Global Stability of a MERS-CoV Infection Model with CTL Immune Response and Intracellular Delay

In this paper, we propose and study a Middle East respiratory syndrome coronavirus (MERS-CoV) infection model with cytotoxic T lymphocyte (CTL) immune response and intracellular delay. This model includes five compartments: uninfected cells, infected cells, viruses, dipeptidyl peptidase 4 (DPP4), and CTL immune cells. We obtained an immunity-inactivated reproduction number R0 and an immunity-activated reproduction number R1. By analyzing the distributions of roots of the corresponding characteristic equations, the local stability results of the infection-free equilibrium, the immunity-inactivated equilibrium, and the immunity-activated equilibrium were obtained. Moreover, by constructing suitable Lyapunov functionals and combining LaSalle’s invariance principle and Barbalat’s lemma, some sufficient conditions for the global stability of the three types of equilibria were obtained. It was found that the infection-free equilibrium is globally asymptotically stable if R0≤1 and unstable if R0>1; the immunity-inactivated equilibrium is locally asymptotically stable if R0>1>R1 and globally asymptotically stable if R0>1>R1 and condition (H1) holds, but unstable if R1>1; and the immunity-activated equilibrium is locally asymptotically stable if R1>1 and is globally asymptotically stable if R1>1 and condition (H1) holds

Maternal Obesity in Sheep Increases Fatty Acid Synthesis, Upregulates Nutrient Transporters, and Increases Adiposity in Adult Male Offspring after a Feeding Challenge

<div><p>Maternal obesity in women is increasing worldwide. The objective of this study was to evaluate differences in adipose tissue metabolism and function in adult male offspring from obese and control fed mothers subjected to an <i>ad libitum</i> feeding challenge. We developed a model in which obese ewes were fed 150% of feed provided for controls from 60 days before mating to term. All ewes were fed to requirements during lactation. After weaning, F1 male offspring were fed only to maintenance requirements until adulthood (control = 7, obese = 6), when they were fed <i>ad libitum</i> for 12 weeks with intake monitored. At the end of the feeding challenge offspring were given an intravenous glucose tolerance test (IVGTT), necropsied, and adipose tissue collected. During the feeding trial F1obese males consumed more (P < 0.01), gained more weight (P < 0.01) and became heavier (P < 0.05) than F1control males. During IVGTT, Obese F1 offspring were hyperglycemic and hypoinsulinemic (P < 0.01) compared to F1 control F1. At necropsy perirenal and omental adipose depots weights were 47% and 58% greater respectively and subcutaneous fat thickness 41% greater in F1obese vs F1control males (P < 0.05). Adipocyte diameters were greater (P ≤ 0.04) in perirenal, omental and subcutaneous adipose depots in F1obese males (11, 8 and 7% increase vs. control, respectively). When adipose tissue was incubated for 2 hrs with C-14 labeled acetate, subcutaneous, perirenal, and omental adipose tissue of F1 obese males exhibited greater incorporation (290, 83, and 90% increase vs. control, respectively P < 0.05) of acetate into lipids. Expression of fatty acid transporting, binding, and syntheses mRNA and protein was increased (P < 0.05) compared to F1 control offspring. Maternal obesity increased appetite and adiposity associated with increased adipocyte diameters and increased fatty acid synthesis in over-nourished adult male offspring.</p></div

Western blot analysis measurements of fatty acid translocase (CD 36), fatty acid transporter (FATP) 1 and 4, and insulin-sensitive glucose transporter (GLUT4) protein abundance in perirenal (a), omental (b), mesenteric (c), and subcutaneous (d) adipose tissue of male offspring of control ewes (open histogram; n = 7) fed 100% of NRC recommendations and obese ewes (closed histograms; n = 6) fed 150% of NRC recommendations.

<p>Values are means ± SEM. # means tend to differ (P < 0.10), * treatment differences (P < 0.05) and ** treatment differences (P < 0.01)</p

Messenger RNA abundance of fatty acid synthase and acetyl-CoA carboxylase, nutrient transporters and associated molecules in adipose tissue depots from adult male offspring born to control and obese mothers at necropsy after an <i>ad libitum</i> feeding period

<p>Data are means ± SEM.</p><p>Messenger RNA abundance of fatty acid synthase and acetyl-CoA carboxylase, nutrient transporters and associated molecules in adipose tissue depots from adult male offspring born to control and obese mothers at necropsy after an <i>ad libitum</i> feeding period</p

Biweekly plasma concentrations of glucose (a), insulin (b) and leptin (c) during a feeding challenge of male offspring of control ewes (○, n = 7) fed 100% of NRC recommendations and obese ewes (●, n = 6) fed 150% of NRC recommendations.

<p>Values are means ± SEM. * Mean differences (P < 0.05) and ** mean differences (P < 0.01) at a specific time point between control and obese offspring.</p

Pattern of weight gain during feeding challenge of male offspring of control ewes (○, n = 7) fed 100% of NRC recommendations and obese ewes (●, n = 6) fed 150% of NRC recommendations during gestation.

<p>Values are means ± SEM. Trt P = 0.1669, time P < 0.0001, Trt x time P < 0.0001.* Treatment differences (P < 0.05) and ** Treatment differences (P < 0.01) compared with control.</p