bluuebunny/crossref_metadata_2025 huggingface dataset:
OIP5-AS1 specifies p53-driven POX transcription regulated by TRPC6 in glioma
Authors: Shao Wei , Hao Zhen-Yu , Chen Yi-Fei , Du Jun , He Qian , Ren Liang-Liang , Gao Yan , Song Nan , Song Yan , He Hua , Wang Yi-Zheng
Published: January 2021

Transcription factors (TFs) control an array of expressed genes. However, the specifics of how a gene is expressed in time and space as controlled by a TF remain largely unknown. Here, in TRPC6-regulated proline oxidase 1 (POX) transcription in human glioma, we report that OIP5-AS1, a long noncoding RNA, determines the specificity of p53-driven POX expression. The OIP5-AS1/p53 complex via its 24 nucleotides binds to the POX promoter and is necessary for POX expression but not for p21 transcription. An O-site in the POX promoter to which OIP5-AS1 binds was identified that is required for OIP5-AS1/p53 binding and POX transcription. Blocking OIP5-AS1 binding to the O-site inhibits POX transcription and promotes glioma development. Thus, the OIP5-AS1/O-site module decides p53-controlled POX expression as regulated by TRPC6 and affects glioma development.
A celestial matryoshka: dynamical and spectroscopic analysis of the Albireo system
Authors: Drimmel Ronald , Sozzetti Alessandro , Schröder Klaus-Peter , Bastian Ulrich , Pinamonti Matteo , Jack Dennis , Hernández Huerta Missael A
Published: January 2021

We present a spectroscopic characterization and a new orbital solution for the binary system  β Cyg Aa/Ac (MCA 55), the primary component ( β Cyg A) of the well-known wide double star Albireo. By matching evolutionary tracks to the physical parameters of all three Albireo stars ( β Cyg Aa, Ac, and B) as obtained from a spectroscopic analysis of TIGRE and IUE spectra, we confirm that they are likely coeval. Our final orbit solution is based on radial-velocity measurements taken over a baseline exceeding 120 yr, combined with relative astrometry from speckle interferometric observations and the absolute astrometry from the Hipparcos and Gaia missions. Our final orbit solution has a period of 121.65$^{+3.34}_{-2.90}$ yr with an eccentricity of 0.20$^{+0.01}_{-0.02}$. Thanks to the inclusion of the absolute astrometry, we find a mass ratio of $q = 1.25^{+0.19}_{-0.17}$, and a total mass of $9.47_{-3.24}^{+5.88}$ M⊙, indicating that the secondary (Ac) is the more massive of the pair. These results strongly suggest the presence of a fourth, unseen, member of the Albireo system. Given the current photometric data, it is likely that  β Cyg A is itself a hierarchical triple. We also derive the systemic proper motion, line-of-sight velocity, and an orbital parallax of the  β Cyg A system, allowing us to quantitatively assess the hypothesis that Albireo A and B form a physically bound and genealogically connected system. Finally, we find four potential members of a common proper motion group with Albireo, though none anywhere as close by as the Albireo components A to B.
Radiative mixing layers: insights from turbulent combustion
Authors: Tan Brent , Oh S Peng , Gronke Max
Published: January 2021

Radiative mixing layers arise wherever multiphase gas, shear, and radiative cooling are present. Simulations show that in steady state, thermal advection from the hot phase balances radiative cooling. However, many features are puzzling. For instance, hot gas entrainment appears to be numerically converged despite the scale-free, fractal structure of such fronts being unresolved. Additionally, the hot gas heat flux has a characteristic velocity vin ≈ cs, cold(tcool/tsc, cold)−1/4 whose strength and scaling are not intuitive. We revisit these issues in 1D and 3D hydrodynamic simulations. We find that over-cooling only happens if numerical diffusion dominates thermal transport; convergence is still possible even when the Field length is unresolved. A deeper physical understanding of radiative fronts can be obtained by exploiting parallels between mixing layers and turbulent combustion, which has well-developed theory and abundant experimental data. A key parameter is the Damköhler number Da = τturb/tcool, the ratio of the outer eddy turnover time to the cooling time. Once Da > 1, the front fragments into a multiphase medium. Just as for scalar mixing, the eddy turnover time sets the mixing rate, independent of small scale diffusion. For this reason, thermal conduction often has limited impact. We show that vin and the effective emissivity can be understood in detail by adapting combustion theory scalings. Mean density and temperature profiles can also be reproduced remarkably well by mixing length theory. These results have implications for the structure and survival of cold gas in many settings, and resolution requirements for large scale galaxy simulations.
PHANGS–HST: star cluster spectral energy distribution fitting with cigale
Authors: Turner Jordan A , Dale Daniel A , Lee Janice C , Boquien Médéric , Chandar Rupali , Deger Sinan , Larson Kirsten L , Mok Angus , Thilker David A , Ubeda Leonardo , Whitmore Bradley C , Belfiore Francesco , Bigiel Frank , Blanc Guillermo A , Emsellem Eric , Grasha Kathryn , Groves Brent , Klessen Ralf S , Kreckel Kathryn , Kruijssen J M Diederik , Leroy Adam K , Rosolowsky Erik , Sanchez-Blazquez Patricia , Schinnerer Eva , Schruba Andreas , Van Dyk Schuyler D , Williams Thomas G
Published: January 2021

