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Background. Elevated plasma and urine endothelin-1 (ET-1) levels have been reported in renal failure and may be involved in renal disease progression. We investigated whether these changes are related to increased vascular and renal ET-1 production in the pole resection remnant kidney model of chronic renal failure in the rat. [ABSTRACT FROM PUBLISHER]

The first experiment investigated the effects of mild to moderate sensorineural hearing impairment on temporal analysis for noise stimuli of varying bandwidth. Tasks of temporal gap detection, amplitude modulation (AM) detection, and AM discrimination were examined. Relatively high levels of stimulation were used in order to reduce the possibility that the results of the listeners with hearing impairment would be influenced strongly by audibility. A general summary of results was that there was relatively great interlistener variation among the listeners with hearing impairment, with most listeners showing normal performance and some showing degraded performance, regardless of the bandwidth of the stimulus carrying the temporal information. A second experiment investigated the hypothesis that listeners with sensorineural hearing impairment might have poor gap detection due to loudness recruitment. Here, gap markers were presented at levels where loudness growth was steeper for the listeners with hearing impairment than for the listeners with normal hearing. Although gap detection was sometimes poorer in listeners with hearing impairment than in listeners with normal hearing, there was no clear relation between gap detection performance and loudness recruitment in listeners with mild to moderate sensorineural hearing impairment. [ABSTRACT FROM AUTHOR]

The first aim of this study was to obtain a more detailed picture of the effect of masker bandwidth (20 Hz to 1000 Hz bandwidth) on the masking level difference (MLD) for a 500-Hz signal as a function of listener age. The results of the pure-tone signal experiment showed that the MLDs of older children differed from adults only for the narrowest masker bandwidth. In contrast, children younger than about 7 years of age tended to have smaller MLDs than adults at all but the widest masker bandwidth must be for MLDs of adult magnitude to be observed. One interpretation of this effect is that younger listeners require relatively great spectral dissimilarity (and, therefore perceptual dissimilarity) between the signal and masker in order to obtain MLDs of adult magnitude. The second aim of this study was to test this possibility by determining the MLD for noise signals in cases where the signal and masker bandwidths were the same. The results of this experiment showed that the MLDs of children were as large as those of adults when the signal/masker bandwidth was 320 Hz, but were smaller than those of adults when the signal/masker bandwidth was 20 Hz. This indicates that the factor limiting the MLD for narrowband noise in children is related more to the masker bandwidth than to the perceptual similarity between the signal and the masker. [ABSTRACT FROM AUTHOR]

We announce the complete genomes of Klebsiella phages ValerieMcCarty03 and ValerieMcCarty04 isolated from wastewater treatment plant samples that infect a multidrug-resistant Klebsiella oxytoca clinical isolate. These phages belong to the T4-like cluster and fall within the Jiaodavirus genus.

This announcement contains the whole genome sequences of five Ackermannviridae that infect members of the Enterobacteriaceae family of bacteria. Four of the five phages were isolated using Salmonella enterica serovar Typhimurium as a bacterial host: AR2819, Sajous1, SilasIsHot, and FrontPhageNews. ChubbyThor was isolated using Shigella boydii ., Competing Interests: The authors declare no conflict of interest.

Enterobacteriaceae is a large family of Gram-negative bacteria composed of many pathogens, including Salmonella and Shigella . Here, we characterize six bacteriophages that infect Enterobacteriaceae, which were isolated from wastewater plants in the Wasatch front (Utah, United States). These phages are highly similar to the Kuttervirus vB_SenM_Vi01 (Vi01), which was isolated using wastewater from Kiel, Germany. The phages vary little in genome size and are between 157 kb and 164 kb, which is consistent with the sizes of other phages in the Vi01-like phage family. These six phages were characterized through genomic and proteomic comparison, mass spectrometry, and both laboratory and clinical host range studies. While their proteomes are largely unstudied, mass spectrometry analysis confirmed the production of five hypothetical proteins, several of which unveiled a potential operon that suggests a ferritin-mediated entry system on the Vi01-like phage family tail. However, no dependence on this pathway was observed for the single host tested herein. While unable to infect every genus of Enterobacteriaceae tested, these phages are extraordinarily broad ranged, with several demonstrating the ability to infect Salmonella enterica and Citrobacter freundii strains with generally high efficiency, as well as several clinical Salmonella enterica isolates, most likely due to their multiple tail fibers.

