The effect of bleach duration and age on the ERG photostress test

Background: The ERG photostress test assesses the recovery of the focal 41 Hz ERG following exposure to a bright light that bleaches a significant proportion of photopigment. The aims of this study were: 1) to compare the repeatability of the ERG photostress test recovery time constant following long and short duration light exposure, and 2) to determine the effect of age on the ERG photostress test recovery time constant. Methods: Focal 41 Hz ERGs were recorded from 23 participants (age range 20–71 years) at 20-second intervals for 5 minutes following either a short-duration (photoflash) or long-duration (equilibrium) light exposure. After a 5-minute wash-out period, the procedure was repeated using the second bleach modality. The time constant of cone recovery was determined by fitting an exponential model to the amplitude recovery data. The whole procedure was repeated on a second occasion. The co-efficient of repeatability (CoR) was calculated for each bleaching technique. The relationship between the time constant of recovery and age was investigated (Pearson’s correlation coefficient). Results: The time constant of recovery following an equilibrium bleach was more repeatable than recovery following a photoflash (CoR = 85s and 184s respectively). Eight trials (from seven participants) failed to show a reduction in amplitude following the photoflash, suggesting that a blink or fixation loss had occurred. All participants were reliably light-adapted by the equilibrium bleach. For the equilibrium bleach data, the time constant of recovery increased with age at a rate of 27 seconds per decade. Conclusions: The equilibrium bleach was more reliable and repeatable than the photoflash. Increasing participant age was shown to result in a lengthening of the recovery time constant, of a magnitude comparable to previously published psychophysical data

Lambs with Scrapie Susceptible Genotypes Have Higher Postnatal Survival

BACKGROUND: Prion protein (PrP) alleles associated with scrapie susceptibility persist in many sheep populations even with high frequencies despite centuries of selection against them. This suggests that scrapie susceptibility alleles have a pleiotropic effect or are associated with fitness or other traits that have been subject to selection. METHODOLOGY/PRINCIPAL FINDINGS: We genotyped all lambs in two scrapie-free Scottish Blackface sheep flocks for polymorphisms at codons 136, 154 and 171 of the PrP gene. We tested potential associations of the PrP genotype with lamb viability at birth and postnatal survival using a complementary log-log link function and a Weibull proportional hazard model, respectively. Here we show there is an association between PrP genotype, as defined by polymorphisms at codons 154 ad 171, and postnatal lamb survival in the absence of scrapie. Sheep carrying the wild-type ARQ allele have higher postnatal survival rates than sheep carrying the more scrapie-resistant alleles (ARR or AHQ). CONCLUSION: The PrP genotypes associated with higher susceptibility to scrapie are associated with improved postnatal survival in the absence of the disease. This association helps to explain the existence, and in many instances the high frequency, of the ARQ allele in sheep populations

GABAA-Mediated Inhibition Modulates Stimulus-Specific Adaptation in the Inferior Colliculus

The ability to detect novel sounds in a complex acoustic context is crucial for survival. Neurons from midbrain through cortical levels adapt to repetitive stimuli, while maintaining responsiveness to rare stimuli, a phenomenon called stimulus-specific adaptation (SSA). The site of origin and mechanism of SSA are currently unknown. We used microiontophoretic application of gabazine to examine the role of GABAA-mediated inhibition in SSA in the inferior colliculus, the midbrain center for auditory processing. We found that gabazine slowed down the process of adaptation to high probability stimuli but did not abolish it, with response magnitude and latency still depending on the probability of the stimulus. Blocking GABAA receptors increased the firing rate to high and low probability stimuli, but did not completely equalize the responses. Together, these findings suggest that GABAA-mediated inhibition acts as a gain control mechanism that enhances SSA by modifying the responsiveness of the neuron

A search for ultrahigh-energy neutrinos associated with astrophysical sources using the third flight of ANITA

The ANtarctic Impulsive Transient Antenna (ANITA) long-duration balloon experiment is sensitive to interactions of ultrahigh-energy (E>1018 eV) neutrinos in the Antarctic ice sheet. The third flight of ANITA, lasting 22 days, began in December 2014. We develop a methodology to search for energetic neutrinos spatially and temporally coincident with potential source classes in ANITA data. This methodology is applied to several source classes: the potential IceCube-identified neutrino sources TXS 0506+056 and NGC 1068, flaring high-energy blazars reported by the Fermi All-Sky Variability Analysis, gamma-ray bursts, and supernovae. Among searches within the five source classes, one candidate was identified as associated with SN 2015D, although not at a statistically significant level. We proceed to place upper limits on the source classes. We further comment on potential application of this methodology to more sensitive future instruments

An analysis of a tau-neutrino hypothesis for the near-horizon cosmic-ray-like events observed by ANITA-IV

We present the results of a simulation of the acceptance of the Antarctic Impulsive Transient Antenna (ANITA) to possible υτ point source fluxes detected via τ-lepton-induced air showers. This investigation is framed around the detection of four upward-going extensive air shower events observed very close to the horizon in ANITA-IV. These four events as well as the overall diffuse and point source exposure to Earth-skimming υτ are also compared against published ultrahigh-energy neutrino limits from the Pierre Auger Observatory. We find that while these four events were detected at sky coordinates close to ANITA’s maximum υτ sensitivity and were not simultaneously visible by Auger, the implied fluence necessary for ANITA to observe these events is in tension with limits set by Auger across a wide range of energies and is additionally in tension with ANITA’s Askaryan in-ice neutrino channel above 1019 eV

