BV equivalence with boundary.

An extension of the notion of classical equivalence of equivalence in the Batalin-Vilkovisky (BV) and Batalin-Fradkin-Vilkovisky (BFV) frameworks for local Lagrangian field theory on manifolds possibly with boundary is discussed. Equivalence is phrased in both a strict and a lax sense, distinguished by the compatibility between the BV data for a field theory and its boundary BFV data, necessary for quantisation. In this context, the first- and second-order formulations of nonabelian Yang-Mills and of classical mechanics on curved backgrounds, all of which admit a strict BV-BFV description, are shown to be pairwise equivalent as strict BV-BFV theories. This in particular implies that their BV complexes are quasi-isomorphic. Furthermore, Jacobi theory and one-dimensional gravity coupled with scalar matter are compared as classically equivalent reparametrisation-invariant versions of classical mechanics, but such that only the latter admits a strict BV-BFV formulation. They are shown to be equivalent as lax BV-BFV theories and to have isomorphic BV cohomologies. This shows that strict BV-BFV equivalence is a strictly finer notion of equivalence of theories.

Functional characterization of the bovine foamy virus miRNA expression cassette and its dumbbell-shaped pri-miRNA.

Foamy viruses are unconventional and complex retroviruses distinct from the other members of the Retroviridae family. Currently, no disease has been firmly linked to persistent foamy virus infection of their cognate host including simians, bovines, felines, and equines or upon zoonotic transmission of different simian foamy viruses to humans. Bovine and simian foamy viruses have been recently shown to encode a RNA polymerase-III-driven micro RNA cluster which likely modulates and regulates host-virus interactions at different levels. Using sub-genomic bovine foamy virus micro RNA expression plasmids and dual luciferase reporter assays as readout, the requirements for expression and processing of the bovine foamy virus micro RNAs have been analyzed. Here, we report that the minimal BFV micro RNA cassette is significantly weaker than a U6 promoter-based construct and strongly suppressed by flanking sequences. The primary micro RNA sequence can be manipulated and chimerized as long as the dumbbell-like folding of the primary micro RNA is maintained. Since more subtle changes are associated with reduced functionality, the overall structure and shape, but possibly individual elements and residues also, are important for the expression and processing of the bovine foamy virus micro RNAs.

The effect of bovine BST2A1 on the release and cell-to-cell transmission of retroviruses.

BACKGROUND: Human BST2 (hBST2, also called Tetherin) is a host restriction factor that blocks the release of various enveloped viruses. BST2s from different mammals also possess antiviral activity. Bovine BST2s (bBST2s), bBST2A1 and bBST2A2, reduce production of cell-free bovine leukemia virus (BLV) and vesicular stomatitis virus (VSV). However, the effect of bBST2 on other retroviruses remains unstudied. RESULTS: Here, we studied the antiviral activity of wildtype and mutant bBST2A1 proteins on retroviruses including human immunodeficiency virus type 1 (HIV-1), prototypic foamy virus (PFV), bovine foamy virus (BFV) and bovine immunodeficiency virus (BIV). The results showed that wildtype bBST2A1 suppressed the release of HIV-1, PFV and BFV. We also generated bBST2A1 mutants, and found that GPI anchor and dimerization, but not glycosylation, are essential for antiviral activity of bBST2A1. Moreover, unlike hBST2, bBST2A1 displayed no inhibitory effect on cell-to-cell transmission of PFV, BFV and BIV. CONCLUSIONS: Our data suggested that bBST2A1 inhibited retrovirus release, however, had no effect on cell-to-cell transmission of retroviruses.

Dataset of middle cerebral artery blood flow stability in response to high-definition transcranial electrical stimulation.

This supplementary dataset is supportive of the randomized sham-controlled, double-blind, crossover clinical trial investigating polarity- and intensity-dependent effects of high-definition transcranial electrical stimulation (HD-tDCS) applied over the right temporo-parietal junction on mean middle cerebral artery blood flow velocity (MCA-BFv) bilaterally. Data of eleven healthy right-handed adults (6 women, 5 men; mean age 31 ± 5.6 years old) were analyzed for MCA-BFv, assessed using transcranial doppler ultrasound on the stimulated and the contralateral hemisphere concomitantly, during and after 3 blocks of 2 min HD-tDCS at 1, 2, and 3 mA. Participants received three electrical stimulation conditions (anode center, cathode center, and sham) randomly ordered across different days. The collected data is publicly available at Mendeley Data. This article and the data will inform future related investigations and safety analysis of transcranial non-invasive brain stimulation.

Molecular characterization of bovine foamy virus and its association with bovine leukemia virus infection in Vietnamese cattle.

The detection of bovine foamy virus (BFV) in Vietnamese cattle was performed using conventional PCR targeting pol and gag genes. Out of 243 tested samples, ten (4.1%) and eight (3.3%) samples were positive for BFV gag and pol DNA, respectively. The prevalence of bovine leukemia virus (BLV) estimated by detection of proviral DNA using nested PCR targeting env gene was 26.7% (65/243). The results of nucleotide sequence alignment and the phylogenetic analysis suggested that Vietnamese BFV strains showed high homology to isolates belonging to either European or non-European clades. There was no significant correlation between BLV and BFV. This study provides information regarding BFV infection and confirms the existence of two BFV clades among Vietnamese cattle for the first time.