The rapid evolution of SARS-CoV-2 has fueled its global proliferation since its discovery in 2019, with several notable variants having been responsible for increases in cases of coronavirus disease 2019 (COVID-19). Analyses of codon bias and usage in these variants between phylogenetic clades or lineages may grant insights into the evolution of SARS-CoV-2 and identify target codons indicative of evolutionary or mutative trends that may prove useful in tracking or defending oneself against emerging strains. We processed a cohort of 120 SARS-CoV-2 genome sequences through a statistical and bioinformatic pipeline to identify codons presenting evidence of selective pressure as well as codon coevolution. We report the identification of two codon sites in the orf8 and N genes demonstrating such evidence with real-world impacts on pathogenicity and transmissivity.

Bacillus anthracis, classified as a Tier 1 Select Agent by the Centers for Disease Control and Prevention (CDC), is the causative agent of anthrax in both humans and livestock. Herein, we report the full genome sequences of 13 bacteriophages that infect B. anthracis Sterne. These phages are grouped into four clusters and are similar to previously described Bacillus phages., Competing Interests: The authors declare no conflict of interest.

Importance: This study reports the results of the largest analysis of genome sequences from phages that infect the Alphaproteobacteria class of bacterial hosts. We analyzed over 100 whole genome sequences of phages to construct dotplots, categorize them into genetically distinct clusters, generate a bootstrapped phylogenetic tree, compute protein orthologs, and predict packaging strategies. We determined that the phage sequences primarily cluster by the bacterial host family, phage morphotype, and genome size. We expect that the findings reported in this seminal study will facilitate future analyses that will improve our knowledge of the phages that infect these hosts., Competing Interests: The authors declare no conflict of interest.

Receptor-binding proteins (RBPs) allow phages to dock onto their host and initiate infection through the recognition of proteinaceous or saccharidic receptors located on the cell surface. FhuA is the ferrichrome hydroxamate transporter in Escherichia coli and serves as a receptor for the well-characterized phages T1, T5, and phi80. To further characterize how other FhuA-dependent phages attach to FhuA, we isolated and published the genomes of three new FhuA-dependent coliphages: JLBYU37, JLBYU41, and JLBYU60. We identified the egions of FhuA involved in phage attachment by testing the effect of mutant fhuA alleles containing single-loop deletions of extracellular loops (L3, L4, L5, L8, L10, and L11) on phage infectivity. Deletion of loop 8 resulted in complete resistance to SO1-like phages JLBYU37 and JLBYU60 and the previously isolated vB_EcoD_Teewinot phage, but no single-loop deletions significantly altered the infection of T1-like JLBYU41. Additionally, lipopolysaccharide (LPS) truncation coupled with the L5 mutant significantly impaired the infectivity of JLBYU37 and JLBYU60. Moreover, significant reductions in the infectivity of JLBYU41 were observed upon LPS truncation in the L8 mutant strain. Analysis of the evolutionary relationships among FhuA-dependent phage RBPs highlights the conservation of L8 dependence in JLBYU37, JLBYU60, Teewinot, T5, and phi80, but also showcases how positive selective pressure and/or homologous recombination also selected for L4 dependence in T1 and even the lack of complete loop dependence in JLBYU41. IMPORTANCE Phage attachment is the first step of phage infection and plays a role in governing host specificity. Characterizing the interactions taking place between phage tail fibers and bacterial receptors that better equip bacteria to survive within the human body may provide insights to aid the development of phage therapeutics., Competing Interests: The authors declare no conflict of interest.

