Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Infection-Induced Peroxisome Biogenesis Is a Metabolic Strategy for Herpesvirus Replication.

Viral proteins have evolved to target cellular organelles and usurp their functions for virus replication. Despite the knowledge of these critical functions for several organelles, little is known about peroxisomes during infection. Peroxisomes are primarily metabolic organelles with important functions in lipid metabolism. Here, we discovered that the enveloped viruses human cytomegalovirus (HCMV) and herpes simplex virus type 1 (HSV-1) induce the biogenesis of and unique morphological changes to peroxisomes to support their replication. Targeted proteomic quantification revealed a global virus-induced upregulation of peroxisomal proteins. Mathematical modeling and microscopy structural analysis show that infection triggers peroxisome growth and fission, leading to increased peroxisome numbers and irregular disc-like structures. HCMV-induced peroxisome biogenesis increased the phospholipid plasmalogen, thereby enhancing virus production. Peroxisome regulation and dependence were not observed for the non-enveloped adenovirus. Our findings uncover a role of peroxisomes in viral pathogenesis, with likely implications for multiple enveloped viruses

Predicting Adolescent Electronic Cigarette Use: Differences by Never, Ever, and Current Users

OBJECTIVE: Rising rates of adolescent electronic cigarette (ECIG) use is concerning because it can lead to adverse health outcomes and increased risk behavior. There are known predictors of ever versus never ECIG use, but less are known about risk factors for ever versus current use of ECIGs. Problem behavior theory (PBT) was used to evaluate possible risk factors for different ECIG use status. METHODS: Participants were 573 high school students who completed questionnaires measuring ECIG use, as well as constructs within the Social Environment, Perceived Environment, Personality, and Behavior domains of PBT. Multinomial logistic regression was used to evaluate how predictor variables differentiated between participants who reported (a) never use, (b) ever ECIG use, or (c) current ECIG use. RESULTS: Adolescents were more likely to endorse ever ECIG use than never use if they reported peer ECIG use, perceived more benefits and fewer costs (e.g., health) of ECIG use, higher extraversion, alcohol and cigarette use (never vs. ever vs. past 30 days), or attended a school with a higher percentage of socioeconomically disadvantaged students. Adolescents were more likely to report current ECIG use than ever ECIG use if they perceived fewer costs of ECIG use or used cannabis in their lifetime (yes/no). CONCLUSIONS: PBT variables differentiated between ever ECIG use and never ECIG use. However, these variables did not differentiate between ever and current ECIG use. Identifying unique risk factors for current versus ever ECIG use is important to understanding persistent ECIG use and subsequent targeted prevention and intervention programs

Predicting Adolescent Electronic Cigarette Use: Differences by Never, Ever, and Current Users

Objective: Rising rates of adolescent electronic cigarette (ECIG) use is concerning because it can lead to adverse health outcomes and increased risk behavior. There are known predictors of ever versus never ECIG use, but less are known about risk factors for ever versus current use of ECIGs. Problem behavior theory (PBT) was used to evaluate possible risk factors for different ECIG use status. Methods: Participants were 573 high school students who completed questionnaires measuring ECIG use, as well as constructs within the Social Environment, Perceived Environment, Personality, and Behavior domains of PBT. Multinomial logistic regression was used to evaluate how predictor variables differentiated between participants who reported (a) never use, (b) ever ECIG use, or (c) current ECIG use. Results: Adolescents were more likely to endorse ever ECIG use than never use if they reported peer ECIG use, perceived more benefits and fewer costs (e.g., health) of ECIG use, higher extraversion, alcohol and cigarette use (never vs. ever vs. past 30 days), or attended a school with a higher percentage of socioeconomically disadvantaged students. Adolescents were more likely to report current ECIG use than ever ECIG use if they perceived fewer costs of ECIG use or used cannabis in their lifetime (yes/no). Conclusions: PBT variables differentiated between ever ECIG use and never ECIG use. However, these variables did not differentiate between ever and current ECIG use. Identifying unique risk factors for current versus ever ECIG use is important to understanding persistent ECIG use and subsequent targeted prevention and intervention programs

Repetitive head impacts do not affect postural control following a competitive athletic season

Evidence suggests that Repetitive Head Impacts (RHI) directly influence the brain over the course of a single contact collision season yet do not significantly impact a player\u27s performance on the standard clinical concussion assessment battery. The purpose of this study was to investigate changes in static postural control after a season of RHI in Division I football athletes using more sensitive measures of postural control as compared to a non-head contact sports. Fourteen Division I football players (CON) (age = 20.4 ± 1.12 years) and fourteen non-contact athletes (NON) (2 male, 11 female; age = 19.85 ± 1.21 years) completed a single trial of two minutes of eyes open quiet upright stance on a force platform (1000 Hz) prior to athletic participation (PRE) and at the end of the athletic season (POST). All CON athletes wore helmets outfitted with Head Impact Telemetry (HIT) sensors and total number of RHI and linear accelerations forces of each RHI were recorded. Center of pressure root mean square (RMS), peak excursion velocity (PEV), and sample entropy (SampEn) in the anteroposterior (AP) and mediolateral (ML) directions were calculated. CON group experienced 649.5 ± 496.8 mean number of impacts, 27.1 ± 3.0 mean linear accelerations, with ≈ 1% of total player impacts exceeded 98 g over the course of the season. There were no significant interactions for group x time RMS in the AP (p = 0.434) and ML (p = 0.114) directions, PEV in the AP (p = 0.262) and ML (p = 0.977) directions, and SampEn in the AP (p = 0.499) and ML (p = 0.984) directions. In addition, no significant interactions for group were observed for RMS in the AP (p = 0.105) and ML (p = 0.272) directions, PEV in the AP (p = 0.081) and ML (p = 0.143) directions, and SampEn in the AP (p = 0.583) and ML (p = 0.129) directions. These results suggest that over the course of a single competitive season, RHI do not negatively impact postural control even when measured with sensitive non-linear metrics