We previously quantified frailty in aged mice with frailty index (FI) that used specialized equipment to measure health parameters. Here we developed a simplified, noninvasive method to quantify frailty through clinical assessment of C57BL/6J mice (5–28 months) and compared the relationship between FI scores and age in mice and humans. FIs calculated with the original performance-based eight-item FI increased from 0.06±0.01 at 5 months to 0.36±0.06 at 19 months and 0.38±0.04 at 28 months (n = 14). By contrast, the increase was graded with a 31-item clinical FI (0.02±0.005 at 5 months; 0.12±0.008 at 19 months; 0.33±0.02 at 28 months; n = 14). FI scores calculated from 70 self-report items from the first wave of the Survey of Health, Ageing and Retirement in Europe were plotted as function of age (n = 30,025 people). The exponential relationship between FI scores and age (normalized to 90% mortality) was similar in mice and humans for the clinical FI but not the eight-item FI. This noninvasive FI based on clinical measures can be used in longitudinal studies to quantify frailty in mice. Unlike the performance-based eight-item mouse FI, the clinical FI exhibits key features of the FI established for use in humans.
BackgroundThe changes that occur in the microbiome of aging individuals are unclear, especially in light of the imperfect correlation of frailty with age. Studies in older human subjects have reported subtle effects, but these results may be confounded by other variables that often change with age such as diet and place of residence. To test these associations in a more controlled model system, we examined the relationship between age, frailty, and the gut microbiome of female C57BL/6 J mice.ResultsThe frailty index, which is based on the evaluation of 31 clinical signs of deterioration in mice, showed a near-perfect correlation with age. We observed a statistically significant relationship between age and the taxonomic composition of the corresponding microbiome. Consistent with previous human studies, the Rikenellaceae family, which includes the Alistipes genus, was the most significantly overrepresented taxon within middle-aged and older mice.The functional profile of the mouse gut microbiome also varied with host age and frailty. Bacterial-encoded functions that were underrepresented in older mice included cobalamin (B12) and biotin (B7) biosynthesis, and bacterial SOS genes associated with DNA repair. Conversely, creatine degradation, associated with muscle wasting, was overrepresented within the gut microbiomes of the older mice, as were bacterial-encoded β-glucuronidases, which can influence drug-induced epithelial cell toxicity. Older mice also showed an overabundance of monosaccharide utilization genes relative to di-, oligo-, and polysaccharide utilization genes, which may have a substantial impact on gut homeostasis.ConclusionWe have identified taxonomic and functional patterns that correlate with age and frailty in the mouse microbiome. Differences in functions related to host nutrition and drug pharmacology vary in an age-dependent manner, suggesting that the availability and timing of essential functions may differ significantly with age and frailty. Future work with larger cohorts of mice will aim to separate the effects of age and frailty, and other factors.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-014-0050-9) contains supplementary material, which is available to authorized users.
The capacity to biomineralize is closely linked to the rapid expansion of animal life during the early Cambrian, with many skeletonized phyla first appearing in the fossil record at this time. The appearance of disparate molluscan forms during this period leaves open the possibility that shells evolved independently and in parallel in at least some groups. To test this proposition and gain insight into the evolution of structural genes that contribute to shell fabrication, we compared genes expressed in nacre (mother-of-pearl) forming cells in the mantle of the bivalve Pinctada maxima and the gastropod Haliotis asinina. Despite both species having highly lustrous nacre, we find extensive differences in these expressed gene sets. Following the removal of housekeeping genes, less than 10% of all gene clusters are shared between these molluscs, with some being conserved biomineralization genes that are also found in deuterostomes. These differences extend to secreted proteins that may localize to the organic shell matrix, with less than 15% of this secretome being shared. Despite these differences, H. asinina and P. maxima both secrete proteins with repetitive low-complexity domains (RLCDs). Pinctada maxima RLCD proteins-for example, the shematrins-are predominated by silk/fibroin-like domains, which are absent from the H. asinina data set. Comparisons of shematrin genes across three species of Pinctada indicate that this gene family has undergone extensive divergent evolution within pearl oysters. We also detect fundamental bivalve-gastropod differences in extracellular matrix proteins involved in mollusc-shell formation. Pinctada maxima expresses a chitin synthase at high levels and several chitin deacetylation genes, whereas only one protein involved in chitin interactions is present in the H. asinina data set, suggesting that the organic matrix on which calcification proceeds differs fundamentally between these species. Large-scale differences in genes expressed in nacre-forming cells of Pinctada and Haliotis are compatible with the hypothesis that gastropod and bivalve nacre is the result of convergent evolution. The expression of novel biomineralizing RLCD proteins in each of these two molluscs and, interestingly, sea urchins suggests that the evolution of such structural proteins has occurred independently multiple times in the Metazoa.
