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

Sociodemographic factors and patient perceptions are associated with attitudes to kidney transplantation among haemodialysis patients

Background. Treatment decisions made by patients with chronic kidney disease are crucial in the renal transplantation process. These decisions are influenced, amongst other factors, by attitudes towards different treatment options, which are modulated by knowledge and perceptions about the disease and its treatment and many other subjective factors. Here we study the attitude of dialysis patients to renal transplantation and the association of sociodemographic characteristics, patient perceptions and experiences with this attitude. Methods. In a cross-sectional study, all patients from eight dialysis units in Budapest, Hungary, who were on haemodialysis for at least 3 months were approached to complete a self-administered questionnaire. Data collected from 459 patients younger than 70 years were analysed in this manuscript. Results. Mean age of the study population was 53 +/- 12 years, 54% were male and the prevalence of diabetes was 22%. Patients with positive attitude to renal transplantation were younger (51 +/- 11 versus 58 +/- 11 years), better educated, more likely to be employed (11% versus 4%) and had prior transplantation (15% versus 7%)(P < 0.05 for all). In a multivariate model, negative patient perceptions about transplantation, negative expectations about health outcomes after transplantation and the presence of fears about the transplant surgery were associated, in addition to incre- asing age, with unwillingness to consider transplantation. Conclusions. Negative attitudes to renal transplantation are associated with potentially modifiable factors. Based on this we suggest that it would be necessary to develop standardized, comprehensible patient information systems and personalized decision support to facilitate modality selection and to enable patients to make fully informed treatment decisions

Paläoökologie und Geochemie quartärer Seesedimente auf Baffin Island, Kanadische Arktis

Amarok, Tulugak und Ukalik sind kleine, ultra-oligotrophe Seen auf Baffin Island, kanadische Arktis, die im Frühholozän eine natürliche Schwermetallanreicherung aufweisen, welche mit der von rezenten, belasteten Sedimenten vergleichbar ist. Während der letzten Eiszeit waren diese Seen nicht von Gletschermassen bedeckt (Refugien), so dass die Seen und ihre Einzugsgebiete während der letzten 40 000 Jahre aktive Ökosysteme waren. Die paläoökologischen Bedingungen wechselten zwischen kalten Zeiten mit geringer Vegetationsbedeckung, geringer Bodenbildung, starker Erosion, allochthonen klastischen Sedimenten, geringer Produktivität und sauren pH-Werten und wärmeren Zeiten mit Zunahme von Vegetationsbedeckung und Bodenbildung, geringerer Erosion, autochthonen organischen Sedimenten, stärkerer Produktivität und höheren pH-Werten. Die Veränderungen des Paläo-pH werden vor allem durch hydrologische und biogeochemische Prozesse in den Seen selbst gesteuert, weniger durch die Basenbereitstellung aus den Einzugsgebieten. Eine effektive synsedimentäre Konzentration von Schwermetallen im organischen Anteil hat im Frühholozän dazu geführt, dass unter bestimmten hydrologischen und ökologischen Bedingungen natürlicherweise Konzentrationen von Schwermetallen auftreten, die z. T. weit über dem normalerweise anzutreffenden geogenen Hintergrund liegen.researc

ColabFit Exchange: open-access datasets for data-driven interatomic potentials

Data-driven (DD) interatomic potentials (IPs) trained on large collections of first principles calculations are rapidly becoming essential tools in the fields of computational materials science and chemistry for performing atomic-scale simulations. Despite this, apart from a few notable exceptions, there is a distinct lack of well-organized, public datasets in common formats available for use with IP development. This deficiency precludes the research community from implementing widespread benchmarking, which is essential for gaining insight into model performance and transferability, while also limiting the development of more general, or even universal, IPs. To address this issue, we introduce the ColabFit Exchange, the first database providing open access to a large collection of systematically organized datasets from multiple domains that is especially designed for IP development. The ColabFit Exchange is publicly available at \url{https://colabfit.org/}, providing a web-based interface for exploring, downloading, and contributing datasets. Composed of data collected from the literature or provided by community researchers, the ColabFit Exchange consists of 106 datasets spanning nearly 70,000 unique chemistries, and is intended to continuously grow. In addition to outlining the software framework used for constructing and accessing the ColabFit Exchange, we also provide analyses of data, quantifying the diversity and proposing metrics for assessing the relative quality and atomic environment coverage of different datasets. Finally, we demonstrate an end-to-end IP development pipeline, utilizing datasets from the ColabFit Exchange, fitting tools from the KLIFF software package, and validation tests provided by the OpenKIM framework