Infection with Foamy Virus in Wild Ruminants-Evidence for a New Virus Reservoir?

Foamy viruses (FVs) are widely distributed and infect many animal species including non-human primates, horses, cattle, and cats. Several reports also suggest that other species can be FV hosts. Since most of such studies involved livestock or companion animals, we aimed to test blood samples from wild ruminants for the presence of FV-specific antibodies and, subsequently, genetic material. Out of 269 serum samples tested by ELISA with the bovine foamy virus (BFV) Gag and Bet antigens, 23 sera showed increased reactivity to at least one of them. High reactive sera represented 30% of bison samples and 7.5% of deer specimens. Eleven of the ELISA-positives were also strongly positive in immunoblot analyses. The peripheral blood DNA of seroreactive animals was tested by semi-nested PCR. The specific 275 bp fragment of the pol gene was amplified only in one sample collected from a red deer and the analysis of its sequence showed the highest homology for European BFV isolates. Such results may suggest the existence of a new FV reservoir in bison as well as in deer populations. Whether the origin of such infections stems from a new FV or is the result of BFV inter-species transmission remains to be clarified.

Bovine Foamy Virus: Shared and Unique Molecular Features In Vitro and In Vivo.

The retroviral subfamily of Spumaretrovirinae consists of five genera of foamy (spuma) viruses (FVs) that are endemic in some mammalian hosts [1]. Closely related species may be susceptible to the same or highly related FVs. FVs are not known to induce overt disease and thus do not pose medical problems to humans and livestock or companion animals. A robust lab animal model is not available or is a lab animal a natural host of a FV. Due to this, research is limited and often focused on the simian FVs with their well-established zoonotic potential. The authors of this review and their groups have conducted several studies on bovine FV (BFV) in the past with the intention of (i) exploring the risk of zoonotic infection via beef and raw cattle products, (ii) studying a co-factorial role of BFV in different cattle diseases with unclear etiology, (iii) exploring unique features of FV molecular biology and replication strategies in non-simian FVs, and (iv) conducting animal studies and functional virology in BFV-infected calves as a model for corresponding studies in primates or small lab animals. These studies gained new insights into FV-host interactions, mechanisms of gene expression, and transcriptional regulation, including miRNA biology, host-directed restriction of FV replication, spread and distribution in the infected animal, and at the population level. The current review attempts to summarize these findings in BFV and tries to connect them to findings from other FVs.

Assessment of tissue permeability by early CT perfusion as a surrogate parameter for early brain injury after subarachnoid hemorrhage.

OBJECTIVE: The severity of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) correlates with delayed cerebral ischemia (DCI) and outcome. A disruption of the blood-brain barrier is part of EBI pathophysiology. The aim of this study was to assess tissue permeability (PMB) by CT perfusion (CTP) in the acute phase after aSAH and its impact on DCI and outcome. METHODS: CTP was performed on day 3 after aSAH. Qualitative and quantitative analyses of all CTP parameters, including PMB, were performed. The areas with increased PMB were documented. The value of an early PMB increase as a predictor of DCI and outcome according to the modified Rankin Scale (mRS) grade 3 to 24 months after aSAH was assessed. Possible associations of increased PMB with the Subarachnoid Hemorrhage Early Brain Edema Score (SEBES) and with early perfusion deficits, as radiographic EBI markers, were evaluated. RESULTS: A total of 69 patients were enrolled in the study. An increased PMB on early CTP was detected in 10.1% (7/69) of all patients. A favorable outcome (mRS grade ≤ 2) occurred in 40.6% (28/69) of all patients. DCI was detected in 25% (17/69) of all patients. An increased PMB was a predictor of DCI (logistic regression, p = 0.03) but not of outcome (logistic regression, p = 0.40). The detection of increased PMB predicted DCI with a sensitivity of 25%, a specificity of 94%, a positive predictive value of 57%, and a negative predictive value of 79% (chi-square test p = 0.03). Early perfusion deficits were seen in 68.1% (47/69) of the patients, a finding that correlated with DCI (p = 0.005) but not with the outcome. No correlation was found between the SEBES and increased PMB. CONCLUSIONS: Changes in PMB can be detected by early CTP after aSAH, which correlates with DCI. Future studies are needed to evaluate the time course of PMB changes and their interaction with therapeutic measures.

Assessment of blood flow velocities and venous pressures using a dual-sensor guidewire in symptomatic dural sinus stenoses.

