Specific pathogen-free macaques: definition, history, and current production

Specific pathogen-free (SPF) macaque colonies are now requested frequently as a resource for research. Such colonies were originally conceived as a means to cull diseased animals from research-dedicated colonies, with the goal of eliminating debilitating or fatal infectious agents from the colony to improve the reproductive capacity of captive research animals. The initial pathogen of concern was Mycobacterium tuberculosis (M.tb.), recognized for many years as a pathogen of nonhuman primates as well as a human health target. More recently attention has focused on four viral pathogens as the basis for an SPF colony: simian type D retrovirus (SRV), simian immunodeficiency virus (SIV), simian T cell lymphotropic/leukemia virus (STLV), and Cercopithecine herpesvirus 1 (CHV-1). New technologies, breeding, and maintenance schemes have emerged to develop and provide SPF primates for research. In this review we focus on the nonhuman primates (NHPs) most common to North American NHP research facilities, Asian macaques, and the most common current research application of these animals, modeling of human AIDS.     

A new species of Heth Cobb, 1898 (Nematoda: Rhigonematida: Hethidae) from an Australian millipede (Myriapoda: Diplopoda: Spirostreptida)

Abstract

A new species of nematode, Heth baudini sp. n. from a diplopod (Spirostreptida: Iulomorphidae Verhoeff, 1924) collected in Queensland, Australia, is described and illustrated. The cephalic and cervical cuticular ornamentation of females of H. baudini sp. n. is similar to those of South-East Asian and Australasian Heth species. Heth baudini sp. n. females are particularly close to Heth taynguyeni from Vietnam but can be distinguished by the shape of the lateral lappets, which in H. taynguyeni limit the trapezium-shaped region of smooth cuticle unlike the elliptical region in H. baudini sp. n., and by the presence of lateral spines only half the size. The cuticle of the H. baudini sp. n. is finely annulated along the entire body, whereas H. taynguyeni has broader rings behind the first pair of lateral spines, each consisting of five or six narrower rings separated from each other by deeper furrows. Males of H. baudini sp. n. are characterised by the presence of a bursa-like fold on the tail and can be distinguished from other species of the genus by the presence of somatic papillae embedded into the bursal fold.     

Avian-type receptor-binding ability can increase influenza virus pathogenicity in macaques

The first influenza pandemic of the 21st century was caused by novel H1N1 viruses that emerged in early 2009. An Asp-to-Gly change at position 222 of the receptor-binding protein hemagglutinin (HA) correlates with more-severe infections in humans. The amino acid at position 222 of HA contributes to receptor-binding specificity with Asp (typically found in human influenza viruses) and Gly (typically found in avian and classic H1N1 swine influenza viruses), conferring binding to human- and avian-type receptors, respectively. Here, we asked whether binding to avian-type receptors enhances influenza virus pathogenicity. We tested two 2009 pandemic H1N1 viruses possessing HA-222G (isolated from severe cases) and two viruses that possessed HA-222D. In glycan arrays, viruses possessing HA-222D preferentially bound to human-type receptors, while those encoding HA-222G bound to both avian- and human-type receptors. This difference in receptor binding correlated with efficient infection of viruses possessing HA-222G, compared to those possessing HA-222D, in human lung tissue, including alveolar type II pneumocytes, which express avian-type receptors. In a nonhuman primate model, infection with one of the viruses possessing HA-222G caused lung damage more severe than did infection with a virus encoding HA-222D, although these pathological differences were not observed for the other virus pair with either HA-222G or HA-222D. These data demonstrate that the acquisition of avian-type receptor-binding specificity may result in more-efficient infection of human alveolar type II pneumocytes and thus more-severe lung damage. Collectively, these findings suggest a new mechanism by which influenza viruses may become more pathogenic in mammals, including humans.     

Effect of Paricalcitol vs Calcitriol on Hemoglobin Levels in Chronic Kidney Disease Patients: A Randomized Trial

Background

Recent studies suggest that vitamin D deficiency represents an additional cofactor of renal anemia, with several mechanisms accounting for this relationship. In line with it, the administration of vitamin D or its analogues has been associated with an improvement of anemia. There are no data, however, about a direct effect of paricalcitol on hemoglobin (Hb) levels. Therefore, we conducted a study to determine whether paricalcitol, compared to calcitriol, improves anemia in patients with chronic kidney disease (CKD).

