Genetic Diversity and Competitive Abilities of Dalea Purpurea (Fabaceae) from Remnant and Restored Grasslands

Allozyme and randomly amplified polymorphic DNA (RAPD) analyses were used to characterize the genetic relationships of Dalea purpurea from remnant and restored Illinois tallgrass prairies and a large remnant tallgrass prairie in Kansas. The remnant Illinois populations were less genetically diverse than the restored Illinois populations and the Kansas population. These restored Illinois populations were established with at least two seed sources that were locally collected. There was little population divergence (Fst = 0.042), which ST is consistent with other perennial forbs, while the genetic relationships among populations reflected geographic proximity. In a greenhouse competition experiment, differences in performance between seedlings was not related to the remnant or restored status of Illinois populations, but plants from Kansas were significantly smaller than Illinois plants. Genetic diversity and competitive ability were not associated with the size of the original source population. Our data indicate that using multiple local seed sources for restoration projects will maintain the local gene pool while enhancing the regional genetic diversity of this species

In vivo and in vitro assessment of mirtazapine pharmacokinetics in cats with liver disease.

BackgroundLiver disease (LD) prolongs mirtazapine half-life in humans, but it is unknown if this occurs in cats with LD and healthy cats.Hypothesis/objectivesTo determine pharmacokinetics of administered orally mirtazapine in vivo and in vitro (liver microsomes) in cats with LD and healthy cats.AnimalsEleven LD and 11 age-matched control cats.MethodsCase-control study. Serum was obtained 1 and 4 hours (22 cats) and 24 hours (14 cats) after oral administration of 1.88 mg mirtazapine. Mirtazapine concentrations were measured by liquid chromatography with tandem mass spectrometry. Drug exposure and half-life were predicted using limited sampling modeling and estimated using noncompartmental methods. in vitro mirtazapine pharmacokinetics were assessed using liver microsomes from 3 LD cats and 4 cats without LD.ResultsThere was a significant difference in time to maximum serum concentration between LD cats and control cats (median [range]: 4 [1-4] hours versus 1 [1-4] hours; P = .03). The calculated half-life of LD cats was significantly prolonged compared to controls (median [range]: 13.8 [7.9-61.4] hours versus 7.4 [6.7-9.1] hours; P < .002). Mirtazapine half-life was correlated with ALT (P = .002; r = .76), ALP (P < .0001; r = .89), and total bilirubin (P = .0008; r = .81). The rate of loss of mirtazapine was significantly different between microsomes of LD cats (-0.0022 min-1 , CI: -0.0050 to 0.00054 min-1 ) and cats without LD (0.01849 min-1 , CI: -0.025 to -0.012 min-1 ; P = .002).Conclusions and clinical importanceCats with LD might require less frequent administration of mirtazapine than normal cats

Bayesian joint inversion of controlled source electromagnetic and magnetotelluric data to image freshwater aquifer offshore New Jersey

Author Posting. © The Authors, 2019. This article is posted here by permission of The Royal Astronomical Society for personal use, not for redistribution. The definitive version was published in Geophysical Journal International 218(3), (2019): 1822-1837, doi: 10.1093/gji/ggz253.Joint inversion of multiple electromagnetic data sets, such as controlled source electromagnetic and magnetotelluric data, has the potential to significantly reduce uncertainty in the inverted electrical resistivity when the two data sets contain complementary information about the subsurface. However, evaluating quantitatively the model uncertainty reduction is made difficult by the fact that conventional inversion methods—using gradients and model regularization—typically produce just one model, with no associated estimate of model parameter uncertainty. Bayesian inverse methods can provide quantitative estimates of inverted model parameter uncertainty by generating an ensemble of models, sampled proportional to data fit. The resulting posterior distribution represents a combination of a priori assumptions about the model parameters and information contained in field data. Bayesian inversion is therefore able to quantify the impact of jointly inverting multiple data sets by using the statistical information contained in the posterior distribution. We illustrate, for synthetic data generated from a simple 1-D model, the shape of parameter space compatible with controlled source electromagnetic and magnetotelluric data, separately and jointly. We also demonstrate that when data sets contain complementary information about the model, the region of parameter space compatible with the joint data set is less than or equal to the intersection of the regions compatible with the individual data sets. We adapt a trans-dimensional Markov chain Monte Carlo algorithm for jointly inverting multiple electromagnetic data sets for 1-D earth models and apply it to surface-towed controlled source electromagnetic and magnetotelluric data collected offshore New Jersey, USA, to evaluate the extent of a low salinity aquifer within the continental shelf. Our inversion results identify a region of high resistivity of varying depth and thickness in the upper 500 m of the continental shelf, corroborating results from a previous study that used regularized, gradient-based inversion methods. We evaluate the joint model parameter uncertainty in comparison to the uncertainty obtained from the individual data sets and demonstrate quantitatively that joint inversion offers reduced uncertainty. In addition, we show how the Bayesian model ensemble can subsequently be used to derive uncertainty estimates of pore water salinity within the low salinity aquifer.We gratefully acknowledge funding support from National Science Foundation grants 1458392 and 1459035. We thank the captain and crew of the R.V. Marcus G. Langseth for a successful cruise and the Marine EM Lab at Scripps Institution of Oceanography for providing the instrumentation. We also thank Chris Armerding, Marah Dahn, John Desanto, Jimmy Elsenbeck, Matt Folsom, Keiichi Ishizu, Jeff Pepin, Charlotte Wiman and Georgie Zelenak for participating in the cruise. We gratefully acknowledge Alberto Malinverno for the idea to use a Monte Carlo scheme to estimate the distribution of pore fluid salinity, and William Menke for many constructive conversations and suggestions

