Pathogenesis of feline enteric coronavirus infection.

Fifty-one specific pathogen-free (SPF) cats 10 weeks to 13 years of age were infected with a cat-to-cat fecal-oral passed strain of feline enteric coronavirus (FECV). Clinical signs ranged from unapparent to a mild and self-limiting diarrhea. Twenty-nine of these cats were FECV naïve before infection and followed sequentially for fecal virus shedding and antibody responses over a period of 8-48 months. Fecal shedding, as determined by real-time polymerase chain reaction (RT-PCR) from rectal swabs, appeared within a week and was significantly higher in kittens than older cats. FECV shedding remained at high levels for 2-10 months before eventually evolving into one of three excretion patterns. Eleven cats shed the virus persistently at varying levels over an observation period of 9-24 months. Eleven cats appeared to have periods of virus shedding interlaced with periods of non-shedding (intermittent or recurrent shedders), and seven cats ceased shedding after 5-19 months (average 12 months). There was no change in the patterns of virus shedding among cats that were excreting FECV at the time of a secondary challenge exposure. Four cats, which had ceased shedding, re-manifested a primary type infection when secondarily infected. Cats with higher feline coronavirus (FCoV) antibody titers were significantly more likely to shed virus, while cats with lower titers were significantly less likely to be shedding. Twenty-two kittens born to experimentally infected project queens began shedding virus spontaneously, but never before 9-10 weeks of age. Natural kittenhood infections appeared to be low grade and abortive. However, a characteristic primary type infection occurred following experimental infection with FECV at 12-15 weeks of age. Pregnancy, parturition and lactation had no influence on fecal shedding by queens. Methylprednisolone acetate treatment did not induce non-shedders to shed and shedders to increase shedding

Algebraic structure of stochastic expansions and efficient simulation

We investigate the algebraic structure underlying the stochastic Taylor solution expansion for stochastic differential systems.Our motivation is to construct efficient integrators. These are approximations that generate strong numerical integration schemes that are more accurate than the corresponding stochastic Taylor approximation, independent of the governing vector fields and to all orders. The sinhlog integrator introduced by Malham & Wiese (2009) is one example. Herein we: show that the natural context to study stochastic integrators and their properties is the convolution shuffle algebra of endomorphisms; establish a new whole class of efficient integrators; and then prove that, within this class, the sinhlog integrator generates the optimal efficient stochastic integrator at all orders.Comment: 19 page

Kinetics and Inhibition Studies of the L205R Mutant of cAMP-Dependent Protein Kinase Involved in Cushing’s Syndrome

Overproduction of cortisol by the hypothalamus–pituitary–adrenal hormone system results in the clinical disorder known as Cushing\u27s syndrome. Genomics studies have identified a key mutation (L205R) in the α‐isoform of the catalytic subunit of cAMP‐dependent protein kinase (PKACα) in adrenal adenomas of patients with adrenocorticotropic hormone‐independent Cushing\u27s syndrome. Here, we conducted kinetics and inhibition studies on the L205R‐PKACα mutant. We have found that the L205R mutation affects the kinetics of both Kemptide and ATP as substrates, decreasing the catalytic efficiency (kcat/KM) for each substrate by 12‐fold and 4.5‐fold, respectively. We have also determined the IC50 and Ki for the peptide substrate‐competitive inhibitor PKI(5–24) and the ATP‐competitive inhibitor H89. The L205R mutation had no effect on the potency of H89, but causes a \u3e 250‐fold loss in potency for PKI(5–24). Collectively, these data provide insights for the development of L205R‐PKACα inhibitors as potential therapeutics

Applying the partial credit method of Rasch analysis: language testing and accountability

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68583/2/10.1177_026553228900600109.pd

Cannabinoid receptor interacting protein suppresses agonist-driven CB1 receptor internalization and regulates receptor replenishment in an agonist-biased manner

Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that modulates CB1R signaling via G proteins, and CB1R down-regulation but not desensitization (Blume et al. [2015] Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In this study, we determined the involvement of CRIP1a in CB1R plasma membrane trafficking. To follow the effects of agonists and antagonists on cell surface CB(1)Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2, which endogenously expresses both CB1R and CRIP1a, and exhibits a well-characterized endocannabinoid signaling system. We developed stable CRIP1a-over-expressing and CRIP1a-siRNA-silenced knockdown clones to investigate gene dose effects of CRIP1a on CB1R plasma membrane expression. Results indicate that CP55940 or WIN55212-2 (10 nM, 5 min) reduced cell surface CB1R by a dynamin-and clathrin-dependent process, and this was attenuated by CRIP1a over-expression. CP55940-mediated cell surface CB1R loss was followed by a cycloheximide-sensitive recovery of surface receptors (30120 min), suggesting the requirement for new protein synthesis. In contrast, WIN55212-2-mediated cell surface CB(1)Rs recovered only in CRIP1a knockdown cells. Changes in CRIP1a expression levels did not affect a transient rimonabant (10 nM)mediated increase in cell surface CB(1)Rs, which is postulated to be as a result of rimonabant effects on \u27non-agonist-driven\u27 internalization. These studies demonstrate a novel role for CRIP1a in agonist-driven CB1R cell surface regulation postulated to occur by two mechanisms: 1) attenuating internalization that is agonist-mediated, but not that in the absence of exogenous agonists, and 2) biased agonist-dependent trafficking of de novo synthesized receptor to the cell surface