We recently discovered that some bacteriophages establish a nucleus-like replication compartment (phage nucleus), but the core genes that define nucleus-based phage replication and their phylogenetic distribution were still to be determined. Here, we show that phages encoding the major phage nucleus protein chimallin share 72 conserved genes encoded within seven gene blocks. Of these, 21 core genes are unique to nucleus-forming phage, and all but one of these genes encode proteins of unknown function. We propose that these phages comprise a novel viral family we term Chimalliviridae. Fluorescence microscopy and cryoelectron tomography studies of Erwinia phage vB_EamM_RAY confirm that many of the key steps of nucleus-based replication are conserved among diverse chimalliviruses and reveal variations on this replication mechanism. This work expands our understanding of phage nucleus and PhuZ spindle diversity and function, providing a roadmap for identifying key mechanisms underlying nucleus-based phage replication., Competing Interests: Declaration of interests K.P. and J.P. have an equity interest in Linnaeus Bioscience Incorporated and receive income. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict-of-interest policies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Tailed bacteriophages are abundant and extremely diverse. Understanding this diversity is a challenge, and here we examine a small slice of that diversity in some detail. We contrast and compare the small genome, virulent, non-contractile tailed phages that infect the bacterial order Enterobacteriales. These phages, with genomes in the 35-60 kbp range, have very similar virions that are often difficult to distinguish by negative stain electron microscopy. There are currently 651 genome sequences of such phages in the public database. We show that these can be robustly parsed into fifteen well-defined clusters that have very different nucleotide sequences. We examine the similarities and differences among these clusters, as well as genetic exchange among clusters and the relationships between host species and phage clusters., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

We announce the complete genome sequences of 14 Serratia bacteriophages isolated from wastewater treatment plants. These phages define two previously undescribed types which we call the Carrot-like phage cluster (phages Carrot, BigDog, LittleDog, Niamh, Opt-148, Opt-169, PhooPhighters, Rovert, Serratianator, Stoker, Swain, and Ulliraptor) and Tlacuache-like phage cluster (Tlacuache and Opt-155).

Here, the full genome sequences of 22 T1-like bacteriophages isolated from wastewater are reported. Eight (BlueShadow, Brooksby, Devorator, ElisaCorrea, Reinasaurus, SorkZaugg, Supreme284, ZeroToHero) were isolated on Citrobacter , six on Klebsiella (Chell, FairDinkum, HazelMika, Opt-817, P528, PeteCarol), and eight on Escherichia (Fulano1, Mishu, Opt-719, PhleaSolo, Punny, Poky, Phunderstruck, Sadiya).

Proteus mirabilis and Klebsiella aerogenes are Gram-negative opportunistic pathogens that are responsible for nosocomial and health care-associated infections, including urinary tract infections. Here, the full genome sequences of six Chi-like Proteus (DanisaurMW, DoubleBarrel, Inception, Jing313, and NotEvenPhaged) or Klebsiella (Phraden) bacteriophages are announced, contributing to the understanding of Chi-like phages.

The Enterobacteriales order is composed of Gram-negative bacteria that range from harmless symbionts to well-studied pathogens. We announce complete genome sequences of five related SO-1-like Enterobacteriales bacteriophages (also known as the Dhillonvirus genus) isolated from wastewater that infect Escherichia coli (Opt-212, Over9000, Pubbukkers, and Teewinot) or Shigella boydii (StarDew).

Full genome sequences of five bacteriophages that were isolated from raw sewage samples and infect Enterobacteriales hosts are presented. Brookers is a P22-like Proteus phage, OddieOddie is a 9g-like Escherichia coli phage, Diencephelon is a Kp3-like Klebsiella phage, and Rgz1 and Lilpapawes are classic T4-like and T7-like virulent Proteus phages, respectively.

The highly contagious nature of SARS-CoV-2 has led to several studies on the transmission of the virus. A little studied potential fomite of great concern in the community is currency, which has been shown to harbor microbial pathogens in several studies. Since the onset of the COVID-19 pandemic, many businesses in the United States have limited the use of banknotes in favor of credit cards. However, SARS-CoV-2 has shown greater stability on plastic in several studies. Herein, the stability of SARS-CoV-2 at room temperature on banknotes, money cards and coins was investigated. In vitro studies with live virus suggested SARS-CoV-2 was highly unstable on banknotes, showing an initial rapid reduction in viable virus and no viral detection by 24 hours. In contrast, SARS-CoV-2 displayed increased stability on money cards with live virus detected after 48 hours. Environmental swabbing of currency and money cards on and near the campus of Brigham Young University supported these results, with no detection of SARS-CoV-2 RNA on banknotes, and a low level on money cards. However, no viable virus was detected on either. These preliminary results suggest that the use of money cards over banknotes in order to slow the spread of this virus may be ill-advised. These findings should be investigated further through larger environmental studies involving more locations., Competing Interests: The authors have declared that no competing interests exist.

