Inhibition of Vaginal Lactobacilli by a Bacteriocin-Like Inhibitor Produced by Enterococcus faecium 62-6: Potential Significance for Bacterial Vaginosis

Objective: Bacterial vaginosis (BV) is characterized by a shift in vaginal tract ecology, which includes a decrease in the concentration and/or prevalence of facultative lactobacilli. Currently, mechanisms which could account for the disappearance of lactobacilli are not well understood. The objective of this study was to determine whether vaginal streptococci/enterococci can produce bacteriocin-like inhibitors antagonistic to vaginal lactobacilli. Methods: Seventy strains of vaginal streptococci or enterococci were tested for antagonistic activities against vaginal lactobacilli using the deferred antagonism technique. Results: One strain, Enterococcus faecium 62-6, which strongly inhibited growth of lactobacilli was selected for further characterization. The spectrum of inhibitory activity of strain 62-6 included Gram-positive organisms from the vaginal environment, although native lactobacilli from the same host were resistant to inhibitor action. Following growth inMRSbroth the strain 62-6 inhibitor was shown to be heat- (100℃, 30 minutes), cold- (4℃, less than 114 days) and pH- (4–7) stable. The sensitivity of inhibitor-containing supernatants to pepsin and α-chymotrypsin suggested an essential proteinaceous component. The inhibitor was sensitive to lipase but resistant to lysozyme. Dialysis of inhibitor-containing culture supernatants suggested a molecular mass greater than 12 000 Da. All physicochemical properties were consistent with its classification as a bacteriocin-like inhibitor. Kinetic assays demonstrated a sharp onset of inhibitor production coinciding with a concentration of 62-6 of 10(7) cfu/ml, suggesting that production may be regulated by quorum sensing. Conclusions: These results may have clinical significance as a novel mechanism to account for the decline of vaginal Lactobacillus populations and contribute to both the establishment and recurrence of BV

Extracting the Number of Short Range Correlated Nucleon Pairs from Inclusive Electron Scattering Data

The extraction of the relative abundances of short-range correlated (SRC) nucleon pairs from inclusive electron scattering is studied using the generalized contact formalism (GCF) with several nuclear interaction models. GCF calculations can reproduce the observed scaling of the cross-section ratios for nuclei relative to deuterium at high xB and large Q2, a2 = (σA/A)/(σd/2). In the nonrelativistic instant-form formulation, the calculation is very sensitive to the model parameters and only reproduces the data using parameters that are inconsistent with ab initio many-body calculations. Using a light-cone GCF formulation significantly decreases this sensitivity and improves the agreement with ab initio calculations. The ratio of similar mass isotopes, such as 40Ca and 48Ca, should be sensitive to the nuclear asymmetry dependence of SRCs, but is found to also be sensitive to low-energy nuclear structure. Thus the empirical association of SRC pair abundances with the measured a2 values is only accurate to about 20%. Improving this will require cross-section calculations that reproduce the data while properly accounting for both nuclear structure and relativistic effects

Extracing the number of short-range corerlated nucleon pairs from inclusive electron scattering data

The extraction of the relative abundances of short-range correlated (SRC) nucleon pairs from inclusive electron scattering is studied using the generalized contact formalism (GCF) with several nuclear interaction models. GCF calculations can reproduce the observed scaling of the cross-section ratios for nuclei relative to deuterium at high-$x_B$ and large-$Q^2$, $a_2=(\sigma_A/A)/(\sigma_d/2)$. In the non-relativistic instant-form formulation, the calculation is very sensitive to the model parameters and only reproduces the data using parameters that are inconsistent with ab-initio many-body calculations. Using a light-cone GCF formulation significantly decreases this sensitivity and improves the agreement with ab-initio calculations. The ratio of similar mass isotopes, such as $^{40}$Ca and $^{48}$Ca, should be sensitive to the nuclear asymmetry dependence of SRCs, but is found to also be sensitive to low-energy nuclear structure. Thus the empirical association of SRC pair abundances with the measured $a_2$ values is only accurate to about $20\%$. Improving this will require cross-section calculations that reproduce the data while properly accounting for both nuclear structure and relativistic effects.Comment: Accepted for publication in Phys. Rev. C (Lett). 6 pages, 4 figures, and online supplementary material

Laser Calibration System for Time of Flight Scintillator Arrays

A laser calibration system was developed for monitoring and calibrating time of flight (TOF) scintillating detector arrays. The system includes setups for both small- and large-scale scintillator arrays. Following test-bench characterization, the laser system was recently commissioned in experimental Hall B at the Thomas Jefferson National Accelerator Facility for use on the new Backward Angle Neutron Detector (BAND) scintillator array. The system successfully provided time walk corrections, absolute time calibration, and TOF drift correction for the scintillators in BAND. This showcases the general applicability of the system for use on high-precision TOF detectors.Comment: 11 pages, 11 figure

Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic Hepatitis C Virus Infection.