A direct association between amber and dinosaur remains provides paleoecological insights

This work is licensed under a Creative Commons Attribution 4.0 International License.Hadrosaurian dinosaurs were abundant in the Late Cretaceous of North America, but their habitats remain poorly understood. Cretaceous amber is also relatively abundant, yet it is seldom found in direct stratigraphic association with dinosaur remains. Here we describe an unusually large amber specimen attached to a Prosaurolophus jaw, which reveals details of the contemporaneous paleoforest and entomofauna. Fourier-transform Infrared spectroscopy and stable isotope composition (H and C) suggest the amber formed from resins exuded by cupressaceous conifers occupying a coastal plain. An aphid within the amber belongs to Cretamyzidae, a Cretaceous family suggested to bark-feed on conifers. Distinct tooth row impressions on the amber match the hadrosaur’s alveolar bone ridges, providing some insight into the taphonomic processes that brought these remains together

Variations in the fundamental constants in the QSO host J1148+5251 at z = 6.4 and the BR1202−0725 system at z = 4.7

We use sensitive observations of three high-redshift sources: [C ii] ^(2)P_(3/2) → ^(2)P_(1/2) fine-structure and CO (J = 2 → 1) rotational transitions for the z = 6.4 quasar (QSO) host galaxy J1148+5251 taken with the Plateau de Bure Interferometer (PdBI) and Jansky Very Large Array, respectively, and [C ii] and CO (J = 5 → 4) transitions from the QSO BR1202−0725 and its companion sub-millimetre galaxy (SMG) at z = 4.7 taken with the Atacama Large Millimeter Array and the PdBI. We use these observations to place constraints on the quantity Δz=zCO−zCii for each source where zCO and zCii are the observed redshifts of the CO rotational transition and [C ii] fine-structure transition, respectively, using a combination of approaches: (1) modelling the emission line profiles using ‘shapelets’ – a complete orthonormal set of basis functions that allow us to recreate most physical line shapes – to compare both the emission redshifts and the line profiles themselves, in order to make inferences about the intrinsic velocity differences between the molecular and atomic gas, and (2) performing a marginalization over all model parameters in order to calculate a non-parametric estimate of Δz. We derive 99 per cent confidence intervals for the marginalized posterior of Δz of (−1.9 ± 1.3) × 10^(−3), (−3 ± 8) × 10^(−4) and (−2 ± 4) × 10^(−3) for J1148+5251, and the BR1202−0725 QSO and SMG, respectively. We show that the [C ii] and CO (J = 2 → 1) line profiles for J1148+5251 are consistent with each other within the limits of the data, whilst the [C ii] and CO (J = 5 → 4) line profiles from the BR1202−0725 QSO and SMG, respectively, have 65 and >99.9 per cent probabilities of being inconsistent, with the CO (J = 5 → 4) lines ∼30 per cent wider than the [C ii] lines. Therefore, whilst the observed values of Δz can correspond to variations in the quantity ΔF/F with cosmic time, where F = α^2/μ, with α the fine-structure constant and μ the proton-to-electron mass ratio, of both (−3.3 ± 2.3) × 10^(−4) for a look-back time of 12.9 Gyr and of (−5 ± 15) × 10^(−5) for a look-back time of 12.4 Gyr, we propose that they are the result of the two species of gas being spatially separated as indicated by the inconsistencies in their line profiles

A novel approach to understanding bird communities using informed diversity estimates at local and regional scales in northern California and southern Oregon

Assessment and preservation of biodiversity has been a central theme of conservation biology since the discipline\u27s inception. However, when diversity estimates are based purely on measures of presence–absence, or even abundance, they do not directly assess in what way focal habitats support the life history needs of individual species making up biological communities. Here, we move beyond naïve measures of occurrence and introduce the concept of “informed diversity” indices which scale estimates of avian species richness and community assemblage by two critical phases of their life cycle: breeding and molt. We tested the validity of the “informed diversity” concept using bird capture data from multiple locations in northern California and southern Oregon to examine patterns of species richness among breeding, molting, and naïve (based solely on occurrence) bird communities at the landscape and local scales using linear regression, community similarity indices, and a Detrended Correspondence Analysis (DCA). At the landscape scale, we found a striking pattern of increased species richness for breeding, molting, and naïve bird communities further inland and at higher elevations throughout the study area. At the local scale, we found that some sites with species‐rich naïve communities were in fact species‐poor when informed by breeding status, indicating that naïve richness may mask more biologically meaningful patterns of diversity. We suggest that land managers use informed diversity estimates instead of naïve measures of diversity to identify ecologically valuable wildlife habitat

