Herpesvirus Regulation of Selective Autophagy

Selective autophagy has emerged as a key mechanism of quality and quantity control responsible for the autophagic degradation of specific subcellular organelles and materials. In addition, a specific type of selective autophagy (xenophagy) is also activated as a line of defense against invading intracellular pathogens, such as viruses. However, viruses have evolved strategies to counteract the host’s antiviral defense and even to activate some proviral types of selective autophagy, such as mitophagy, for their successful infection and replication. This review discusses the current knowledge on the regulation of selective autophagy by human herpesviruses.     

Percutaneous Closure of Aortic and Mitral Paravalvular Leaks—Diagnostic and Therapeutic Considerations

Purpose of review

Prenatal diagnosis of congenital heart disease (CHD) is continuously evolving with each passing decade. Early efforts in fetal cardiology focused on identifying CHD in mid-gestation and understanding of fetal circulation in pathologic conditions. Improving prenatal detection rates for CHD remains an ongoing challenge and increasingly the field of fetal cardiology is moving to not only diagnosing CHD prenatally but also assessing the impact of prenatal diagnosis of CHD outcomes. Future directions include earlier diagnosis of fetal CHD, improved diagnostic rates, widespread sonographer education, and a better understanding of antenatal factors that impact outcomes. Our goal in this review is to describe the past, present, and future of prenatal diagnosis of CHD.

Recent findings

There has been a steady improvement in the prenatal diagnosis rate for CHD; however, there remains a significant variation between countries and within the USA. Prenatal diagnosis of CHD allows for counseling and delivery planning in those fetuses with critical CHD, thereby providing parents with resources and important tools while dealing with a challenging situation of carrying a child with heart disease and helping them with important decisions for their family and their future. There are several specific conditions which continue to pose a challenge from a diagnostic standpoint as they may appear mild at the time of initial diagnosis and may be missed but progress through the pregnancy and lead to significant CHD in the neonatal period.

Summary

In summary, continued efforts aimed at collaborative research and education are needed in order to be able to improve CHD detection rates. We need to cautiously assess lesions that appear minor in mid-gestation but have the potential to progress in late gestation. Earlier detection of CHD by means of a transvaginal or a first-trimester fetal echocardiogram may further help families with delivery planning and decision-making.

     

New dianthramide and cinnamic ester glucosides from the roots of Aconitum carmichaelii

Four new compounds N-salicyl-3-hydroxyanthranilic acid methyl ester (1), N-(2′-dehydroxysalicyl)-3-hydroxyanthranilic acid methyl ester (2), methyl-4-β-D-allopyranosyl-ferulate (3), and methyl-4-β-D-gulopyranosyl-cinnamate (4), along with six known compounds (5–10), were isolated from the roots of Aconitum carmichelii Debx. Their structures were elucidated on the basis of spectral data analysis, including 1D, 2D-NMR, and HR-ESI-MS. Compounds 1 and 2 showed the inhibition of nitric oxide (NO) production with IC₅₀ values of 9.13 and 19.94 μM, respectively.     

Phylogenetic and Phylogeographic Analyses of Porcine Circovirus Type 2 Among Pig Farms in Vietnam

This study demonstrated the prevalence of Porcine circovirus type 2 (PCV2) among pig farms in Vietnam. Analyses of the genome, capsid protein and phylogeny classified all 30 Vietnamese PCV2 strains as the PCV2b genotype, belonging to the clusters of 1A, 1B, 1C and recombinant forms. Each viral genome was 1767 nucleotides long and shared 96.0–100% nucleotide sequence identity. The amino acid substitutions in the capsid protein of the Vietnamese PCV2 strains were in immunodominant regions, and the majority of strains (24/30) contained a lysine extension at the C‐terminus. Bayesian phylogeographic analysis revealed epidemic links of the PCV2 recombinant cluster within and among countries, which supports a circulating recombinant form of PCV2. Further analysis by the Jameson–Wolf antigenic index indicated antigenic alterations at important sites in the capsid protein (sites 131–133) among the recombinant cluster and the other clusters of PCV2b.     

