Source level of wind-generated ambient sound in the oceana).

Inference of source levels for ambient ocean sound from local wind at the sea surface requires an assumption about the nature of the sound source. Depending upon the assumptions made about the nature of the sound source, whether monopole or dipole distributions, the estimated source levels from different research groups are different by several decibels over the frequency band 10-350 Hz. This paper revisits the research issues of source level of local wind-generated sound and shows that the differences in estimated source levels can be understood through a simple analysis of the source assumptions.

Short-Term Dietary Intervention with Whole Oats Protects from Antibiotic-Induced Dysbiosis.

Antibiotic-induced gut microbiome dysbiosis (AID) is known to be influenced by host dietary composition. However, how and when diet modulates gut dysbiosis remains poorly characterized. Thus, here, we utilize a multi-omics approach to characterize how a diet supplemented with oats, a rich source of microbiota-accessible carbohydrates, or dextrose impacts amoxicillin-induced changes to gut microbiome structure and transcriptional activity. We demonstrate that oat administration during amoxicillin challenge provides greater protection from AID than the always oats or recovery oats diet groups. In particular, the group in which oats were provided at the time of antibiotic exposure induced the greatest protection against AID while the other oat diets saw greater effects after amoxicillin challenge. The oat diets likewise reduced amoxicillin-driven elimination of Firmicutes compared to the dextrose diet. Functionally, gut communities fed dextrose were carbohydrate starved and favored respiratory metabolism and consequent metabolic stress management while oat-fed communities shifted their transcriptomic profile and emphasized antibiotic stress management. The metabolic trends were exemplified when assessing transcriptional activity of the following two common gut commensal bacteria: Akkermansia muciniphila and Bacteroides thetaiotaomicron. These findings demonstrate that while host diet is important in shaping how antibiotics effect the gut microbiome composition and function, diet timing may play an even greater role in dietary intervention-based therapeutics. IMPORTANCE We utilize a multi-omics approach to demonstrate that diets supplemented with oats, a rich source of microbiota-accessible carbohydrates, are able to confer protection against antibiotic-induced dysbiosis (AID). Our findings affirm that not only is host diet important in shaping antibiotics effects on gut microbiome composition and function but also that the timing of these diets may play an even greater role in managing AID. This work provides a nuanced perspective on dietary intervention against AID and may be informative on preventing AID during routine antibiotic treatment.

Content and delivery preferences for information to support the management of high blood pressure.

Blood pressure(BP) management interventions have been shown to be more effective when accompanied by appropriate patient education. As high BP remains poorly controlled, there may be gaps in patient knowledge and education. Therefore, this study aimed to identify specific content and delivery preferences for information to support BP management among Australian adults from the general public. Given that BP management is predominantly undertaken by general practitioners(GPs), information preferences to support BP management were also ascertained from a small sample of Australian GPs. An online survey of adults was conducted to identify areas of concern for BP management to inform content preferences and preferred format for information delivery. A separate online survey was also delivered to GPs to determine preferred information sources to support BP management. Participants were recruited via social media. General public participants (n = 465) were mostly female (68%), >60 years (57%) and 49% were taking BP-lowering medications. The management of BP without medications, and role of lifestyle in BP management were of concern among 30% and 26% of adults respectively. Most adults (73%) preferred to access BP management information from their GP. 57% of GPs (total n = 23) preferred information for supporting BP management to be delivered via one-page summaries. This study identified that Australian adults would prefer more information about the management of BP without medications and via lifestyle delivered by their GP. This could be achieved by providing GPs with one-page summaries on relevant topics to support patient education and ultimately improve BP management.

Comparative genomics of white and opaque cell states supports an epigenetic mechanism of phenotypic switching in Candida albicans.

Several Candida species can undergo a heritable and reversible transition from a 'white' state to a mating proficient 'opaque' state. This ability relies on highly interconnected transcriptional networks that control cell-type-specific gene expression programs over multiple generations. Candida albicans, the most prominent pathogenic Candida species, provides a well-studied paradigm for the white-opaque transition. In this species, a network of at least eight transcriptional regulators controls the balance between white and opaque states that have distinct morphologies, transcriptional profiles, and physiological properties. Given the reversible nature and the high frequency of white-opaque transitions, it is widely assumed that this switch is governed by epigenetic mechanisms that occur independently of any changes in DNA sequence. However, a direct genomic comparison between white and opaque cells has yet to be performed. Here, we present a whole-genome comparative analysis of C. albicans white and opaque cells. This analysis revealed rare genetic changes between cell states, none of which are linked to white-opaque switching. This result is consistent with epigenetic mechanisms controlling cell state differentiation in C. albicans and provides direct evidence against a role for genetic variation in mediating the switch.