Many carnivore populations escaped extinction during the twentieth century as a result of legal protections, habitat restoration, and changes in public attitudes. However, encounters between carnivores, livestock, and humans are increasing in some areas, raising concerns about the costs of carnivore conservation. We present a method to predict sites of human-carnivore conflicts regionally, using as an example the mixed forest-agriculture landscapes of Wisconsin and Minnesota (U.S.A.). We used a matched-pair analysis of 17 landscape variables in a geographic information system to discriminate affected areas from unaffected areas at two spatial scales (townships and farms). Wolves (Canis lupus) selectively preyed on livestock in townships with high proportions of pasture and high densities of deer (Odocoileus virginianus) combined with low proportions of crop lands, coniferous forest, herbaceous wetlands, and open water. These variables plus road density and farm size also appeared to predict risk for individual farms when we considered Minnesota alone. In Wisconsin only, farm size, crop lands, and road density were associated with the risk of wolf attack on livestock. At the level of townships, we generated two state-wide maps to predict the extent and location of future predation on livestock. Our approach can be applied wherever spatial data are available on sites of conflict between wildlife and humans. Predicción de Conflicto Humano-Carnívoro: un Modelo Espacial Basado en 25 Años de Datos de Depredación de Ganado por Lobos Resumen: Muchas poblaciones de carnívoros lograron evitar la extinción durante el siglo veinte debido a protecciones legales, restauración de hábitat y cambios en las actitudes del público. Sin embargo, los encuentros entre carnívoros, ganado y humanos están incrementando en algunasáreas, lo cual es causa de preocupación en cuanto a los costos de la conservación de carnívoros. Presentamos un método para predecir los sitios de conflictos humanos -carnívoro a nivel regional, utilizando como ejemplo los paisajes mixtos de bosques-agricultura de Wisconsin y Minnesota (E. U. A.). Utilizamos un análisis apareado de 17 variables del paisaje en un sistema § §Current address: Living Landscapes Program, Wildlife Conservation Society, Treves et al. Predicting Human-Carnivore Conflict 115de información geográfica para discriminaráreas afectadas deáreas no afectadas a dos escalas espaciales (municipios y establecimientos). Los lobos (Canis lupus) depredaron selectivamente el ganado en municipios con proporciones altas de pasto y altas densidades de venado (Odocoileus virginianus) combinadas con proporciones bajas de terrenos agrícolas bosques de coníferas, humedales herbáceos y cuerpos de agua abiertos. Estas variables, junto con la densidad de caminos y el tamaño del establecimiento, permitieron además predecir el riesgo para establecimientos individuales cuando analizamos solamente el estado de Minnesota. En Wisconsin, solamente el tamaño del establecimiento, los terrenos agrícolas y la densidad de cam...
Although many common diseases occur mostly in old age, the impact of ageing itself on disease risk and expression often goes unevaluated. To consider the impact of ageing requires some useful means of measuring variability in health in animals of the same age. In humans, this variability has been quantified by counting age-related health deficits in a frailty index. Here we show the results of extending that approach to mice. Across the life course, many important features of deficit accumulation are present in both species. These include gradual rates of deficit accumulation (slope = 0.029 in humans; 0.036 in mice), a submaximal limit (0.54 in humans; 0.44 in mice), and a strong relationship to mortality (1.05 [1.04–1.05] in humans; 1.15 [1.12–1.18] in mice). Quantifying deficit accumulation in individual mice provides a powerful new tool that can facilitate translation of research on ageing, including in relation to disease.
In an effort to increase conservation effectiveness through the use of Earth observation technologies, a group of remote sensing scientists affiliated with government and academic institutions and conservation organizations identified 10 questions in conservation for which the potential to be answered would be greatly increased by use of remotely sensed data and analyses of those data. Our goals were to increase conservation practitioners' use of remote sensing to support their work, increase collaboration between the conservation science and remote sensing communities, identify and develop new and innovative uses of remote sensing for advancing conservation science, provide guidance to space agencies on how future satellite missions can support conservation science, and generate support from the public and private sector in the use of remote sensing data to address the 10 conservation questions. We identified a broad initial list of questions on the basis of an email chain-referral survey. We then used a workshop-based iterative and collaborative approach to whittle the list down to these final questions (which represent 10 major themes in conservation): How can global Earth observation data be used to model species distributions and abundances? How can remote sensing improve the understanding of animal movements? How can remotely sensed ecosystem variables be used to understand, monitor, and predict ecosystem response and resilience to multiple stressors? How can remote sensing be used to monitor the effects of climate on ecosystems? How can near real-time ecosystem monitoring catalyze threat reduction, governance and regulation compliance, and resource management decisions? How can remote sensing inform configuration of protected area networks at spatial extents relevant to populations of target species and ecosystem services? How can remote sensing-derived products be used to value and monitor changes in ecosystem services? How can remote sensing be used to monitor and evaluate the effectiveness of conservation efforts? How does the expansion and intensification of agriculture and aquaculture alter ecosystems and the services they provide? How can remote sensing be used to determine the degree to which ecosystems are being disturbed or degraded and the effects of these changes on species and ecosystem functions?
-type calcium currents in atrial and ventricular myocytes, as well as in pacemaker cells (sinoatrial node myocytes). In contrast, our studies of the electrophysiological effects of CNP on cardiac fibroblasts demonstrated an NPR-C-G i -phospholipase-C-dependent activation of a non-selective cation current mediated by transient receptor potential (TRP) channels.It is also known that CNP and BNP have important anti-proliferative effects in cardiac fibroblasts that appear to involve NPR-C. In the mammalian resistance vessels, including mesenteric and coronary arteries, CNP has been found to function as an NPR-C-dependent endothelium-derived hyperpolarizing factor that regulates local blood flow and systemic blood pressure by hyperpolarizing smooth muscle cells. In this review we highlight the role of NPR-C in mediating these NP effects in myocytes and fibroblasts from the heart as well as in vascular smooth muscle cells.
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