The marine soundscape of the Perth Canyon

The Perth Canyon is a submarine canyon off Rottnest Island in Western Australia. It is rich in biodiversity in general, and important as a feeding and resting ground for great whales on migration. Australia's Integrated Marine Observing System (IMOS) has moorings in the Perth Canyon monitoring its acoustical, physical and biological oceanography. Data from these moorings, as well as weather data from a near-by Bureau of Meteorology weather station on Rottnest Island and ship traffic data from the Australian Maritime Safety Authority were correlated to characterise and quantify the marine soundscape between 5 and 3000. Hz, consisting of its geophony, biophony and anthrophony. Overall, biological sources are a strong contributor to the soundscape at the IMOS site, with whales dominating seasonally at low (15-100. Hz) and mid frequencies (200-400. Hz), and fish or invertebrate choruses dominating at high frequencies (1800-2500. Hz) at night time throughout the year. Ships contribute significantly to the 8-100. Hz band at all times of the day, all year round, albeit for a few hours at a time only. Wind-dependent noise is significant at 200-3000. Hz; winter rains are audible underwater at 2000-3000. Hz. We discuss how passive acoustic data can be used as a proxy for ocean weather. Passive acoustics is an efficient way of monitoring animal visitation times and relative densities, and potential anthropogenic influences

Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19

Background - Gut microbiota alterations have been reported in hospitalized COVID-19 patients, with reduced alpha diversity and altered microbiota composition related to respiratory failure. However, data regarding gut microbiota and mortality are scarce. Methods - Rectal swabs for gut microbiota analyses were collected within 48 h after hospital admission (baseline; n = 123) and three-month post-admission (n = 50) in a subset of patients included in the Norwegian SARS-CoV2 cohort study. Samples were analysed by sequencing the 16S rRNA gene. Gut microbiota diversity and composition at baseline were assessed in relation to need for intensive care unit (ICU) admission during hospitalization. The primary objective was to investigate whether the ICU-related gut microbiota was associated with 60-day mortality. Results - Gut microbiota diversity (Shannon index) at baseline was lower in COVID-19 patients requiring ICU admission during hospitalization than in those managed in general wards. A dysbiosis index representing a balance of enriched and reduced taxa in ICU compared with ward patients, including decreased abundance of butyrate-producing microbes and enrichment of a partly oral bacterial flora, was associated with need of ICU admission independent of antibiotic use, dexamethasone use, chronic pulmonary disease, PO2/FiO2 ratio, C-reactive protein, neutrophil counts or creatinine levels (adjusted p  Conclusions - Although our data should be regarded as exploratory due to low number of clinical end points, they suggest that gut microbiota alterations during hospitalization could be related to poor prognosis after severe COVID-19. Larger studies of gut involvement during COVID-19 in relation to long-term clinical outcome are warranted

Noiseonomics: The relationship between ambient noise levels in the sea and global economic trends

In recent years, the topic of noise in the sea and its effects on marine mammals has attracted considerable attention from both the scientific community and the general public. Since marine mammals rely heavily on acoustics as a primary means of communicating, navigating, and foraging in the ocean, any change in their acoustic environment may have an impact on their behavior. Specifically, a growing body of literature suggests that low-frequency, ambient noise levels in the open ocean increased approximately 3.3 dB per decade during the period 1950–2007. Here we show that this increase can be attributed primarily to commercial shipping activity, which in turn, can be linked to global economic growth. As a corollary, we conclude that ambient noise levels can be directly related to global economic conditions. We provide experimental evidence supporting this theory and discuss its implications for predicting future noise levels based on global economic trends

Circulating markers of extracellular matrix remodelling in severe COVID-19 patients

