-fledged experimental or nonexperimental evaluations to determine their programs’ impacts. Therefore, many rely on the survey responses of program participants to gauge program impacts. Smith, Whalley, and Wilcox present the first attempt to assess such measures despite their already widespread use in program evaluations. They develop a multidisciplinary framework for addressing the issue and apply it to three case studies: the National Job Training Partnership Act Study, the U.S. National Supported Work Demonstration, and the Connecticut Jobs First Program. Each of these studies were subjected to experimental evaluations that included a survey-based participant evaluation measure. The authors apply econometric methods specifically developed to obtain estimates of program impacts among individuals in the studies and then compare these estimates with survey-based participant evaluation measures to obtain an assessment of the surveys’ efficacy. The authors also discuss how their findings fit into the broader literatures in economics, psychology, and survey research.https://research.upjohn.org/up_press/1285/thumbnail.jp

Leptogenesis from Pseudo-Scalar Driven Inflation

We examine recent claims for a considerable amount of leptogenesis, in some inflationary scenarios, through the gravitational anomaly in the lepton number current. We find that when the short distances contributions are properly included the amount of lepton number generated is actually much smaller.Comment: JHEP style, 11 pages. Corrected typ

Prevalence of Hesperevax sparsiflora var. brevifolia (short-leaved evax) at Ocean Ranch, Humboldt County, California: exploring the effects of disturbance

The prevalence of special-status plants within a landscape can be an indicator of the ecological health of that site, and therefore inform restoration efforts and post-restoration monitoring. Hesperevax sparsiflora var. brevifolia (short-leaved evax) is a special status species found within the Ocean Ranch unit of Humboldt, California. A primary threat to native plant communities are invasive plant species. Coastal dune ecosystems are largely dominated by invasive species, including Ammophila arenaria (European beachgrass). To work towards the eradication of A. arenaria, the California Department of Fish and Wildlife utilized treatment combinations of herbicide and prescribed fire at Ocean Ranch in the fall of 2022. We worked with the California Department of Fish and Wildlife (CDFW) to study the density and abundance of H. sparsiflora var. brevifolia, proximity to A. arenaria, soil compaction, and distance to the road within specified areas. We estimated a total of 14,354,293 H. sparsiflora var. brevifolia individuals in the polygons we measured. We found that the further from A. arenaria, the greater the likelihood of H. sparsiflora var. brevifolia individuals. However, our findings showed that the number of individuals and distance to the road was not a significant relationship, and the relationship between the number of individuals in burned versus unburned quadrats was not significant. This project can serve to monitor the establishment of special-status species to observe the success of recent restorative treatments and to guide future restoration

KSwAGS: A Swift X-ray and UV Survey of the Kepler Field. I

We introduce the first phase of the Kepler-Swift Active Galaxies and Stars survey (KSwAGS), a simultaneous X-ray and UV survey of ~6 square degrees of the Kepler field using the Swift XRT and UVOT. We detect 93 unique X-ray sources with S/N>3 with the XRT, of which 60 have observed UV counterparts. We use the Kepler Input Catalog (KIC) to obtain the optical counterparts of these sources, and construct the X-ray to optical flux ratio as a first approximation of the classification of the source. The survey produces a mixture of stellar sources, extragalactic sources, and sources which we are not able to classify with certainty. We have obtained optical spectra for thirty of these targets, and are conducting an ongoing observing campaign to fully identify the sample. For sources classified as stellar or AGN with certainty, we construct SEDs using the 2MASS, UBV and GALEX data supplied for their optical counterparts by the KIC, and show that the SEDs differ qualitatively between the source types, and so can offer a method of classification in absence of a spectrum. Future papers in this series will analyze the timing properties of the stars and AGN in our sample separately. Our survey provides the first X-ray and UV data for a number of known variable stellar sources, as well as a large number of new X-ray detections in this well-studied portion of the sky. The KSwAGS survey is currently ongoing in the K2 ecliptic plane fields.Comment: Accepted for publication in the Astronomical Journal. 19 pages, 8 figures, 3 table