Lateral venous sinus stenoses have been associated with idiopathic intracranial hypertension and venous pulsatile tinnitus. Venous pressure measurement is traditionally performed to assess the indications for stenting in patients with idiopathic intracranial hypertension. However, its reliability has recently been questioned by many authors. The dual-sensor guidewire was first developed for advanced physiological assessment of fractional and coronary flow reserves in coronary artery stenoses. It allows measurement of both venous pressure and blood flow velocities. The authors used this device in 14 consecutively treated patients to explore for symptomatic lateral sinus stenosis. They found that venous blood flow was significantly accelerated inside the stenotic lesion. This acceleration, as well as the pulsatile tinnitus, resolved in all patients following stent placement. According to the authors' results, this guidewire can be helpful for establishing an indication for stenting in patients with pulsatile tinnitus and idiopathic intracranial hypertension.

Assessment of intracranial venous blood flow after subarachnoid hemorrhage: a new approach to diagnose vasospasm with transcranial color-coded duplex sonography.

OBJECTIVETranscranial color-coded duplex sonography (TCCS) is a reliable tool that is used to assess vasospasm in the M1 segment of the middle cerebral artery (MCA) after subarachnoid hemorrhage (SAH). A distinct increase in blood flow velocity (BFV) is the principal criterion for vasospasm. The MCA/internal carotid artery (ICA) index (Lindegaard Index) is also widely used to distinguish between vasospasm and cerebral hyperperfusion. However, extracranial ultrasonography assessment of the neck vessels might be difficult in an intensive care unit. Therefore, the authors evaluated whether the relationship of intracranial arterial to venous BFV might indicate vasospasm with similar or even better accuracy.METHODSPatients who presented between 2008 and 2015 with aneurysmal SAH were prospectively enrolled in the study. Digital subtraction angiography (DSA) and TCCS were performed within 24 hours of each other to assess vasospasm 8-10 days after SAH. The following different TCCS parameters were analyzed to assess vasospasm in the MCA and were compared with the gold-standard DSA parameters: 1) mean time-averaged maximum BFV (Vmean) of the MCA, 2) peak systolic velocity (PSV) of the MCA, 3) the Lindegaard Index using Vmean as well as PSV, and 4) a new arteriovenous index (AVI) between the MCA and the basal vein of Rosenthal using Vmean and PSV. The best cutoff values for these parameters to distinguish vasospasm from normal perfusion or hyperperfusion were calculated using receiver operating characteristic curve analysis. Sensitivity, specificity, positive predictive value, and negative predictive value as well as the overall accuracy for each cutoff value were analyzed.RESULTSA total of 102 patients (mean age 52 ± 12 years) were evaluated. Bilateral MCA assessment by TCCS was successful in all patients. In 6 cases (3%), the BFV of the basal vein of Rosenthal could not be analyzed. The AVI could not be calculated in 50 of 204 cases (25%) because the insonation quality was very low in one of the ICAs. An AVI > 10 for Vmean and an AVI > 12 for systolic velocity provided the highest accuracies of 87% and 86%, respectively. Regarding the Lindegaard Index, the accuracy was highest using a threshold of > 3 for the mean BFV (84%) as well as systolic BFV (80%). BFVs in the MCA of ≥ 120 cm/sec (Vmean) and ≥ 200 cm/sec (PSV) predicted vasospasm with accuracies of 84% and 83%, respectively. A combined analysis of the MCA BFV and the AVI led to a slight increase in specificity (Vmean, 94%; PSV, 93%) and positive predictive value (Vmean, 88%; PSV 86%) without further improvement in accuracy (Vmean, 88%; PSV, 84%).CONCLUSIONSThe intracranial AVI is a reliable parameter that can be used to assess vasospasm after SAH. Its reliability for differentiating vasospasm and hyperperfusion is slightly higher than that for the established Lindegaard Index, and this method has the additional advantage of a remarkably lower failure rate.

Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage.

OBJECT This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI). METHODS Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)-measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated. RESULTS Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p < 0.0001). A repeated CTP was performed in 8 patients with a TCD-measured BFV increase > 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI. CONCLUSIONS Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD-measured BFV increase or persisting coma, do not contribute to information gain.

Enhanced arbovirus surveillance with deep sequencing: Identification of novel rhabdoviruses and bunyaviruses in Australian mosquitoes.

Viral metagenomics characterizes known and identifies unknown viruses based on sequence similarities to any previously sequenced viral genomes. A metagenomics approach was used to identify virus sequences in Australian mosquitoes causing cytopathic effects in inoculated mammalian cell cultures. Sequence comparisons revealed strains of Liao Ning virus (Reovirus, Seadornavirus), previously detected only in China, livestock-infecting Stretch Lagoon virus (Reovirus, Orbivirus), two novel dimarhabdoviruses, named Beaumont and North Creek viruses, and two novel orthobunyaviruses, named Murrumbidgee and Salt Ash viruses. The novel virus proteomes diverged by ≥ 50% relative to their closest previously genetically characterized viral relatives. Deep sequencing also generated genomes of Warrego and Wallal viruses, orbiviruses linked to kangaroo blindness, whose genomes had not been fully characterized. This study highlights viral metagenomics in concert with traditional arbovirus surveillance to characterize known and new arboviruses in field-collected mosquitoes. Follow-up epidemiological studies are required to determine whether the novel viruses infect humans.