Methods

In this randomized trial 60 CKD patients stage 3b-5 and anemia (Hb levels: 10-12.5 g/dL) were assigned (1:1) to receive low doses of calcitriol (Group Calcitriol) or paricalcitol (Group Paricalcitol) for 6 months. All the patients had normal values of plasma calcium, phosphorus and PTH, a stable iron balance, and normal values of C-Reactive Protein. The primary endpoint was to evaluate the effects of the two treatments on Hb levels; the modifications in 24hr-proteinuria (UProt) were also evaluated.

Results

A significant Group x Time interaction effect was observed in the longitudinal analysis of Hb levels (F(1,172)=31.4, p<0.001). Subjects in Paricalcitol experienced a significant monthly increase of Hb levels equal to +0.16 g/dL [95% C.I. 0.10 to +0.22, p<0.001) while in Group Calcitriol, Hb decrease throughout the follow-up with an average monthly rate of -0.10 g/dL (95% C.I.: -0.17 to -0.04, p<0.001). In Group Paricalcitol, UProt was significantly reduced after 6 months [0.35 (0.1-1.2) vs 0.59 (0.2-1.6), p<0.01], whereas no significant difference emerged in Group Calcitriol. Plasma levels of calcium, phosphate, PTH and of inflammation markers remained in the normal range in both groups throughout the study.

Conclusions

Short-term exposure to paricalcitol results in an independent increase in Hb levels, which occurred with no modification of iron balance, inflammatory markers, and PTH plasma concentrations, and was associated with a decrease in UProt.

Trial Registration

ClinicalTrials.gov NCT01768351     

Tight control of mitochondrial membrane potential by cytochrome c oxidase

In the present work we have critically examined the use of the KCN-titration technique in the study of the control of the cellular respiration by cytochrome c oxidase (COX) in the presence of the mitochondrial membrane potential (Δψ(mito)) in HepG2 cells. We clearly show that the apparent high inhibition threshold of COX in the presence of maximal Δψ(mito) is due to the KCN-induced decrease of Δψ(mito) and not to a low control of COX on the mitochondrial respiration. The tight control exerted by COX on the Δψ(mito) provides further insights for understanding the pathogenetic mechanisms associated with mitochondrial defects in human neuromuscular degenerative disorders.     

A novel synthetic peptide from a tomato defensin exhibits antibacterial activities against Helicobacter pylori

Defensins are a class of cysteine‐rich proteins, which exert broad spectrum antimicrobial activity. In this work, we used a bioinformatic approach to identify putative defensins in the tomato genome. Fifteen proteins had a mature peptide that includes the well‐conserved tetradisulfide array. We selected a representative member of the tomato defensin family; we chemically synthesized its γ‐motif and tested its antimicrobial activity. Here, we demonstrate that the synthetic peptide exhibits potent antibacterial activity against Gram‐positive bacteria, such as Staphylococcus aureus A170, Staphylococcus epidermidis, and Listeria monocytogenes, and Gram‐negative bacteria, including Salmonella enterica serovar Paratyphi, Escherichia coli, and Helicobacter pylori. In addition, the synthetic peptide shows minimal (<5%) hemolytic activity and absence of cytotoxic effects against THP‐1 cells. Finally, SolyC exerts an anti‐inflammatory activity in vitro, as it downregulates the level of the proinflammatory cytokines TNF‐α and IFN‐γ. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.     

Detailed protein sequence alignment based on Spectral Similarity Score (SSS)

Background  

The chemical property and biological function of a protein is a direct consequence of its primary structure. Several algorithms have been developed which determine alignment and similarity of primary protein sequences. However, character based similarity cannot provide insight into the structural aspects of a protein. We present a method based on spectral similarity to compare subsequences of amino acids that behave similarly but are not aligned well by considering amino acids as mere characters. This approach finds a similarity score between sequences based on any given attribute, like hydrophobicity of amino acids, on the basis of spectral information after partial conversion to the frequency domain.