Background Abnormal remodelling of the extracellular matrix (ECM) has generally been linked to pulmonary inflammation and fibrosis and may also play a role in the pathogenesis of severe COVID-19. To further elucidate the role of ECM remodelling and excessive fibrogenesis in severe COVID-19, we examined circulating levels of mediators involved in various aspects of these processes in COVID-19 patients. Methods Serial blood samples were obtained from two cohorts of hospitalised COVID-19 patients (n = 414). Circulating levels of ECM remodelling mediators were quantified by enzyme immunoassays in samples collected during hospitalisation and at 3-month follow-up. Samples were related to disease severity (respiratory failure and/or treatment at the intensive care unit), 60-day total mortality and pulmonary pathology after 3-months. We also evaluated the direct effect of inactivated SARS-CoV-2 on the release of the different ECM mediators in relevant cell lines. Results Several of the measured markers were associated with adverse outcomes, notably osteopontin (OPN), S100 calcium-binding protein A12 and YKL-40 were associated with disease severity and mortality. High levels of ECM mediators during hospitalisation were associated with computed tomography thorax pathology after 3-months. Some markers (i.e. growth differential factor 15, galectin 3 and matrix metalloproteinase 9) were released from various relevant cell lines (i.e. macrophages and lung cell lines) in vitro after exposure to inactivated SARS-CoV-2 suggesting a direct link between these mediators and the causal agent of COVID-19. Conclusion Our findings highlight changes to ECM remodelling and particularly a possible role of OPN, S100A12 and YKL-40 in the pathogenesis of severe COVID-19

Coregulator Control of Androgen Receptor Action by a Novel Nuclear Receptor-Binding Motif

The androgen receptor (AR) is a ligand-activated transcription factor that is essential for prostate cancer development. It is activated by androgens through its ligand-binding domain (LBD), which consists predominantly of 11 α-helices. Upon ligand binding, the last helix is reorganized to an agonist conformation termed activator function-2 (AF-2) for coactivator binding. Several coactivators bind to the AF-2 pocket through conserved LXXLL or FXXLF sequences to enhance the activity of the receptor. Recently, a small compound-binding surface adjacent to AF-2 has been identified as an allosteric modulator of the AF-2 activity and is termed binding function-3 (BF-3). However, the role of BF-3 in vivo is currently unknown, and little is understood about what proteins can bind to it. Here we demonstrate that a duplicated GARRPR motif at the N terminus of the cochaperone Bag-1L functions through the BF-3 pocket. These findings are supported by the fact that a selective BF-3 inhibitor or mutations within the BF-3 pocket abolish the interaction between the GARRPR motif(s) and the BF-3. Conversely, amino acid exchanges in the two GARRPR motifs of Bag-1L can impair the interaction between Bag-1L and AR without altering the ability of Bag-1L to bind to chromatin. Furthermore, the mutant Bag-1L increases androgen-dependent activation of a subset of AR targets in a genome-wide transcriptome analysis, demonstrating a repressive function of the GARRPR/BF-3 interaction. We have therefore identified GARRPR as a novel BF-3 regulatory sequence important for fine-tuning the activity of the AR

Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients

The new SARS-CoV-2 pandemic leads to COVID-19 with respiratory failure, substantial morbidity, and significant mortality. Overactivation of the innate immune response is postulated to trigger this detrimental process. The complement system is a key player in innate immunity. Despite a few reports of local complement activation, there is a lack of evidence that the degree of systemic complement activation occurs early in COVID-19 patients, and whether this is associated with respiratory failure. This study shows that a number of complement activation products are systemically, consistently, and long-lastingly increased from admission and during the hospital stay. Notably, the terminal sC5b-9 complement complex was associated with respiratory failure. Thus, complement inhibition is an attractive therapeutic approach for treatment of COVD-19

