Recurrent herpes zoster in the Shingles Prevention Study: Are second episodes caused by the same varicella-zoster virus strain?

Herpes zoster (HZ) is caused by reactivation of varicella zoster virus (VZV) that established latency in sensory and autonomic neurons during primary infection. In the Shingles Prevention Study (SPS), a large efficacy trial of live attenuated Oka/Merck zoster vaccine (ZVL), PCR-confirmed second episodes of HZ occurred in two of 660 placebo and one of 321 ZVL recipients with documented HZ during a mean follow-up of 3.13 years. An additional two ZVL recipients experienced a second episode of HZ in the Long-Term Persistence Substudy. All episodes of HZ were caused by wild-type VZV. The first and second episodes of HZ occurred in different dermatomes in each of these five participants, with contralateral recurrences in two. Time between first and second episodes ranged from 12 to 28 months. One of the five participants, who was immunocompetent on study enrollment, was immunocompromised at the onset of his first and second episodes of HZ. VZV DNA isolated from rash lesions from the first and second episodes of HZ was used to sequence the full-length VZV genomes. For the unique-sequence regions of the VZV genome, we employed target enrichment of VZV DNA, followed by deep sequencing. For the reiteration regions, we used PCR amplification and Sanger sequencing. Our analysis and comparison of the VZV genomes from the first and second episodes of HZ in each of the five participants indicate that both episodes were caused by the same VZV strain. This is consistent with the extraordinary stability of VZV during the replication phase of varicella and the subsequent establishment of latency in sensory ganglia throughout the body. Our observations also indicate that VZV is stable during the persistence of latency and the subsequent reactivation and replication that results in HZ

Iterative Approximate Consensus in the presence of Byzantine Link Failures

This paper explores the problem of reaching approximate consensus in synchronous point-to-point networks, where each directed link of the underlying communication graph represents a communication channel between a pair of nodes. We adopt the transient Byzantine link failure model [15, 16], where an omniscient adversary controls a subset of the directed communication links, but the nodes are assumed to be fault-free. Recent work has addressed the problem of reaching approximate consen- sus in incomplete graphs with Byzantine nodes using a restricted class of iterative algorithms that maintain only a small amount of memory across iterations [22, 21, 23, 12]. However, to the best of our knowledge, we are the first to consider approximate consensus in the presence of Byzan- tine links. We extend our past work that provided exact characterization of graphs in which the iterative approximate consensus problem in the presence of Byzantine node failures is solvable [22, 21]. In particular, we prove a tight necessary and sufficient condition on the underlying com- munication graph for the existence of iterative approximate consensus algorithms under transient Byzantine link model. The condition answers (part of) the open problem stated in [16].Comment: arXiv admin note: text overlap with arXiv:1202.609

NMR Derived Model of GTPase Effector Domain (GED) Self Association: Relevance to Dynamin Assembly

Self-association of dynamin to form spiral structures around lipidic vesicles during endocytosis is largely mediated by its ‘coiled coil’ GTPase Effector Domain (GED), which, in vitro, self-associates into huge helical assemblies. Residue-level structural characterizations of these assemblies and understanding the process of association have remained a challenge. It is also impossible to get folded monomers in the solution phase. In this context, we have developed here a strategy to probe the self-association of GED by first dissociating the assembly using Dimethyl Sulfoxide (DMSO) and then systematically monitoring the refolding into helix and concomitant re-association using NMR spectroscopy, as DMSO concentration is progressively reduced. The short segment, Arg109 - Met116, acts as the nucleation site for helix formation and self-association. Hydrophobic and complementary charge interactions on the surfaces drive self-association, as the helices elongate in both the directions resulting in an antiparallel stack. A small N-terminal segment remains floppy in the assembly. Following these and other published results on inter-domain interactions, we have proposed a plausible mode of dynamin self assembly

Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data

Background: MicroRNAs (miRNAs) are short, non-coding RNA regulators of protein coding genes. miRNAs play a very important role in diverse biological processes and various diseases. Many algorithms are able to predict miRNA genes and their targets, but their transcription regulation is still under investigation. It is generally believed that intragenic miRNAs (located in introns or exons of protein coding genes) are co-transcribed with their host genes and most intergenic miRNAs transcribed from their own RNA polymerase II (Pol II) promoter. However, the length of the primary transcripts and promoter organization is currently unknown. Methodology: We performed Pol II chromatin immunoprecipitation (ChIP)-chip using a custom array surrounding regions of known miRNA genes. To identify the true core transcription start sites of the miRNA genes we developed a new tool (CPPP). We showed that miRNA genes can be transcribed from promoters located several kilobases away and that their promoters share the same general features as those of protein coding genes. Finally, we found evidence that as many as 26% of the intragenic miRNAs may be transcribed from their own unique promoters. Conclusion: miRNA promoters have similar features to those of protein coding genes, but miRNA transcript organization is more complex. © 2009 Corcoran et al

Chemo- and Thermosensory Responsiveness of Grueneberg Ganglion Neurons Relies on Cyclic Guanosine Monophosphate Signaling Elements

