Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.This work was supported by the Biotechnology and Biological Sciences Research Council and by the Wellcome Trust.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100514

Role for zinc transporter gene SLC39A12 in the nervous system and beyond

The SLC39A12 gene encodes the zinc transporter protein ZIP12, which is expressed across many tissues and is highly abundant in the vertebrate nervous system. As a zinc transporter, ZIP12 functions to transport zinc across cellular membranes, including cellular zinc influx across the plasma membrane. Genome-wide association and exome sequencing studies have shown that brain susceptibility-weighted magnetic resonance imaging (MRI) intensity is associated with ZIP12 polymorphisms and rare mutations. ZIP12 is required for neural tube closure and embryonic development in Xenopus tropicalis. Frog embryos depleted of ZIP12 by antisense morpholinos develop an anterior neural tube defect and lack viability. ZIP12 is also necessary for neurite outgrowth and mitochondrial function in mouse neural cells. ZIP12 mRNA is increased in brain regions of schizophrenic patients. Outside of the nervous system, hypoxia induces ZIP12 expression in multiple mammalian species, including humans, which leads to endothelial and smooth muscle thickening in the lung and contributes towards pulmonary hypertension. Other studies have associated ZIP12 with other diseases such as cancer. Given that ZIP12 is highly expressed in the brain and that susceptibility-weighted MRI is associated with brain metal content, ZIP12 may affect neurological diseases and psychiatric illnesses such as Parkinson's disease, Alzheimer's disease, and schizophrenia. Furthermore, the induction of ZIP12 and resultant zinc uptake under pathophysiological conditions may be a critical component of disease pathology, such as in pulmonary hypertension. Drug compounds that bind metals like zinc may be able to treat diseases associated with impaired zinc homeostasis and altered ZIP12 function.Human Sciences Research and Graduate StudiesGraduate CollegeNutritional Science

An elasto-plastic self-consistent model for damaged polycrystalline materials: Theoretical formulation and numerical implementation

Elasto-plastic multiscale approaches are known to be suitable to model the mechanical behavior of metallic materials during forming processes. These approaches are classically adopted to explicitly link relevant microstructural effects to the macroscopic behavior. This paper presents a finite strain elastoplastic self-consistent model for damaged polycrystalline aggregates and its implementation into ABAQUS/Standard finite element (FE) code. Material degradation is modeled by the introduction of a scalar damage variable at each crystallographic slip system for each individual grain. The single crystal plastic flow is described by both the classical and a regularized version of the Schmid criterion. To integrate the single crystal constitutive equations, two new numerical algorithms are developed (one for each plastic flow rule). Then, the proposed single crystal modeling is embedded into the self-consistent scheme to predict the mechanical behavior of elasto-plastic polycrystalline aggregates in the finite strain range. This strategy is implemented into ABAQUS/Standard FE code through a user-defined material (UMAT) subroutine. Special attention is paid to the satisfaction of the incremental objectivity and the efficiency of the convergence of the global resolution scheme, related to the computation of the consistent tangent modulus. The capability of the new constitutive modeling to capture the interaction between the damage evolution and the microstructural properties is highlighted through several simulations at both single crystal and polycrystalline scales. It appears from the numerical tests that the use of the classical Schmid criterion leads to a poor numerical convergence of the self-consistent scheme (due to the abrupt changes in the activity of the slip systems), which sometimes causes the computations to be prematurely stopped. By contrast, the use of the regularized version of the Schmid law allows a better convergence of the self-consistent approach, but induces an important increase in the computation time devoted to the integration of the single crystal constitutive equations (because of the high value of the power-law exponent used to regularize the Schmid yield function). To avoid these difficulties, a numerical strategy is built to combine the benefits of the two approaches: the classical Schmid criterion is used to integrate the single crystal constitutive equations, while its regularized version is used to compute the microscopic tangent modulus required for solving the self-consistent equations. The robustness and the accuracy of this novel numerical strategy are particularly analyzed through several numerical simulations (prediction of the mechanical behavior of polycrystalline aggregates and simulation of a circular cup-drawing forming process)

Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal interposition surgery in UCD-T2DM rats

Post-operative increases in circulating bile acids have been suggested to contribute to the metabolic benefits of bariatric surgery; however, their mechanistic contributions remain undefined. We have previously reported that ileal interposition (IT) surgery delays the onset of type 2 diabetes in UCD-T2DM rats and increases circulating bile acids, independently of effects on energy intake or body weight. Therefore, we investigated potential mechanisms by which post-operative increases in circulating bile acids improve glucose homeostasis after IT surgery. IT, sham or no surgery was performed on 2-month-old weight-matched male UCD-T2DM rats. Animals underwent an oral fat tolerance test (OFTT) and serial oral glucose tolerance tests (OGTT). Tissues were collected at 1.5 and 4.5 months after surgery. Cell culture models were used to investigate interactions between bile acids and ER stress. IT-operated animals exhibited marked improvements in glucose and lipid metabolism, with concurrent increases in postprandial glucagon-like peptide-1 (GLP-1) secretion during the OFTT and OGTTs, independently of food intake and body weight. Measurement of circulating bile acid profiles revealed increases in circulating total bile acids in IT-operated animals, with a preferential increase in circulating cholic acid concentrations. Gut microbial populations were assessed as potential contributors to the increases in circulating bile acid concentrations, which revealed proportional increases in Gammaproteobacteria in IT-operated animals. Furthermore, IT surgery decreased all three sub-arms of ER stress signaling in liver, adipose and pancreas tissues. Amelioration of ER stress coincided with improved insulin signaling and preservation of β-cell mass in IT-operated animals. Incubation of hepatocyte, adipocyte and β-cell lines with cholic acid decreased ER stress. These results suggest that postoperative increases in circulating cholic acid concentration contribute to improvements in glucose homeostasis after IT surgery by ameliorating ER stress

Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal interposition surgery in UCD-T2DM rats

Post-operative increases in circulating bile acids have been suggested to contribute to the metabolic benefits of bariatric surgery; however, their mechanistic contributions remain undefined. We have previously reported that ileal interposition (IT) surgery delays the onset of type 2 diabetes in UCD-T2DM rats and increases circulating bile acids, independently of effects on energy intake or body weight. Therefore, we investigated potential mechanisms by which post-operative increases in circulating bile acids improve glucose homeostasis after IT surgery. IT, sham or no surgery was performed on 2-month-old weight-matched male UCD-T2DM rats. Animals underwent an oral fat tolerance test (OFTT) and serial oral glucose tolerance tests (OGTT). Tissues were collected at 1.5 and 4.5 months after surgery. Cell culture models were used to investigate interactions between bile acids and ER stress. IT-operated animals exhibited marked improvements in glucose and lipid metabolism, with concurrent increases in postprandial glucagon-like peptide-1 (GLP-1) secretion during the OFTT and OGTTs, independently of food intake and body weight. Measurement of circulating bile acid profiles revealed increases in circulating total bile acids in IT-operated animals, with a preferential increase in circulating cholic acid concentrations. Gut microbial populations were assessed as potential contributors to the increases in circulating bile acid concentrations, which revealed proportional increases in Gammaproteobacteria in IT-operated animals. Furthermore, IT surgery decreased all three sub-arms of ER stress signaling in liver, adipose and pancreas tissues. Amelioration of ER stress coincided with improved insulin signaling and preservation of β-cell mass in IT-operated animals. Incubation of hepatocyte, adipocyte and β-cell lines with cholic acid decreased ER stress. These results suggest that postoperative increases in circulating cholic acid concentration contribute to improvements in glucose homeostasis after IT surgery by ameliorating ER stress

On the elasto-viscoplastic behavior of the Ti5553 alloy

The elastoviscoplastic behavior of the Ti5553 alloy is characterized and compared to the classical Ti–6Al–4V alloy. The true stress–strain curves are determined based on tensile tests performed under different strain rates at room temperature and at 1501C, from which the elastic constants and the parameters of a Norton–Hoff viscoplastic model are identified. The strength of the Ti5553 alloy is 20–40% higher than the strength of the Ti–6Al–4V alloy. The Ti5553 alloy constitutes thus a promising candidate for advanced structural applications. In view of modeling structural applications of forming operations, the elastic and plastic initial anisotropy of the two alloys is investigated by combining compression on cylinders with elliptical sections, uniaxial tensile tests in different material directions, plane strain and shear tests. The initial anisotropy of the different alloys is very weak which justifies the modeling of the mechanical behavior with an isotropic yield surface. The identified elastoviscoplastic model is validated by comparing experimental results with FE predictions both on cylindrical notched specimens subjected to tensile tests and onflat specimens subjected to plane strain conditions

Oral manifestations of thrombocytopaenia

The appearance in the mouth of haemorrhagic petechiae, ecchymoses or blood blisters with spontaneous bleeding is suggestive of a haemorrhagic disorder that may be caused either by functional impairment of platelets or of blood vessel walls, by an abnormal decrease in the number of circulating platelets (thrombocytopaenia), or by defects in the blood clotting mechanism. Thrombocytopaenia from decreased production or increased destruction of platelets may be caused by multiple factors including immune mediated mechanisms, drugs or infections. A diagnosis of thrombocytopaenic purpura can be made when any other disease entity that might be causing the purpura is excluded on the basis of the medical history, the physical examination, a complete blood count and a peripheral blood smear. In this paper, we outline the clinical features of oral thrombocytopaenic purpura and briefly discuss some aspects of its aetiopathogenesis and treatment

Zn treatment effects on biological potential of fennel bulbs as affected by in vitro digestion process

Zn treatment effects on the stability of polyphenols, MDA (malondialdehyde) content, antioxidant and lipoxygenase inhibition activities of two varieties of fennel bulbs were studied by using an in vitro gastrointestinal digestion model. Likewise, the effect of Zn on viability cells of E. coli was also performed. The results revealed that high amounts of total phenolic and flavonoid compounds were released during the digestion process, especially after the intestinal phase. Additionally, the antioxidant and lipoxygenase inhibitory activity were affected by the gastrointestinal digestion process and seems to be correlated with total phenol contents. On the other hand, the viability of E. coli was not affected by the activity of our tested bulbs during passage through the artificial digestion model, but the treated bulbs activity contribute relatively to the inhibition growth of bacteria. The survival of E. coli in fennel bulbs was challenged with simulated gastrointestinal fluids and the results showed that the E. coli strains, despite having experienced a viability reduction at the intestinal phase, were able to overcome the exposure to the gastrointestinal synthetic fluids. This E. coli ability reinforces the need for good hygienic measures to assure safe fresh produce, even for those that are rich in antibacterial compounds.info:eu-repo/semantics/publishedVersio