The extrachromosomal elements of the Naegleria genus: How little we know.

There are currently 47 characterized species in the Naegleria genus of free-living amoebae. Each amoeba has thousands of extrachromosomal elements that are closed circular structures comprised of a single ribosomal DNA (rDNA) copy and a large non-rDNA sequence. Despite the presence of putative open reading frames and introns, ribosomal RNA is the only established transcript. A single origin of DNA replication (ori) has been mapped within the non-rDNA sequence for one species (N. gruberi), a finding that strongly indicates that these episomes replicate independently of the cell's chromosomal DNA component. This article reviews that which has been published about these interesting DNA elements and by analyzing available sequence data, discusses the possibility that different phylogenetically related clusters of Naegleria species individually conserve ori structures and suggests where the rRNA promoter and termination sites may be located.

Robust estimation of sediment sound speed from the group speed of the critical mode.

In the ocean waveguide, the sediment sound speed has a simple relationship with the group speed of the highest order mode that propagates close to the critical angle. The paper shows that robust estimates of the sound speed are obtained from estimates of the "critical" mode group speed determined from analysis of the energy distribution of the time-warped spectrum of a broadband signal. The method is applied to experimental data collected in the Yellow Sea of China. Estimated sound speeds agreed closely with expected values for clayey slit (1531 m/s) and sandy silt (1593 m/s) sediment at the sites.

Replication of a rare risk haplotype on 1p36.33 for autism spectrum disorder.

Hundreds of genes have been implicated in autism spectrum disorders (ASDs). In genetically heterogeneous conditions, large families with multiple affected individuals provide strong evidence implicating a rare variant, and replication of the same variant in multiple families is unusual. We previously published linkage analyses and follow-up exome sequencing in seven large families with ASDs, implicating 14 rare exome variants. These included rs200195897, which was transmitted to four affected individuals in one family. We attempted replication of those variants in the MSSNG database. MSSNG is a unique resource for replication of ASD risk loci, containing whole genome sequence (WGS) on thousands of individuals diagnosed with ASDs and family members. For each exome variant, we obtained all carriers and their relatives in MSSNG, using a TDT test to quantify evidence for transmission and association. We replicated the transmission of rs200195897 to four affected individuals in three additional families. rs200195897 was also present in three singleton affected individuals, and no unaffected individuals other than transmitting parents. We identified two additional rare variants (rs566472488 and rs185038034) transmitted with rs200195897 on 1p36.33. Sanger sequencing confirmed the presence of these variants in the original family segregating rs200195897. To our knowledge, this is the first example of a rare haplotype being transmitted with ASD in multiple families. The candidate risk variants include a missense mutation in SAMD11, an intronic variant in NOC2L, and a regulatory region variant close to both genes. NOC2L is a transcription repressor, and several genes involved in transcription regulation have been previously associated with ASDs.

Galleria mellonella as an insect model for P. destructans, the cause of White-nose Syndrome in bats.

Pseudogymnoascus destructans is the fungal pathogen responsible for White-nose Syndrome (WNS), a disease that has killed millions of bats in North America over the last decade. A major obstacle to research on P. destructans has been the lack of a tractable infection model for monitoring virulence. Here, we establish a high-throughput model of infection using larvae of Galleria mellonella, an invertebrate used to study host-pathogen interactions for a wide range of microbial species. We demonstrate that P. destructans can kill G. mellonella larvae in an inoculum-dependent manner when infected larvae are housed at 13°C or 18°C. Larval killing is an active process, as heat-killed P. destructans spores caused significantly decreased levels of larval death compared to live spores. We also show that fungal spores that were germinated prior to inoculation were able to kill larvae 3-4 times faster than non-germinated spores. Lastly, we identified chemical inhibitors of P. destructans and used G. mellonella to evaluate these inhibitors for their ability to reduce virulence. We demonstrate that amphotericin B can effectively block larval killing by P. destructans and thereby establish that this infection model can be used to screen biocontrol agents against this fungal pathogen.

Variants regulating ZBTB4 are associated with age-at-onset of Alzheimer's disease.