The origin and evolution of the zodiacal dust cloud

We have now analyzed a substantial fraction of the IRAS observations of the zodiacal cloud, particularly in the 25 micron waveband. We have developed a gravitational perturbation theory that incorporates the effects of Poynting-Robertson light drag (Gomes and Dermott, 1992). We have also developed a numerical model, the SIMUL mode, that reproduces the exact viewing geometry of the IRAS telescope and calculates the distribution of thermal flux produced by any particular distribution of dust particle orbits (Dermott and Nicholson, 1989). With these tools, and using a distribution of orbits based on those of asteroidal particles with 3.4 micron radii whose orbits decay due to Poynting-Robertson light drag and are perturbed by the planets, we have been able to: (1) account for the inclination and node of the background zodiacal cloud observed by IRAS in the 25 micron waveband; (2) relate the distribution of orbits in the Hirayama asteroid families to the observed shapes of the IRAS solar system dustbands; and (3) show that there is observational evidence in the IRAS data for the transport of asteroidal particles from the main belt to the Earth by Poynting-Robertson light drag

Reverberation Mapping of the Kepler-Field AGN KA1858+4850

KA1858+4850 is a narrow-line Seyfert 1 galaxy at redshift 0.078 and is among the brightest active galaxies monitored by the Kepler mission. We have carried out a reverberation mapping campaign designed to measure the broad-line region size and estimate the mass of the black hole in this galaxy. We obtained 74 epochs of spectroscopic data using the Kast Spectrograph at the Lick 3-m telescope from February to November of 2012, and obtained complementary V-band images from five other ground-based telescopes. We measured the H-beta light curve lag with respect to the V-band continuum light curve using both cross-correlation techniques (CCF) and continuum light curve variability modeling with the JAVELIN method, and found rest-frame lags of lag_CCF = 13.53 (+2.03, -2.32) days and lag_JAVELIN = 13.15 (+1.08, -1.00) days. The H-beta root-mean-square line profile has a width of sigma_line = 770 +/- 49 km/s. Combining these two results and assuming a virial scale factor of f = 5.13, we obtained a virial estimate of M_BH = 8.06 (+1.59, -1.72) x 10^6 M_sun for the mass of the central black hole and an Eddington ratio of L/L_Edd ~ 0.2. We also obtained consistent but slightly shorter emission-line lags with respect to the Kepler light curve. Thanks to the Kepler mission, the light curve of KA1858+4850 has among the highest cadences and signal-to-noise ratios ever measured for an active galactic nucleus; thus, our black hole mass measurement will serve as a reference point for relations between black hole mass and continuum variability characteristics in active galactic nuclei

Autophagy Inhibition Delays Early but Not Late-Stage Metastatic Disease s

ABSTRACT The autophagy pathway has been recognized as a mechanism of survival and therapy resistance in cancer, yet the extent of autophagy's function in metastatic progression is still unclear. Therefore, we used murine models of metastatic cancer to investigate the effect of autophagy modulation on metastasis development. Pharmacologic and genetic autophagy inhibition were able to impede cell proliferation in culture, but did not impact the development of experimentally induced 4T1 and B16-F10 metastases. Similarly, autophagy inhibition by adjuvant chloroquine (CQ) treatment did not delay metastasis in an orthotopic 4T1, tumor-resection model. However, neoadjuvant CQ treatment or genetic autophagy inhibition resulted in delayed metastasis development, whereas stimulation of autophagy by trehalose hastened development. Cisplatin was also administered either as a single agent or in combination with CQ. The combination of cisplatin and CQ was antagonistic. The effects of autophagy modulation on metastasis did not appear to be due to alterations in the intrinsic metastatic capability of the cells, as modulating autophagy had no impact on migration, invasion, or anchorage-independent growth in vitro. To explore the possibility of autophagy's influence on the metastatic microenvironment, bone marrow-derived cells (BMDCs), which mediate the establishment of the premetastatic niche, were measured in the lung and in circulation. Trehalose-treated mice had significantly more BMDCs than either vehicle-or CQ-treated mice. Autophagy inhibition may be most useful as a treatment to impede early metastatic development. However, modulating autophagy may also alter the efficacy of platinum-based therapies, requiring caution when considering combination therapies

Kinetic Assessment and Therapeutic Modulation of Metabolic and Inflammatory Profiles in Mice on a High-Fat and Cholesterol Diet

The kinetics of metabolic and inflammatory parameters associated with obesity were evaluated in a murine diet-induced obesity (DIO) model using a diet high in fat and cholesterol. Cellular infiltration and mediator production were assessed and shown to be therapeutically modulated by the PPARgamma agonist rosiglitazone. C57BL/6 mice were maintained on a 45% fat/ 0.12% cholesterol (HF/CH) or Chow diet for 3, 6, 16, or 27 weeks. Flow cytometry was employed to monitor peripheral blood monocytes and adipose tissue macrophages (ATM). Gene expression and protein analysis methods were used to evaluate mediator production from total epididymal fat (EF), stromal vascular fraction (SVF), and sorted SVF cells. To investigate therapeutic intervention, mice were fed a HF/CH diet for 12 weeks and then a diet formulated with rosiglitazone (5 mg/kg) for an additional 6 weeks. A HF/CH diet correlated with obesity and a dramatic proinflammatory state. Therapeutic intervention with rosiglitazone attenuated the HF/CH induced inflammation. In addition, a novel population was found that expressed the highest levels of the pro-inflammatory mediators CCL2 and IL-6

Damaging variants in FOXI3 cause microtia and craniofacial microsomia

Q1Q1Pacientes con Microtia y Microsomía craneofacialPurpose: Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown. Methods: We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro. Results: We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3. Conclusion: Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort.https://orcid.org/0000-0003-3822-7780https://orcid.org/0000-0002-0729-6866Revista Internacional - IndexadaA1N

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page