Neurons of the Grueneberg ganglion (GG) in the anterior nasal region of mouse pups respond to cool temperatures and to a small set of odorants. While the thermosensory reactivity appears to be mediated by elements of a cyclic guanosine monophosphate (cGMP) cascade, the molecular mechanisms underlying the odor-induced responses are unclear. Since odor-responsive GG cells are endowed with elements of a cGMP pathway, specifically the transmembrane guanylyl cyclase subtype GC-G and the cyclic nucleotide-gated ion channel CNGA3, the possibility was explored whether these cGMP signaling elements may also be involved in chemosensory GG responses. Experiments with transgenic mice deficient for GC-G or CNGA3 revealed that GG responsiveness to given odorants was significantly diminished in these knockout animals. These findings suggest that a cGMP cascade may be important for both olfactory and thermosensory signaling in the GG. However, in contrast to the thermosensory reactivity, which did not decline over time, the chemosensory response underwent adaptation upon extended stimulation, suggesting that the two transduction processes only partially overlap. Copyright (C) 2011 S. Karger AG, Base

Quantitative assessment of cardiac load-responsiveness during extracorporeal life support: case and rationale

We describe a case of a patient assisted by extracorporeal life support, in which we obtained the dynamic filling index, a measure for venous volume during extracorporeal life support, and used this index to assess cardiac load-responsiveness during acute reloading. While reloading, the obtained findings on cardiac pump function by the dynamic filling index were supported by trans-esophageal echocardiography and standard pressure measurement. This suggests that the dynamic filling index can be used to assess cardiac load-responsiveness during extracorporeal life support

Gilbert Damping in Conducting Ferromagnets II: Model Tests of the Torque-Correlation Formula

We report on a study of Gilbert damping due to particle-hole pair excitations in conducting ferromagnets. We focus on a toy two-band model and on a four-band spherical model which provides an approximate description of ferromagnetic (Ga,Mn)As. These models are sufficiently simple that disorder-ladder-sum vertex corrections to the long-wavelength spin-spin response function can be summed to all orders. An important objective of this study is to assess the reliability of practical approximate expressions which can be combined with electronic structure calculations to estimate Gilbert damping in more complex systems.Comment: 10 pages, 10 figures. Submitted to Phys. Rev.

Solutions of Several Coupled Discrete Models in terms of Lame Polynomials of Arbitrary Order

Coupled discrete models abound in several areas of physics. Here we provide an extensive set of exact quasiperiodic solutions of a number of coupled discrete models in terms of Lam\'e polynomials of arbitrary order. The models discussed are (i) coupled Salerno model, (ii) coupled Ablowitz-Ladik model, (iii) coupled $\phi^4$ model, and (iv) coupled $\phi^6$ model. In all these cases we show that the coefficients of the Lam\'e polynomials are such that the Lam\'e polynomials can be reexpressed in terms of Chebyshev polynomials of the relevant Jacobi elliptic function

Pupil Size in Spider Eyes Is Linked to Post-Ecdysal Lens Growth

In this study we describe a distinctive pigment ring that appears in spider eyes after ecdysis and successively decreases in size in the days thereafter. Although pigment stops in spider eyes are well known, size variability is, to our knowledge, reported here for the first time. Representative species from three families (Ctenidae, Sparassidae and Lycosidae) are investigated and, for one of these species (Cupiennius salei, Ctenidae), the progressive increase in pupil diameter is monitored. In this species the pupil occupies only a fourth of the total projected lens surface after ecdysis and reaches its final size after approximately ten days. MicroCT images suggest that the decrease of the pigment ring is linked to the growth of the corneal lens after ecdysis. The pigment rings might improve vision in the immature eye by shielding light rays that would otherwise enter the eye via peripheral regions of the cornea, beside the growing crystalline lens

Suspected retinopathies in Norwegian optometric practice with emphasis on patients with diabetes: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The scope of optometry differs worldwide. In Norway the vast majority of optometrists perform ophthalmoscopy as part of their routine examinations. The aim of this study was to describe the frequency of <it>suspected </it>retinopathies in patients seen for routine optometric examination and to determine how optometrists deal with these patients.</p> <p>Methods</p> <p>212 optometrists participated in a questionnaire survey and a practice registration during November 2004 – May 2005. In the practice registration, details for 20 consecutive patient encounters were recorded. Data were analysed by chi-square tests and multiple logistic regression.</p> <p>Results</p> <p>All optometrist stated that ocular history taking was an integrated part of their routine examination, while general health and diabetes history were routinely addressed by 59% and 42% of the optometrists, respectively. During the practice registration 4,052 patient encounters were recorded. Ophthalmoscopy was performed in 88% of the patients, of which 2% were dilated fundus examinations. Retinopathy was <it>suspected </it>in 106 patients, of whom 31 did not report a previous history of ocular or systemic disease. Old age (75+), hypertension and diabetes strongly predicted retinopathy with odds ratio (95% CI) of 6.4 (4.2 to 9.9), 3.8 (2.4 to 6.0) and 2.5 (1.4 to 4.7), respectively. Diabetic retinopathy was seen in 10% of diabetic patients and <it>suspected </it>in 0.2% of patients with no established history of diabetes. Retinopathy was not confirmed in 9 out 18 patients with a history of diabetic retinopathy; seven of these had undergone laser treatment. Out of the 106 patients with findings of retinopathy, 28 were referred to an ophthalmologist or a general practitioner (GP), written reports were sent to a GP in 16 cases, ten patients were urged to contact their GP for further follow up, while 52 were considered in need of routine optometric follow up only.</p> <p>Conclusion</p> <p>Optometric practice provides a low threshold setting for detecting cases of ocular disease and retinal manifestations of systemic disease in the population. At present diagnosis of retinopathy in Norwegian optometric practice is unreliable. There are potentials for improving the optometrists' routine examination, their patient management patterns and collaboration routines with medical doctors.</p