The identification of novel genetic modifiers of age-at-onset (AAO) of Alzheimer's disease (AD) could advance our understanding of AD and provide novel therapeutic targets. A previous genome scan for modifiers of AAO among families affected by early-onset AD caused by the PSEN2 N141I variant identified 2 loci with significant evidence for linkage: 1q23.3 and 17p13.2. Here, we describe the fine-mapping of these 2 linkage regions, and test for replication in 6 independent datasets. By fine-mapping these linkage signals in a single large family, we reduced the linkage regions to 11% their original size and nominated 54 candidate variants. Among the 11 variants associated with AAO of AD in a larger sample of Germans from Russia, the strongest evidence implicated promoter variants influencing NCSTN on 1q23.3 and ZBTB4 on 17p13.2. The association between ZBTB4 and AAO of AD was replicated by multiple variants in independent, trans-ethnic datasets. Our results show association between AAO of AD and both ZBTB4 and NCSTN. ZBTB4 is a transcriptional repressor that regulates the cell cycle, including the apoptotic response to amyloid beta, while NCSTN is part of the gamma secretase complex, known to influence amyloid beta production. These genes therefore suggest important roles for amyloid beta and cell cycle pathways in AAO of AD.

A simple expression for sound attenuation due to surface duct energy leakage in low-latitude oceans.

This paper presents an expression for the attenuation of sound energy in an ocean surface duct due to energy leakage outside the duct. Dominant parameters determining the attenuation are the sound frequency and the surface duct thickness. The attenuation is found to be exponentially dependent on a scaled frequency that combines the two parameters. Data from experiments in low-latitude oceans with three different surface duct thicknesses are used to verify the exponential expression derived for the attenuation.

Domain I of the 5' non-translated genomic region in coxsackievirus B3 RNA is not required for productive replication.

Domain I is a cloverleaf-like secondary structure at the 5' termini of all enterovirus genomes, comprising part of a cis-acting replication element essential for efficient enteroviral replication. 5' genomic terminal deletions up to as much as 55% of domain I can occur without lethality following coxsackie B virus infections. We report here that the entire CVB structural domain I can be deleted without lethality.

Sequential inversion of modal data for sound attenuation in sediment at the New Jersey Shelf.

This paper presents a method for estimating bottom geoacoustic properties especially the sediment attenuation from information contained in normal modes of a broadband signal. Propagating modes are resolved using the time-warping technique applied to signals from light bulb sound sources deployed at ranges of 5 and 7 km in the Shallow Water '06 experiment. A sequential inversion approach is designed that uses specific features of the acoustic data that are highly sensitive to specific geoacoustic model parameters. The first feature is the modal group speed, which is inverted for seabed sound speed, density, and sediment thickness. The second feature is the modal depth function for inverting receiver depths. The third feature is related to the modal coefficient spectra, and this is inverted for source depth and sediment attenuation. In each subsequent stage, estimates from the previous stage(s) are used as known values. The sequential inversion is stable and generates estimates for the geoacoustic model parameters that agree very well with results from other experiments carried out in the same region. Notably, the inversion obtains an estimated attenuation of 0.078 dB/λ in the band 120-180 Hz for the de-watered marine sediment characteristic of the continental shelf at the site.

Mutational Disruption of cis-Acting Replication Element 2C in Coxsackievirus B3 Leads to 5'-Terminal Genomic Deletions.

UNLABELLED: Following natural human or experimental murine infections and in cell culture, coxsackievirus B (CVB) RNA can persist for weeks in the absence of a cytopathic effect, yet viral RNA remains detectable. Our earlier studies demonstrated that this persistence produced viral RNA with up to 49 nucleotide deletions at the genomic 5' terminus which partially degraded the cloverleaf (or domain I), an RNA structure required for efficient viral replication. A cis-acting replication element (CRE) in the 2C protein-coding region [CRE(2C)] templates the addition of two uridine residues to the virus genome-encoded RNA replication primer VPg prior to positive-strand synthesis. Because our previous work also demonstrated that the genomes of CVB with a 5'-terminal deletion (CVB-TD) have VPg covalently linked, even though they rarely terminate in the canonical UU donated by CRE(2C)-mediated uridylylation of VPg, we hypothesized that a functional (uridylylating) CRE(2C) would be unnecessary for CVB-TD replication. Using the same 16 mutations in the CVB3 CRE(2C) structure that were considered lethal for this virus by others, we demonstrate here both in infected cell cultures and in mice that wild-type (wt) and CVB3-TD strains carrying these mutations with a nonuridylylating CRE(2C) are viable. While the wt genome with the mutated CRE(2C) displays suppressed replication levels similar to those observed in a CVB3-TD strain, mutation of the CRE(2C) function in a CVB3-TD strain does not further decrease replication. Finally, we show that replication of the parental CVB3 strain containing the mutated CRE(2C) drives the de novo generation of genomic deletions at the 5' terminus. IMPORTANCE: In this report, we demonstrate that while CVB can replicate without a uridylylating CRE(2C), the replication rate suffers significantly. Further, deletions at the 5' terminus of the genome are generated in this virus population, with this virus population supplanting the wild-type population. This demonstrates that VPg can prime without being specifically uridylylated and that this priming is error prone, resulting in the loss of sequence information from the 5' terminus. These findings have significance when considering the replication of human enteroviruses, and we believe that these data are unattainable in a cell-free system due to the poor replication of these CRE-deficient viruses.

