Dietary selenium affects intestinal development of Eimeria papillata in mice

Here, we investigated the effect of the trace element selenium (Se) on course and outcome of Eimeria-paplllata-induced coccidiosis in mice. Male mice were fed on Se-adequate (0.15 ppm), Se-deficient, and Se-high diets (1.0 ppm) for 6 weeks. Mice were orally infected with 1,000 oocysts. The prepatent period lasts for 3 days, but the course of infections varied. At Se-adequate diet, the maximum fecal output of oocysts amounted to 68,300 ooccysts/g feces on day 5 p.i.. However, fecal shedding of oocysts was accelerated in mice on Se-deficient diet and occurred already on day 4 p.i.. By contrast, maximal shedding is impaired in mice on high-Se diet, which takes place on day 5 p.i., but with a decreased output of only 7,300 oocysts/g feces. Light microscopy reveals that all developmental stages are affected: meronts, micro- and macrogamonts, and developing oocysts are increased in comparison with mice fed on selenium-adequate diet. At high Se, the number of parasitic stages in the jejunum is substantially higher than at Se-deficient diet. Se does not affect the number of jejunal Alcian blue-stained goblet cells. Se deficiency increased the number of apoptotic cells in the jejunum. Substantially increased histological injury scores reveal more injuries in jejunum tissue infected by E. papillata. Our data indicate that high dietary Se exerts potential anticoccidial activity. This may be taken advantage of in control measures towards Eimeriosis as a feed additive, potentially alleviating the need for concomitantly utilized anti-coccidial drugs in the feed.     

The potential impact of the pulmonary microbiome on immunopathogenesis of Aspergillus‐related lung disease

Aspergillosis is an infection or allergic response caused by fungi of the genus Aspergillus. The most common forms of aspergillosis are allergic bronchopulmonary aspergillosis, chronic pulmonary aspergillosis, and invasive pulmonary aspergillosis. Aspergillus also plays an important role in fungal sensitized asthma. Humans inhale Aspergillus spores every day and when the host is immunocompromised, Aspergillus spp. may cause severe pulmonary disease. There is increasing evidence that the microbiome plays a significant role in immune regulation, chronic inflammatory diseases, metabolism, and other physiological processes, including recovery from the effects of antibiotic treatment. Bacterial microbiome mediated resistance mechanisms probably play a major role in limiting fungal colonization of the lungs, and may therefore prevent humans from contracting Aspergillus‐related diseases. In this perspective, we review this emerging area of research and discuss the role of the microbiome in aspergillosis, role of Aspergillus in the microbiome, and the influence of the microbiome on anti‐Aspergillus host defense and its role in preventing aspergillosis.     

DhhP,a Cyclic di-AMP Phosphodiesterase of Borrelia burgdorferi,Is Essential for Cell Growth and Virulence

Cyclic di-AMP (c-di-AMP) is a recently discovered second messenger in bacteria. Most of work on c-di-AMP signaling has been done in Gram-positive bacteria, firmicutes, and actinobacteria, where c-di-AMP signaling pathways affect potassium transport, cell wall structure, and antibiotic resistance. Little is known about c-di-AMP signaling in other bacteria. Borrelia burgdorferi, the causative agent of Lyme disease, is a spirochete that has a Gram-negative dual membrane. In this study, we demonstrated that B. burgdorferi BB0619, a DHH-DHHA1 domain protein (herein designated DhhP), functions as c-di-AMP phosphodiesterase. Recombinant DhhP hydrolyzed c-di-AMP to pApA in a Mn²⁺- or Mg²⁺-dependent manner. In contrast to c-di-AMP phosphodiesterases reported thus far, DhhP appears to be essential for B. burgdorferi growth both in vitro and in the mammalian host. Inactivation of the chromosomal dhhP gene could be achieved only in the presence of a plasmid-encoded inducible dhhP gene. The conditional dhhP mutant had a dramatic increase in intracellular c-di-AMP level in comparison to the isogenic wild-type strain. Unlike what has been observed in Gram-positive bacteria, elevated cellular c-di-AMP in B. burgdorferi did not result in an increased resistance to β-lactamase antibiotics, suggesting that c-di-AMP''s functions in spirochetes differ from those in Gram-positive bacteria. In addition, the dhhP mutant was defective in induction of the σ^S factor, RpoS, and the RpoS-dependent outer membrane virulence factor OspC, which uncovers an important role of c-di-AMP in B. burgdorferi virulence.     