In this case study, phage therapy was applied to treat a multidrug-resistant case of septicemic cutaneous ulcerative disease (SCUD) caused by Citrobacter freundii in a loggerhead sea turtle Caretta caretta. Phages were applied topically, intravenously, into the carapace, and into the exhibit water using various phage cocktails specific to the causative agent over an 8-month period. This was performed in conjunction with antimicrobial therapy. The animal was monitored through weekly cultures, photographs, and complete blood cell counts, as well as immune assays (phagocytosis, plasma lysozyme and superoxide dismutase activity, and plasma electrophoresis profiles). The animal, in comparison to an untreated, unaffected control, had elevated antibody titers to the administered phages, which persisted for at least 35 weeks. Although cultures were clear of C. freundii after phage treatment, the infection did return over time and immune assays confirmed deficiencies when compared to a healthy loggerhead sea turtle. Immune parameters with statistically significant changes over the study period included the following: decreased phagocytosis, increased alpha- and gamma-globulin protein components, and an increased albumin : globulin ratio. When C. freundii appeared again, the multidrug-resistant status had reverted back to normal susceptibility patterns. Although not completely known whether it was another subspecies of bacteria, the therapy did resolve the multidrug-resistant challenge. Phage therapy in combination with antimicrobial agents may be an effective treatment for sea turtles with normally functioning immune systems or less-severe infections. Additional research is needed to better understand and quantify sea turtle immunology., (© 2021 The Authors. Journal of Aquatic Animal Health published by Wiley Periodicals LLC on behalf of American Fisheries Society.)

Background: Metabolic phenotypes are the result of an intricate interplay between multiple factors, including diet, genotype, and the gut microbiome. Per-Arnt-Sim (PAS) kinase is a nutrient-sensing serine/threonine kinase, whose absence (PASK -/- ) protects against triglyceride accumulation, insulin resistance, and weight gain on a high-fat diet; conditions that are associated with dysbiosis of the gut microbiome. Methods: Herein, we report the metabolic effects of the interplay of diet (high fat high sugar, HFHS), genotype (PASK -/- ), and microbiome (16S sequencing). Results: Microbiome analysis identified a diet-induced, genotype-independent forked shift, with two discrete clusters of HFHS mice having increased beta and decreased alpha diversity. A "lower" cluster contained elevated levels of Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Defferibacteres , and was associated with increased weight gain, glucose intolerance, triglyceride accumulation, and decreased claudin-1 expression. Genotypic effects were observed within the clusters, lower cluster PASK -/- mice displayed increased weight gain and decreased triglyceride accumulation, whereas upper PASK -/- were resistant to decreased claudin-1. Conclusions: These results confirm previous reports that PAS kinase deficiency can protect mice against the deleterious effects of diet, and they suggest that microbiome imbalances can override protection. In addition, these results support a healthy diet for beneficial microbiome maintenance and suggest microbial culprits associated with metabolic disease.

Objectives: The purpose of this study was to measure low-rate binaural frequency modulation (FM) detection across the lifespan as a gauge of temporal fine structure processing. Children and older adults were expected to perform more poorly than young adults but for different reasons., Design: Detection of 2-Hz FM carried by a 500-Hz pure tone was measured for modulators that were either in-phase or out-of-phase across ears. Thresholds were measured in quiet and in noise. Participants were school-age children (n = 44), young adults (n = 11), and older adults (n = 17) with normal or near-normal hearing., Results: Thresholds were lower for out-of-phase than in-phase modulators among all listening groups. Detection thresholds improved with child age, with larger effects of age for dichotic than diotic FM. Introduction of masking noise tended to elevate thresholds; this effect was larger for the dichotic condition than the diotic condition, and larger for older adults than young adults. In noise, young adults received the greatest dichotic benefit, followed by older adults, then young children. The relative effects of noise on dichotic benefit did not differ for young adults compared to young children and older adults; however, young children saw greater reduction in benefit due to noise than older adults., Conclusion: The difference in dichotic benefit between children and young adults is consistent with maturation of central auditory processing. Differences in the effect of noise on dichotic benefit in young children and older adults support the idea that different factors or combinations of factors limit performance in these two groups. Although dichotic FM detection appears to be more sensitive to the effects of development and aging than diotic FM detection, the positive correlation between diotic and dichotic FM detection thresholds for all listeners suggests contribution of one or more factors common to both conditions., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