Wind, waves, and acoustic background levels at Station ALOHA

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 117 (2012): C03017, doi:10.1029/2011JC007267.Frequency spectra from deep-ocean near-bottom acoustic measurements obtained contemporaneously with wind, wave, and seismic data are described and used to determine the correlations among these data and to discuss possible causal relationships. Microseism energy appears to originate in four distinct regions relative to the hydrophone: wind waves above the sensors contribute microseism energy observed on the ocean floor; a fraction of this local wave energy propagates as seismic waves laterally, and provides a spatially integrated contribution to microseisms observed both in the ocean and on land; waves in storms generate microseism energy in deep water that travels as seismic waves to the sensor; and waves reflected from shorelines provide opposing waves that add to the microseism energy. Correlations of local wind speed with acoustic and seismic spectral time series suggest that the local Longuet-Higgins mechanism is visible in the acoustic spectrum from about 0.4 Hz to 80 Hz. Wind speed and acoustic levels at the hydrophone are poorly correlated below 0.4 Hz, implying that the microseism energy below 0.4 Hz is not typically generated by local winds. Correlation of ocean floor acoustic energy with seismic spectra from Oahu and with wave spectra near Oahu imply that wave reflections from Hawaiian coasts, wave interactions in the deep ocean near Hawaii, and storms far from Hawaii contribute energy to the seismic and acoustic spectra below 0.4 Hz. Wavefield directionality strongly influences the acoustic spectrum at frequencies below about 2 Hz, above which the acoustic levels imply near-isotropic surface wave directionality.Funding for the ALOHA Cabled Observatory was provided by the National Science Foundation and the State of Hawaii through the School of Ocean and Earth Sciences and Technology at the University of Hawaii-Manoa (F. Duennebier, PI). Donations from AT&T and TYCOM and the cooperation of the U.S. Navy made this project possible. The WHOI-Hawaii Ocean Time series Station (WHOTS) mooring is maintained by Woods Hole Oceanographic Institution (PIs R. Weller and A. Plueddemann) with funding from the NOAA Climate Program Office/Climate Observation Division. NSF grant OCE- 0926766 supported R. Lukas (co-PI) to augment and collaborate on the maintenance of WHOTS. Lukas was also supported during this analysis by The National Ocean Partnership Program “Advanced Coupled Atmosphere-Wave-Ocean Modeling for Improving Tropical Cyclone Prediction Models” under contract N00014-10-1-0154 to the University of Rhode Island (I. Ginis, PI).2012-09-1

Identification and genotyping of bacteria from paired vaginal and rectal samples from pregnant women indicates similarity between vaginal and rectal microflora

Background: The vaginal microflora is important for maintaining vaginal health and preventing infections of the reproductive tract. The rectum has been suggested as the major source for the colonisation of the vaginal econiche. Methods: To establish whether the rectum can serve as a possible bacterial reservoir for colonisation of the vaginal econiche, we cultured vaginal and rectal specimens from pregnant women at 35-37 weeks of gestation, identified the isolates to the species level with tRNA intergenic length polymorphism analysis (tDNA-PCR) and genotyped the isolates for those subjects from which the same species was isolated simultaneously vaginally and rectally, by RAPD-analysis. One vaginal and one rectal swab were collected from a total of each of 132 pregnant women at 35-37 weeks of gestation. Swabs were cultured on Columbia CNA agar and MRS agar. For each subject 4 colonies were selected for each of both sites, i.e. 8 colonies in total. Results: Among the 844 isolates that could be identified by tDNA-PCR, a total of 63 bacterial species were present, 9 (14%) only vaginally, 26 (41%) only rectally, and 28 (44%) in both vagina and rectum. A total of 121 (91.6%) of 132 vaginal samples and 51 (38.6%) of 132 rectal samples were positive for lactobacilli. L. crispatus was the most frequently isolated Lactobacillus species from the vagina (40% of the subjects were positive), followed by L. jensenii (32%), L. gasseri (30%) and L. iners (11%). L. gasseri was the most frequently isolated Lactobacillus species from the rectum (15%), followed by L. jensenii (12%), L. crispatus (11%) and L. iners (2%). A total of 47 pregnant women carried the same species vaginally and rectally. This resulted in 50 vaginal/rectal pairs of the same species, for a total of eight different species. For 34 of the 50 species pairs (68%), isolates with the same genotype were present vaginally and rectally and a high level of genotypic diversity within species per subject was also established. Conclusion: It can be concluded that there is a certain degree of correspondence between the vaginal and rectal microflora, not only with regard to species composition but also with regard to strain identity between vaginal and rectal isolates. These results support the hypothesis that the rectal microflora serves as a reservoir for colonisation of the vaginal econiche