Dynamical percolation on general trees

H\"aggstr\"om, Peres, and Steif (1997) have introduced a dynamical version of percolation on a graph $G$. When $G$ is a tree they derived a necessary and sufficient condition for percolation to exist at some time $t$. In the case that $G$ is a spherically symmetric tree, H\"aggstr\"om, Peres, and Steif (1997) derived a necessary and sufficient condition for percolation to exist at some time $t$ in a given target set $D$. The main result of the present paper is a necessary and sufficient condition for the existence of percolation, at some time $t\in D$, in the case that the underlying tree is not necessary spherically symmetric. This answers a question of Yuval Peres (personal communication). We present also a formula for the Hausdorff dimension of the set of exceptional times of percolation.Comment: 24 pages; to appear in Probability Theory and Related Field

Associations between children's diet quality and watching television during meal or snack consumption: a systematic review

Studies have identified an association between watching television (TV) and childhood obesity. This review adds context to existing research by examining the associations between TV viewing, whilst eating, and children's diet quality. Web of Science and PubMed databases were searched from January 2000 to June 2014. Cross-sectional trials of case control or cohort studies, which included baseline data, measuring the associations between eating whilst watching TV and children's food and drink intake. Quality of selected papers was assessed. Thirteen studies, representing 61,674 children aged 1–18 yrs, met inclusion criteria. Of six studies reporting overall food habits, all found a positive association between TV viewing and consumption of pizza, fried foods, sweets, and snacks. Of eight studies looking at fruit and vegetable consumption, seven identified a negative association with eating whilst watching TV (p < .0001). Four out of five studies identified a positive association between watching TV whilst eating and servings of sugar-sweetened beverages (p < .0001). Four studies identified an association between low socioeconomic status and increased likelihood of eating whilst watching TV (p ≤ .01). Family meals did not overcome the adverse impact on diet quality of having the TV on at mealtimes. Eating whilst watching television is associated with poorer diet quality among children, including more frequent consumption of sugar-sweetened beverages and high-fat, high-sugar foods and fewer fruits and vegetables. Although these differences in consumption are small, the cumulative effect may contribute to the positive association between eating whilst watching TV and childhood obesity

Prediction of lignin content in ruminant diets and faecal samples using rapid analytical techniques

The measurement of lignin content in ruminant diet and faecal samples is important for 2 digestibility studies, but it is typically time consuming and costly. The work reported 3 involved correlation of traditional wet chemistry data with that from three rapid instrumental 4 techniques, Fourier Transform Infrared spectroscopy (FTIR), Conventional 5 Thermogravimteric Analysis (TGA) and High Resolution TGA (MaxRes TGA) to predict 6 lignin content of diets and faeces from digestibility trials. Calibration and performance data 7 indicated that the FTIR model was acceptable for screening whilst the Conventional and 8 MaxRes TGA predictions were of high accuracy for quantitative analysis. Cross validation 9 and model performance data revealed that MaxRes TGA provided the best performing 10 predictive model. This work showed that MaxRes TGA can accurately predict lignin content 11 in ruminant diet and faecal samples with distinct advantages over traditional wet chemistry, 12 namely the requirement for small sample size, ease of sample preparation, speed of analysis 13 and high sample throughput at considerably lower cost

G-Brownian Motion as Rough Paths and Differential Equations Driven by G-Brownian Motion

The present paper is devoted to the study of sample paths of G-Brownian motion and stochastic differential equations (SDEs) driven by G-Brownian motion from the view of rough path theory. As the starting point, we show that quasi-surely, sample paths of G-Brownian motion can be enhanced to the second level in a canonical way so that they become geometric rough paths of roughness 2 < p < 3. This result enables us to introduce the notion of rough differential equations (RDEs) driven by G-Brownian motion in the pathwise sense under the general framework of rough paths. Next we establish the fundamental relation between SDEs and RDEs driven by G-Brownian motion. As an application, we introduce the notion of SDEs on a differentiable manifold driven by GBrownian motion and construct solutions from the RDE point of view by using pathwise localization technique. This is the starting point of introducing G-Brownian motion on a Riemannian manifold, based on the idea of Eells-Elworthy-Malliavin. The last part of this paper is devoted to such construction for a wide and interesting class of G-functions whose invariant group is the orthogonal group. We also develop the Euler-Maruyama approximation for SDEs driven by G-Brownian motion of independent interest