Inheritance of thelytoky in the honey bee Apis mellifera capensis.

Asexual reproduction via thelytokous parthenogenesis is widespread in the Hymenoptera, but its genetic underpinnings have been described only twice. In the wasp Lysiphlebus fabarum and the Cape honey bee Apis mellifera capensis the origin of thelytoky have each been traced to a single recessive locus. In the Cape honey bee it has been argued that thelytoky (th) controls the thelytoky phenotype and that a deletion of 9 bp in the flanking intron downstream of exon 5 (tae) of the gemini gene switches parthenogenesis from arrhenotoky to thelytoky. To further explore the mode of inheritance of thelytoky, we generated reciprocal backcrosses between thelytokous A. m. capensis and the arrhenotokous A. m. scutellata. Ten genetic markers were used to identify 108 thelytokously produced offspring and 225 arrhenotokously produced offspring from 14 colonies. Patterns of appearance of thelytokous parthenogenesis were inconsistent with a single locus, either th or tae, controlling thelytoky. We further show that the 9 bp deletion is present in the arrhenotokous A. m. scutellata population in South Africa, in A. m. intermissa in Morocco and in Africanized bees from Brazil and Texas, USA, where thelytoky has not been reported. Thus the 9 p deletion cannot be the cause of thelytoky. Further, we found two novel tae alleles. One contains the previously described 9 bp deletion and an additional deletion of 7 bp nearby. The second carries a single base insertion with respect to the wild type. Our data are consistent with the putative th locus increasing reproductive capacity.

Pharmacokinetics and effects on thromboxane B2 production following intravenous administration of flunixin meglumine to exercised thoroughbred horses.

Flunixin meglumine is commonly used in horses for the treatment of musculoskeletal injuries. The current ARCI threshold recommendation is 20 ng/mL when administered at least 24 h prior to race time. In light of samples exceeding the regulatory threshold at 24 h postadministration, the primary goal of the study reported here was to update the pharmacokinetics of flunixin following intravenous administration, utilizing a highly sensitive liquid chromatography-mass spectrometry (LC-MS). An additional objective was to characterize the effects of flunixin on COX-1 and COX-2 inhibition when drug concentrations reached the recommended regulatory threshold. Sixteen exercised adult horses received a single intravenous dose of 1.1 mg/kg. Blood samples were collected up to 72 h postadministration and analyzed using LC-MS. Blood samples were collected from 8 horses for determination of TxB(2) and PGE(2) concentrations prior to and up to 96 h postflunixin administration. Mean systemic clearance, steady-state volume of distribution and terminal elimination half-life was 0.767 ± 0.098 mL/min/kg, 0.137 ± 0.12 L/kg, and 4.8 ± 1.59 h, respectively. Four of the 16 horses had serum concentrations in excess of the current ARCI recommended regulatory threshold at 24 h postadministration. TxB(2) suppression was significant for up to 24 h postadministration.

Inversion of acoustical data from the "Shallow Water 06" experiment by statistical signal characterization.

This paper presents an application to validate an acoustic signal characterization scheme for ocean acoustic tomography and geoacoustic inversions proposed by Taroudakis, Tzagkarakis, and Tsakalides [J. Acoust. Soc. Am. 119, 1396-1405 (2006)] using data from an experiment at sea. The data were collected during the Shallow water '06 (SW06) experiment off the New Jersey Continental Shelf and the inversion results (sea-bed geoacoustic parameters and source range) are compared with those reported from the same data by Bonnel and Chapman [J. Acoust. Soc. Am. 130(2), EL101-EL107 (2011)]. The comparison and the signal reconstruction using estimated values of the model parameters are satisfactory indicating that the new signal characterization method is useful for practical applications of acoustical oceanography.

Inversion of seabed attenuation using time-warping of close range data.

An inversion scheme based on time-warping is presented for estimating seabed sound attenuation from modal dispersion of close-range single-hydrophone data. The dispersion information is extracted directly from the warped signal spectrum. Seabed sound speed and density are inverted from the modal group velocity curves, and the attenuation is inverted from the normalized modal amplitudes. The method is applied to experimental data collected in the Yellow Sea of China during the winter of 2002. The inverted sound speed and density are consistent with the sand-silt-clay sediment at the site, and the attenuation is nonlinear over the frequency band from 125-500 Hz.