Distinct Neurobehavioural Effects of Cannabidiol in Transmembrane Domain Neuregulin 1 Mutant Mice

The cannabis constituent cannabidiol (CBD) possesses anxiolytic and antipsychotic properties. We have previously shown that transmembrane domain neuregulin 1 mutant (Nrg1 TM HET) mice display altered neurobehavioural responses to the main psychoactive constituent of cannabis, Δ9-tetrahydrocannabinol. Here we investigated whether Nrg1 TM HET mice respond differently to CBD and whether CBD reverses schizophrenia-related phenotypes expressed by these mice. Adult male Nrg1 TM HET and wild type-like littermates (WT) received vehicle or CBD (1, 50 or 100 mg/kg i.p.) for 21 days. During treatment and 48 h after withdrawal we measured behaviour, whole blood CBD concentrations and autoradiographic receptor binding. Nrg1 HET mice displayed locomotor hyperactivity, PPI deficits and reduced 5-HT2A receptor binding density in the substantia nigra, but these phenotypes were not reversed by CBD. However, long-term CBD (50 and 100 mg/kg) selectively enhanced social interaction in Nrg1 TM HET mice. Furthermore, acute CBD (100 mg/kg) selectively increased PPI in Nrg1 TM HET mice, although tolerance to this effect was manifest upon repeated CBD administration. Long-term CBD (50 mg/kg) also selectively increased GABAA receptor binding in the granular retrosplenial cortex in Nrg1 TM HET mice and reduced 5-HT2A binding in the substantia nigra in WT mice. Nrg1 appears necessary for CBD-induced anxiolysis since only WT mice developed decreased anxiety-related behaviour with repeated CBD treatment. Altered pharmacokinetics in mutant mice could not explain our findings since no genotype differences existed in CBD blood concentrations. Here we demonstrate that Nrg1 modulates acute and long-term neurobehavioural effects of CBD, which does not reverse the schizophrenia-relevant phenotypes

Immunocompetent 3D Model of Human Upper Airway for Disease Modeling and In Vitro Drug Evaluation

The development of more complex in vitro models for the assessment of novel drugs and chemicals is needed because of the limited biological relevance of animal models to humans as well as ethical considerations. Although some human-cell-based assays exist, they are usually 2D, consist of single cell type, and have limited cellular and functional representation of the native tissue. In this study, we have used biomimetic porous electrospun scaffolds to develop an immunocompetent 3D model of the human respiratory tract comprised of three key cell types present in upper airway epithelium. The three cell types, namely, epithelial cells (providing a physical barrier), fibroblasts (extracellular matrix production), and dendritic cells (immune sensing), were initially grown on individual scaffolds and then assembled into the 3D multicell tissue model. The epithelial layer was cultured at the air–liquid interface for up to four weeks, leading to formation of a functional barrier as evidenced by an increase in transepithelial electrical resistance (TEER) and tight junction formation. The response of epithelial cells to allergen exposure was monitored by quantifying changes in TEER readings and by assessment of cellular tight junctions using immunostaining. It was found that epithelial cells cocultured with fibroblasts formed a functional epithelial barrier at a quicker rate than single cultures of epithelial cells and that the recovery from allergen exposure was also more rapid. Also, our data show that dendritic cells within this model remain viable and responsive to external stimulation as evidenced by their migration within the 3D construct in response to allergen challenge. This model provides an easy to assemble and physiologically relevant 3D model of human airway epithelium that can be used for studies aiming at better understanding lung biology, the cross-talk between immune cells, and airborne allergens and pathogens as well as drug delivery