Distinct Clinical and Pathological Features Are Associated with the BRAFT1799A(V600E) Mutation in Primary Melanoma

The BRAFT1799A mutation encodes BRAFV600E that leads to activation of the mitogen-activated protein kinase pathway. This study aimed to assess the clinico-pathological features of primary invasive melanomas containing the BRAFT1799A mutation. Patients (n=251) with invasive primary melanomas from Australia were interviewed and examined with respect to their melanoma characteristics and risk factors. Independent review of pathology, allele-specific PCR for the BRAFT1799A mutation, immunohistochemical staining with Ki67, and phospho-histone-H3 (PH3) were performed. The BRAFT1799A mutation was found in 112 (45%) of the primary melanomas. Associations with the BRAFT1799A mutation (P<0.05) were as follows: low tumor thickness (odds ratio (OR)=3.3); low mitotic rate (OR=2.0); low Ki67 score (OR=5.0); low PH3 score (OR=3.3); superficial spreading melanoma (OR=10.0); pigmented melanoma (OR=3.7); a lack of history of solar keratoses (OR=2.7); a location on the trunk (OR=3.4) or extremity (OR=2.0); a high level of self-reported childhood sun exposure (OR=2.0); ≤50 years of age (OR=2.5); and fewer freckles (OR=2.5). We conclude that the BRAFT1799A mutation has associations with host phenotype, tumor location, and pigmentation. Although implicated in the control of the cell cycle, the BRAFT1799A mutation is associated with a lower rate of tumor proliferation

High-Redshift Metals. II. Probing Reionization Galaxies with Low-Ionization Absorption Lines at Redshift Six

We present a survey for low-ionization metal absorption line systems towards 17 QSOs at redshifts z_em=5.8-6.4. Nine of our objects were observed at high resolution with either Keck/HIRES or Magellan/MIKE, and the remainder at moderate resolution with Keck/ESI. The survey spans 5.3 < z_abs < 6.4 and has a pathlength interval \Delta X=39.5, or \Delta z=8.0. In total we detect ten systems, five of which are new discoveries. The line-of-sight number density is consistent with the combined number density at z~3 of DLAs and sub-DLAs, which comprise the main population of low-ionization systems at lower redshifts. This apparent lack of evolution may occur because low ionization systems are hosted by lower-mass halos at higher redshifts, or because the mean cross section of low-ionization gas at a given halo mass increases with redshift due to the higher densities and lower ionizing background. The roughly constant number density notably contrasts with the sharp decline at z > 5.3 in the number density of highly-ionized systems traced by C IV. The low-ionization systems at z~6 span a similar range of velocity widths as lower-redshift sub-DLAs but have significantly weaker lines at a given width. This implies that the mass-metallicity relation of the host galaxies evolves towards lower metallicities at higher redshifts. These systems lack strong Si IV and C IV, which are common among lower-redshift DLAs and sub-DLAs. This is consistent, however, with a similar decrease in the metallicity of the low- and high-ionization phases, and does not necessarily indicate a lack of nearby, highly-ionized gas. The high number density of low-ionization systems at z~6 suggests that we may be detecting galaxies below the current limits of i-dropout and Ly-alpha emission galaxy surveys. These systems may therefore be the first direct probes of the `typical' galaxies responsible for hydrogen reionization.Comment: 15 pages, 15 figures, submitted to Ap

Melting Alpine Glaciers Enrich High-Elevation Lakes with Reactive Nitrogen

Alpine glaciers have receded substantially over the last century in many regions of the world. Resulting changes in glacial runoff not only affect the hydrological cycle, but can also alter the physical (i.e., turbidity from glacial flour) and biogeochemical properties of downstream ecosystems. Here we compare nutrient concentrations, transparency gradients, algal biomass, and fossil diatom species richness in two sets of high-elevation lakes: those fed by snowpack melt alone (SF lakes) and those fed by both glacial and snowpack meltwaters (GSF lakes). We found that nitrate (NO3-) concentrations in the GSF lakes were 1-2 orders of magnitude higher than in SF lakes. Although nitrogen (N) limitation is common in alpine lakes, algal biomass was lower in highly N-enriched GSF lakes than in the N-poor SF lakes. Contrary to expectations, GSF lakes were more transparent than SF lakes to ultraviolet and equally transparent to photosynthetically active radiation.Sediment diatom assemblages had lower taxonomic richness in the GSF lakes, a feature that has persisted over the last century. Our results demonstrate that the presence of glaciers on alpine watersheds more strongly influences NO3- concentrations in high-elevation lake ecosystems than any other geomorphic or biogeographic characteristic