Independent component analysis of resting state activity in pediatric obsessive‐compulsive disorder

Obsessive‐compulsive disorder (OCD) is an often severely disabling illness with onset generally in childhood or adolescence. Little is known, however, regarding the pattern of brain resting state activity in OCD early in the course of illness. We therefore examined differences in brain resting state activity in patients with pediatric OCD compared with healthy volunteers and their clinical correlates. Twenty‐three pediatric OCD patients and 23 healthy volunteers (age range 9–17), matched for sex, age, handedness, and IQ completed a resting state functional magnetic resonance imaging exam at 3T. Patients completed the Children's Yale Brown Obsessive Scale. Data were decomposed into 36 functional networks using spatial group independent component analysis (ICA) and logistic regression was used to identify the components that yielded maximum group separation. Using ICA we identified three components that maximally separated the groups: a middle frontal/dorsal anterior cingulate network, an anterior/posterior cingulate network, and a visual network yielding an overall group classification of 76.1% (sensitivity = 78.3% and specificity = 73.9%). Independent component expression scores were significantly higher in patients compared with healthy volunteers in the middle frontal/dorsal anterior cingulate and the anterior/posterior cingulate networks, but lower in patients within the visual network. Higher expression scores in the anterior/posterior cingulate network correlated with greater severity of compulsions among patients. These findings implicate resting state fMRI abnormalities within the cingulate cortex and related control regions in the pathogenesis and phenomenology of OCD early in the course of the disorder and prior to extensive pharmacologic intervention. Hum Brain Mapp 35:5306–5315, 2014. © 2014 Wiley Periodicals, Inc.     

Regional brain metabolism in a murine systemic lupus erythematosus model

Systemic lupus erythematosus (SLE) is characterized by multiorgan inflammation, neuropsychiatric disorders (NPSLE), and anti-nuclear antibodies. We previously identified a subset of anti-DNA antibodies (DNRAb) cross-reactive with the N-methyl-D-aspartate receptor, present in 30% to 40% of patients, able to enhance excitatory post-synaptic potentials and trigger neuronal apoptosis. DNRAb+ mice exhibit memory impairment or altered fear response, depending on whether the antibody penetrates the hippocampus or amygdala. Here, we used 18F-fluorodeoxyglucose (FDG) microPET to plot changes in brain metabolism after regional blood–brain barrier (BBB) breach. In DNRAb+ mice, metabolism declined at the site of BBB breach in the first 2 weeks and increased over the next 2 weeks. In contrast, DNRAb− mice exhibited metabolic increases in these regions over the 4 weeks after the insult. Memory impairment was present in DNRAb+ animals with hippocampal BBB breach and altered fear conditioning in DNRAb+ mice with amygdala BBB breach. In DNRAb+ mice, we observed an inverse relationship between neuron number and regional metabolism, while a positive correlation was observed in DNRAb− mice. These findings suggest that local metabolic alterations in this model take place through different mechanisms with distinct time courses, with important implications for the interpretation of imaging data in SLE subjects.     

Induction of rainbow trout MH class I and accessory proteins by viral haemorrhagic septicaemia virus

Major histocompatibility (MH) class I receptors are glycoproteins which play a critical role during responses to intracellular pathogens by presenting endogenous peptides to cytotoxic T cell lymphocytes (CD8+). To date, little is known about MH class I regulation at the protein level during viral infections in fish. In this study, we characterised the MH class I pathway response to polyinosinic–polycytidylic acid (poly I:C) and upon infection with viral haemorrhagic septicemia virus (VHSV) genotype IVa using the rainbow trout monocyte/macrophage cell line RTS11. A 14-day challenge with VHSV IVa at 14 °C demonstrated enhanced expression of the class I heavy chain, β2 microglobulin (β2M) and tapasin, while the expression of other accessory molecules ERp57 and calreticulin remained unchanged. However, when infection occurred at 2 °C no change in expression levels of any of these molecules was observed. β2M accumulated in the media of RTS11 over time, however the β2M concentrations were 2 fold higher in cultures infected with VHSV 14 days post infection. Strikingly, when cells were maintained at 2 °C the secretion of β2M was significantly reduced in both infected and non-infected cultures. These results indicate that VHSV infection alters the kinetics of β2M release as well as the expression of MH class I and suggests that cellular immunity against VHSV can be compromised at low temperatures which may increase host susceptibility to this virus during the winter.