Analysis of a tau neutrino origin for the near-horizon air shower events observed by the fourth flight of the Antarctic Impulsive Transient Antenna

We study in detail the sensitivity of the Antarctic Impulsive Transient Antenna (ANITA) to possible Formula Presented point source fluxes detected via Formula Presented-lepton-induced air showers. This investigation is framed around the observation of four upward-going extensive air shower events very close to the horizon seen in ANITA-IV. We find that these four upgoing events are not observationally inconsistent with Formula Presented-induced EASs from Earth-skimming Formula Presented both in their spectral properties as well as in their observed locations on the sky. These four events as well as the overall diffuse and point source exposure to Earth-skimming Formula Presented are also compared against published ultrahigh-energy neutrino limits from the Pierre Auger Observatory. While none of these four events occurred at sky locations simultaneously visible by Auger, the implied fluence necessary for ANITA to observe these events is in strong tension with limits set by Auger across a wide range of energies and is additionally in tension with ANITA’s Askaryan in-ice neutrino channel above Formula Presented. We conclude by discussing some of the technical challenges with simulating and analyzing these near horizon events and the potential for future observatories to observe similar events

Characteristics and Spatial Distribution of Structural Features in Age-Related Macular Degeneration: A MACUSTAR Study Report

Purpose: To report the prevalence and topographic distribution of structural characteristics in study participants with age-related macular degeneration (AMD) and controls in the cross-sectional study part of the MACUSTAR study (ClinicalTrials.gov Identifier: NCT03349801). Design: European, multicenter cohort study. Subjects: Overall, 301 eyes of 301 subjects with early (n = 34), intermediate (n = 168), and late AMD (n = 43), as well as eyes without any AMD features (n = 56). Methods: In study eyes with intermediate AMD (iAMD), the presence of structural AMD biomarkers, including pigmentary abnormalities (PAs), pigment epithelium detachment (PED), refractile deposits, reticular pseudodrusen (RPD), hyperreflective foci (HRF), incomplete/complete retinal pigment epithelium (RPE), and outer retinal atrophy (i/cRORA), and quiescent choroidal neovascularization (qCNV) was systematically determined in the prospectively acquired multimodal retinal imaging cross-sectional data set of MACUSTAR. Retinal layer thicknesses and the RPE drusen complex (RPEDC) volume were determined for the total study cohort in spectral-domain (SD) OCT imaging using a deep-learning–based algorithm. Main Outcome Measures: Prevalence and topographic distribution of structural iAMD features. Results: A total of 301 study eyes of 301 subjects with a mean (± standard deviation) age of 71.2 ± 7.20 years (63.1% women) were included. Besides large drusen, the most prevalent structural feature in iAMD study eyes were PA (57.1%), followed by HRF (51.8%) and RPD (22.0%). Pigment epithelium detachment lesions were observed in 4.8%, vitelliform lesions in 4.2%, refractile deposits in 3.0%, and qCNV in 2.4%. Direct precursor lesions for manifest retinal atrophy were detected in 10.7% (iRORA) and 4.2% (cRORA) in iAMD eyes. Overall, the highest RPEDC volume with a median of 98.92 × 10−4 mm³ was found in iAMD study eyes. Spatial analysis demonstrated a predominant distribution of RPD in the superior and temporal subfields at a foveal eccentricity of 1.5 to 2 mm, whereas HRF and large drusen had a distinct topographic distribution involving the foveal center. Conclusions: Detailed knowledge of the prevalence and distribution of structural iAMD biomarkers is vital to identify reliable outcome measure for disease progression. Longitudinal analyses are needed to evaluate their prognostic value for conversion to advanced disease stages. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references

Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains

Ruiz JC, D'Afonseca V, Silva A, et al. Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains. PLoS ONE. 2011;6(4): e18551.Background: Corynebacterium pseudotuberculosis, a Gram-positive, facultative intracellular pathogen, is the etiologic agent of the disease known as caseous lymphadenitis (CL). CL mainly affects small ruminants, such as goats and sheep; it also causes infections in humans, though rarely. This species is distributed worldwide, but it has the most serious economic impact in Oceania, Africa and South America. Although C. pseudotuberculosis causes major health and productivity problems for livestock, little is known about the molecular basis of its pathogenicity. Methodology and Findings: We characterized two C. pseudotuberculosis genomes (Cp1002, isolated from goats; and CpC231, isolated from sheep). Analysis of the predicted genomes showed high similarity in genomic architecture, gene content and genetic order. When C. pseudotuberculosis was compared with other Corynebacterium species, it became evident that this pathogenic species has lost numerous genes, resulting in one of the smallest genomes in the genus. Other differences that could be part of the adaptation to pathogenicity include a lower GC content, of about 52%, and a reduced gene repertoire. The C. pseudotuberculosis genome also includes seven putative pathogenicity islands, which contain several classical virulence factors, including genes for fimbrial subunits, adhesion factors, iron uptake and secreted toxins. Additionally, all of the virulence factors in the islands have characteristics that indicate horizontal transfer. Conclusions: These particular genome characteristics of C. pseudotuberculosis, as well as its acquired virulence factors in pathogenicity islands, provide evidence of its lifestyle and of the pathogenicity pathways used by this pathogen in the infection process. All genomes cited in this study are available in the NCBI Genbank database (http://www.ncbi.nlm.nih.gov/genbank/) under accession numbers CP001809 and CP001829