The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens. Notably, we find an exceptional level of heterogeneity in the molecular evolution of HCV, both within and among infected individuals. Furthermore, these patterns are associated with the long-term maintenance of viral lineages within patients, which fluctuate in relative frequency in peripheral blood. Together, our findings demonstrate that HCV replication behavior is complex and likely comprises multiple viral subpopulations with distinct evolutionary dynamics. The presence of a structured viral population can explain apparent paradoxes in chronic HCV infection, such as rapid fluctuations in viral diversity and the reappearance of viral strains years after their initial detection.status: publishe

Direct Observation of Proton-Neutron Short-Range Correlation Dominance in Heavy Nuclei

We measured the triple coincidence A(e,e′n p) and A(e,e′ p p) reactions on carbon, aluminum, iron, and lead targets at Q2 \u3e1.5  (GeV/c)2, xB \u3e 1.1 and missing momentum \u3e400  MeV/c. This was the first direct measurement of both proton-proton (pp) and neutron-proton (np) short-range correlated (SRC) pair knockout from heavy asymmetric nuclei. For all measured nuclei, the average proton-proton (pp) to neutron-proton (np) reduced cross-section ratio is about 6%, in agreement with previous indirect measurements. Correcting for single-charge exchange effects decreased the SRC pairs ratio to ∼3%, which is lower than previous results. Comparisons to theoretical generalized contact formalism (GCF) cross-section calculations show good agreement using both phenomenological and chiral nucleon-nucleon potentials, favoring a lower pp to np pair ratio. The ability of the GCF calculation to describe the experimental data using either phenomenological or chiral potentials suggests possible reduction of scale and scheme dependence in cross-section ratios. Our results also support the high-resolution description of high-momentum states being predominantly due to nucleons in SRC pairs

The mode and tempo of hepatitis C virus evolution within and among hosts

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) is a rapidly-evolving RNA virus that establishes chronic infections in humans. Despite the virus' public health importance and a wealth of sequence data, basic aspects of HCV molecular evolution remain poorly understood. Here we investigate three sets of whole HCV genomes in order to directly compare the evolution of whole HCV genomes at different biological levels: within- and among-hosts. We use a powerful Bayesian inference framework that incorporates both among-lineage rate heterogeneity and phylogenetic uncertainty into estimates of evolutionary parameters.</p> <p>Results</p> <p>Most of the HCV genome evolves at ~0.001 substitutions/site/year, a rate typical of RNA viruses. The antigenically-important <it>E1/E2 </it>genome region evolves particularly quickly, with correspondingly high rates of positive selection, as inferred using two related measures. Crucially, in this region an exceptionally higher rate was observed for within-host evolution compared to among-host evolution. Conversely, higher rates of evolution were seen among-hosts for functionally relevant parts of the <it>NS5A </it>gene. There was also evidence for slightly higher evolutionary rate for HCV subtype 1a compared to subtype 1b.</p> <p>Conclusions</p> <p>Using new statistical methods and comparable whole genome datasets we have quantified, for the first time, the variation in HCV evolutionary dynamics at different scales of organisation. This confirms that differences in molecular evolution between biological scales are not restricted to HIV and may represent a common feature of chronic RNA viral infection. We conclude that the elevated rate observed in the <it>E1/E2 </it>region during within-host evolution more likely results from the reversion of host-specific adaptations (resulting in slower long-term among-host evolution) than from the preferential transmission of slowly-evolving lineages.</p

Molecular evolution, diversity and adaptation of H7N9 viruses in China during 2013-2017

The substantial increase in prevalence and emergence of antigenically divergent or highly pathogenic influenza A(H7N9) viruses during 2016–17 raises concerns about the epizootic potential of these viruses. We investigated the evolution and adaptation of H7N9 viruses by analyzing available data and newly generated virus sequences isolated in Guangdong Province, China, during 2015–2017. Phylogenetic analyses showed that circulating H7N9 viruses belong to distinct lineages with differing spatial distributions. Hemagglutination inhibition assays performed on serum samples from patients infected with these viruses identified 3 antigenic clusters for 16 strains of different virus lineages. We used ancestral sequence reconstruction to identify parallel amino acid changes on multiple separate lineages. We inferred that mutations in hemagglutinin occur primarily at sites involved in receptor recognition or antigenicity. Our results indicate that highly pathogenic strains likely emerged from viruses circulating in eastern Guangdong Province during March 2016 and are associated with a high rate of adaptive molecular evolution