A recent genome-wide association study (GWAS) of 59 cerebrospinal fluid (CSF) proteins with a connection to Alzheimer's disease (AD) demonstrated an association between increased levels of chemokine ligand 2 (CCL2) with an atypical chemokine receptor chemokine-binding protein 2 variant V41A (ACKR2-V41A; rs2228467). High levels of CCL2 are associated with increased risk of AD development as well as other inflammatory diseases. In this study we characterized the biological function of the ACKR2-V41A receptor compared to the wild type allele by measuring its ligand binding affinity, CCL2 scavenging efficiency, and cell activation sensitivity. We transfected Chinese hamster ovary cells with plasmids carrying wild type ACKR2 (ACKR2-WT) or the mutant ACKR2-V41A receptor. Binding affinity assays showed that ACKR2-V41A has a lower binding affinity for CCL2 and CCL4 than ACKR2-WT. CCL2 scavenging results aligned with binding affinity assays, with ACKR2-V41A cells scavenging CCL2 with a lower efficiency than ACKR2-WT. Cell activation assays also showed that ACKR2-V41A cells had significantly lower receptor upregulation (β-Arrestin-dependent signaling pathway) upon stimulation compared to ACKR2-WT cells. These findings provide molecular and biological mechanistic insights into the GWAS association of ACKR2-V41A with increased levels of CCL2 in CSF and possibly other chemokine ligands. Increased CCL2 levels are associated with accelerated cognitive decline and increased risk of AD. Understanding how this atypical chemokine receptor allele increases serum markers of inflammation could lead to novel therapeutic solutions for AD.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with no known cure. Approximately 90% of ALS cases are sporadic, suggesting there are multiple contributing factors that influence the disease risk, onset, and progression. Diet and sex are two factors that have been reported to alter ALS risk, onset and progression in humans and in animal models, providing potential modifiers of disease. Several epidemiological studies have identified diets that positively affect ALS patients, including various high-calorie fat or sugar-based diets, while animal models have been developed to test how these diets are working on a molecular level. These diets may offset the metabolic alterations that occur in ALS, such as hypermetabolism, lowered body mass index(BMI), and hyperlipidemia. Sex-dependent differences have also come forth from large-scale epidemiological studies as well as mouse-model studies. In addition, sex hormones have been shown to affect disease risk or progression. Herein, studies on the effects of diet and sex on ALS risk, onset, and progression will be reviewed. Understanding these diet- and sex-dependent outcomes may lead to optimized patient-specific therapies for ALS., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Klebsiella pneumoniae is a pathogen responsible for significant proportions of nosocomial and health care-associated infections and is known to acquire multiple antibiotic resistance genes. Here, we announce the full genome sequences of 12 K. pneumoniae bacteriophages from samples collected in wastewater treatment facilities across the western United States., (Copyright © 2020 Thurgood et al.)

The purpose of this study was to measure the binaural interaction component (BIC) derived from click-evoked auditory brainstem responses (ABRs) using stimuli configured to elicit the Precedence Effect. The hypothesis was that the contribution of binaural processing to echo suppression can be evidenced by a diminished or absent BIC associated with the echo. Ten normal-hearing young adults provided ABRs generated by sequences of click pairs. Results showed that BICs elicited by diotic clicks in isolation were obliterated when those diotic clicks were preceded by a click pair having an interaural time difference of 400 µs and where the interclick interval was 8.4 ms. The presence of the leading click pair increased the latency of the ABR generated by the lagging diotic click pair but did not decrease its amplitude. The results were interpreted as indicating a contribution of binaural processing at the level of the brainstem to echo suppression, at least for the conditions tested here.

Here, the genome sequences of two soil bacteriophages isolated from a red chili plantation in Indonesia are presented. The genome of vB_BspS_SplendidRed (42,859 bp) is highly similar to Bacillus phage Ray17 from the United States, while vB_BspM_MarvelLand (156,945 bp) is highly similar to Bacillus phage BC01 from South Korea., (Copyright © 2019 Handoko et al.)