A Novel Testing Platform for Assessing Knee Joint Mechanics: A Parallel Robotic System Combined with an Instrumented Spatial Linkage

Assessing joint function following trauma and its inter-relation with degenerative changes requires an understanding of the normal state of structural loading in the joint. Very few studies have attempted to reproduce joint specific in vivo motions in vitro to quantify the actual loads carried by different tissues within the knee joint. The most significant challenge in this area is the very high sensitivity of the loads in joint structures to motion reproduction accuracy. A novel testing platform for assessing knee joint mechanics is described, comprised of a highly accurate (0.3 ± 0.1 mm, 0.3 ± 0.1°) six-degree-of-freedom (6-DOF) instrumented spatial linkage (ISL) for in vivo joint kinematic assessments and a unique 6-DOF parallel robotic manipulator. A position feedback system (ISL and position controller) is used for accurate reproduction of in vivo joint motions and estimation of “in situ” joint/tissue loads. The parallel robotic manipulator provides excellent stiffness and repeatability in reproducing physiological motions in 6-DOF, compared to the commonly used serial robots. The position feedback system provides real-time feedback data to the robot to reproduce in vivo motions and significantly enhances motion reproduction accuracy by adjusting for robot end-effector movements. Using this combined robot-ISL system, in vivo motions can be reproduced in vitro with very high accuracy (0.1 mm, 0.1°). Our results indicate that this level of accuracy is essential for meaningful estimation of tissue loads during gait. Using this novel testing platform, we have determined the normal load-carrying characteristics of different tissues within the ovine knee joint. The application of this testing system will continue to increase our understanding of normal and pathological joint states.     

Autosomal-dominant nystagmus,foveal hypoplasia and presenile cataract associated with a novel PAX6 mutation

Autosomal-dominant idiopathic infantile nystagmus has been linked to 6p12 (OMIM 164100), 7p11.2 (OMIM 608345) and 13q31-q33 (OMIM 193003). PAX6 (11p13, OMIM 607108) mutations can also cause autosomal-dominant nystagmus, typically in association with aniridia or iris hypoplasia. We studied a large multigenerational white British family with autosomal-dominant nystagmus, normal irides and presenile cataracts. An SNP-based genome-wide analysis revealed a linkage to a 13.4-MB region on chromosome 11p13 with a maximum lod score of 2.93. A mutation analysis of the entire coding region and splice junctions of the PAX6 gene revealed a novel heterozygous missense mutation (c.227C>G) that segregated with the phenotype and is predicted to result in the amino-acid substitution of proline by arginine at codon 76 p.(P76R). The amino-acid variation p.(P76R) within the paired box domain is likely to destabilise the protein due to steric hindrance as a result of the introduction of a polar and larger amino acid. Eye movement recordings showed a significant intrafamilial variability of horizontal, vertical and torsional nystagmus. High-resolution in vivo imaging of the retina using optical coherence tomography (OCT) revealed features of foveal hypoplasia, including rudimentary foveal pit, incursion of inner retinal layers, short photoreceptor outer segments and optic nerve hypoplasia. Thus, this study presents a family that segregates a PAX6 mutation with nystagmus and foveal hypoplasia in the absence of iris abnormalities. Moreover, it is the first study showing detailed characteristics using eye movement recordings of autosomal-dominant nystagmus in a multigenerational family with a novel PAX6 mutation.