Erwinia and Pantoea are closely related bacterial plant pathogens in the Gram negative Enterobacteriales order. Sixty tailed bacteriophages capable of infecting these pathogens have been completely sequenced by investigators around the world and are in the current databases, 30 of which were sequenced by our lab. These 60 were compared to 991 other Enterobacteriales bacteriophage genomes and found to be, on average, just over twice the overall average length. These Erwinia and Pantoea phages comprise 20 clusters based on nucleotide and protein sequences. Five clusters contain only phages that infect the Erwinia and Pantoea genera, the other 15 clusters are closely related to bacteriophages that infect other Enterobacteriales; however, within these clusters the Erwinia and Pantoea phages tend to be distinct, suggesting ecological niche may play a diversification role. The failure of many of their encoded proteins to have predicted functions highlights the need for further study of these phages., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Masked speech recognition in normal-hearing listeners depends in part on masker type and semantic context of the target. Children and older adults are more susceptible to masking than young adults, particularly when the masker is speech. Semantic context has been shown to facilitate noise-masked sentence recognition in all age groups, but it is not known whether age affects a listener's ability to use context with a speech masker. The purpose of the present study was to evaluate the effect of masker type and semantic context of the target as a function of listener age., Design: Listeners were children (5 to 16 years), young adults (19 to 30 years), and older adults (67 to 81 years), all with normal or near-normal hearing. Maskers were either speech-shaped noise or two-talker speech, and targets were either semantically correct (high context) sentences or semantically anomalous (low context) sentences., Results: As predicted, speech reception thresholds were lower for young adults than either children or older adults. Age effects were larger for the two-talker masker than the speech-shaped noise masker, and the effect of masker type was larger in children than older adults. Performance tended to be better for targets with high than low semantic context, but this benefit depended on age group and masker type. In contrast to adults, children benefitted less from context in the two-talker speech masker than the speech-shaped noise masker. Context effects were small compared with differences across age and masker type., Conclusions: Different effects of masker type and target context are observed at different points across the lifespan. While the two-talker masker is particularly challenging for children and older adults, the speech masker may limit the use of semantic context in children but not adults.

Erwinia amylovora is a plant pathogen from the Erwiniaceae family and a causative agent of the devastating agricultural disease fire blight. Here we characterize eight lytic bacteriophages of E. amylovora that we isolated from the Wasatch front (Utah, United States) that are highly similar to vB_EamM_Ea35-70 which was isolated in Ontario, Canada. With the genome size ranging from 271 to 275 kb, this is a novel jumbo family of bacteriophages. These jumbo bacteriophages were further characterized through genomic and proteomic comparison, mass spectrometry, host range and burst size. Their proteomes are highly unstudied, with over 200 putative proteins with no known homologs. The production of 27 of these putative proteins was confirmed by mass spectrometry analysis. These bacteriophages appear to be most similar to bacteriophages that infect Pseudomonas and Ralstonia rather than Enterobacteriales bacteria by protein similarity, however, we were only able to detect infection of Erwinia and the closely related strains of Pantoea .

Objective: The purpose of this study was to investigate perceptual and electrophysiological encoding of complex periodic signals as a function of age. Design: Two groups of adults completed three listening tasks: a behavioural task of detection of a mistuned harmonic component in a complex tone, an electrophysiological measure of speech-evoked auditory brainstem response (sABR), and a speech-in-noise measure. Between group comparisons were undertaken for each task as well as pairwise correlation analyses for all tasks. Study sample: One group of younger adults ( n  = 20) and one group of older adults ( n  = 20) participated. All listeners had relatively normal audiometric thresholds (≤20 dB HL) from 250-4000 Hz. Results: Younger adults had better results than the older adults on all three tasks: sensitivity for detecting a mistuned harmonic, spectral encoding for sABR, and release from masking for the speech-in-noise test. There were no significant correlations between measures when evaluating the older adults in isolation. Conclusions: The results are consistent with the body of literature that demonstrates reduced temporal processing abilities for older adults. The combined method approach undertaken in this investigation did not result in correlations between the perceptual and electrophysiological measures of temporal processing.

Objectives: The purpose of this study was to obtain an electrophysiological analog of masking release using speech-evoked cortical potentials in steady and modulated maskers and to relate this masking release to behavioral measures for the same stimuli. The hypothesis was that the evoked potentials can be tracked to a lower stimulus level in a modulated masker than in a steady masker and that the magnitude of this electrophysiological masking release is of the same order as that of the behavioral masking release for the same stimuli., Design: Cortical potentials evoked by an 80-ms /ba/ stimulus were measured in two steady maskers (30 and 65 dB SPL), and in a masker that modulated between these two levels at a rate of 25 Hz. In each masker, a level series was undertaken to determine electrophysiological threshold. Behavioral detection thresholds were determined in the same maskers using an adaptive tracking procedure. Masking release was defined as the difference between signal thresholds measured in the steady 65-dB SPL masker and the modulated masker. A total of 23 normal-hearing adults participated., Results: Electrophysiological thresholds were uniformly elevated relative to behavioral thresholds by about 6.5 dB. However, the magnitude of masking release was about 13.5 dB for both measurement domains., Conclusions: Electrophysiological measures of masking release using speech-evoked cortical auditory evoked potentials correspond closely to behavioral estimates for the same stimuli. This suggests that objective measures based on electrophysiological techniques can be used to reliably gauge aspects of temporal processing ability.

Two experiments were performed to better understand on- and off-frequency modulation masking in normal-hearing school-age children and adults. Experiment 1 estimated thresholds for detecting 16-, 64- or 256-Hz sinusoidal amplitude modulation (AM) imposed on a 4300-Hz pure tone. Thresholds tended to improve with age, with larger developmental effects for 64- and 256-Hz AM than 16-Hz AM. Detection of 16-Hz AM was also measured with a 1000-Hz off-frequency masker tone carrying 16-Hz AM. Off-frequency modulation masking was larger for younger than older children and adults when the masker was gated with the target, but not when the masker was continuous. Experiment 2 measured detection of 16- or 64-Hz sinusoidal AM carried on a bandpass noise with and without additional on-frequency masker AM. Children and adults demonstrated modulation masking with similar tuning to modulation rate. Rate-dependent age effects for AM detection on a pure-tone carrier are consistent with maturation of temporal resolution, an effect that may be obscured by modulation masking for noise carriers. Children were more susceptible than adults to off-frequency modulation masking for gated stimuli, consistent with maturation in the ability to listen selectively in frequency, but the children were not more susceptible to on-frequency modulation masking than adults.

Masked sentence recognition was evaluated in normal-hearing children (8.8-10.5 years), young adults (18-28 years), and older adults (60-71 years). Consistent with published data, speech recognition thresholds were poorer for young children and older adults than for young adults, particularly when the masker was composed of speech. Psychometric function slopes were steeper for young children and older adults than for young adults when the masker was two-talker speech, but not when it was speech-shaped noise. Multiple factors are implicated in the age effects observed for speech-in-speech recognition at low signal-to-noise ratios.

PAS kinase 1 (Psk1) is a key regulator of respiration in Saccharomyces cerevisiae Herein the molecular mechanisms of this regulation are explored through the characterization of its substrate, Centromere binding factor 1 (Cbf1). CBF1 -deficient yeast displayed a significant decrease in cellular respiration, while PAS kinase-deficient yeast, or yeast harboring a Cbf1 phosphosite mutant (T211A) displayed a significant increase. Transmission electron micrographs showed an increased number of mitochondria in PAS kinase-deficient yeast consistent with the increase in respiration. Although the CBF1 -deficient yeast did not appear to have an altered number of mitochondria, a mitochondrial proteomics study revealed significant differences in the mitochondrial composition of CBF1 -deficient yeast including altered Atp3 levels, a subunit of the mitochondrial F 1 -ATP synthase complex. Both beta-galactosidase reporter assays and western blot analysis confirmed direct transcriptional control of ATP3 by Cbf1 In addition, we confirmed the regulation of yeast lipid genes LAC1 and LAG1 by Cbf1 The human homolog of Cbf1, Upstream transcription factor 1 (USF1), is also known to be involved in lipid biogenesis. Herein, we provide the first evidence for a role of USF1 in respiration since it appeared to complement Cbf1 in vivo as determined by respiration phenotypes. In addition, we confirmed USF1 as a substrate of human PAS kinase (hPASK) in vitro Combined, our data supports a model in which Cbf1/USF1 functions to partition glucose toward respiration and away from lipid biogenesis, while PAS kinase inhibits respiration in part through the inhibition of Cbf1/USF1., (Copyright © 2019 DeMille et al.)