The sensitivity and angular resolution of photometric surveys executed by the Hubble Space Telescope (HST) enable studies of individual star clusters in galaxies out to a few tens of megaparsecs. The fitting of spectral energy distributions (SEDs) of star clusters is essential for measuring their physical properties and studying their evolution. We report on the use of the publicly available Code Investigating GALaxy Emission (cigale) SED fitting package to derive ages, stellar masses, and reddenings for star clusters identified in the Physics at High Angular resolution in Nearby GalaxieS–HST (PHANGS–HST) survey. Using samples of star clusters in the galaxy NGC 3351, we present results of benchmark analyses performed to validate the code and a comparison to SED fitting results from the Legacy Extragalactic Ultraviolet Survey. We consider procedures for the PHANGS–HST SED fitting pipeline, e.g. the choice of single stellar population models, the treatment of nebular emission and dust, and the use of fluxes versus magnitudes for the SED fitting. We report on the properties of clusters in NGC 3351 and find, on average, the clusters residing in the inner star-forming ring of NGC 3351 are young (<10 Myr) and massive (105 M⊙) while clusters in the stellar bulge are significantly older. Cluster mass function fits yield β values around −2, consistent with prior results with a tendency to be shallower at the youngest ages. Finally, we explore a Bayesian analysis with additional physically motivated priors for the distribution of ages and masses and analyse the resulting cluster distributions.
Atmospheric circulation of brown dwarfs and directly imaged exoplanets driven by cloud radiative feedback: effects of rotation
Authors: Tan Xianyu , Showman Adam P
Published: January 2021

Observations of brown dwarfs (BDs), free-floating planetary-mass objects, and directly imaged extrasolar giant planets (EGPs) exhibit rich evidence of large-scale weather. Cloud radiative feedback has been proposed as a potential mechanism driving the vigorous atmospheric circulation on BDs and directly imaged EGPs, and yet it has not been demonstrated in three-dimensional dynamical models at relevant conditions. Here, we present a series of atmospheric circulation models that self-consistently couple dynamics with idealized cloud formation and its radiative effects. We demonstrate that vigorous atmospheric circulation can be triggered and self-maintained by cloud radiative feedback. Typical isobaric temperature variation could reach over 100 K and horizontally averaged wind speed could be several hundreds of $\, {\rm m\, s^{-1}}$. The circulation is dominated by cloud-forming and clear-sky vortices that evolve over time-scales from several to tens of hours. The typical horizontal length-scale of dominant vortices is closed to the Rossby deformation radius, showing a linear dependence on the inverse of rotation rate. Stronger rotation tends to weaken vertical transport of vapour and clouds, leading to overall thinner clouds. Domain-mean outgoing radiative flux exhibits variability over time-scales of tens of hours due to the statistical evolution of storms. Different bottom boundary conditions in the models could lead to qualitatively different circulation near the observable layer. The circulation driven by cloud radiative feedback represents a robust mechanism generating significant surface inhomogeneity as well as irregular flux time variability. Our results have important implications for near-infrared (IR) colours of dusty BDs and EGPs, including the scatter in the near-IR colour–magnitude diagram and the viewing-geometry-dependent near-IR colours.
Modelling population III stars for seminumerical simulations
Authors: Tanaka Toshiyuki , Hasegawa Kenji
Published: January 2021

Theoretically modelling the 21-cm signals caused by Population III stars (Pop III stars) is the key to extracting fruitful information on Pop III stars from current and forthcoming 21-cm observations. In this work, we develop a new module of Pop III stars in which the escape fractions of ionizing photons and Lyman–Werner (LW) photons, photoheating by UV radiation, and LW feedback are consistently incorporated. By implementing the module into a public 21-cm seminumerical simulation code, 21cmfast, we demonstrate 21-cm signal calculations, neglecting X-ray heating and focusing on the high redshifts when we assume that the formation of Pop III stars dominates that of other populations. What we find is that the contribution from Pop III stars to cosmic reionization significantly depends on the treatment of the escape fraction. With our escape fraction model, Pop III stars hardly contribute to reionization because less massive haloes, whose escape fraction are high, cannot host Pop III stars due to LW feedback. On the other hand, massive minihaloes contribute to reionization with the conventional constant escape fraction. We also find that UV photoheating has non-negligible impact on the 21-cm global signal and the 21-cm power spectrum if the ionization fraction of the Universe is higher than roughly 1 per cent. In this case, the strength of the 21-cm global signal depends on the photoheating efficiency and thus on the Pop III star mass. We conclude that detailed modelling of Pop III stars is imperative to predict 21-cm observables accurately for future observations.
A genome-wide strategy to identify causes and consequences of retrotransposon expression finds activation by BRCA1 in ovarian cancer
Authors: Alkailani Maisa , Palidwor Gareth , Poulin Ariane , Mohan Raghav , Pepin David , Vanderhyden Barbara , Gibbings Derrick
Published: January 2021

It is challenging to identify the causes and consequences of retrotransposon expression in human disease due to the hundreds of active genomic copies and their poor conservation across species. We profiled genomic insertions of retrotransposons in ovarian cancer. In addition, in ovarian and breast cancer we analyzed RNAs exhibiting Bayesian correlation with retrotransposon RNA to identify causes and consequences of retrotransposon expression. This strategy finds divergent inflammatory responses associated with retrotransposon expression in ovarian and breast cancer and identifies new factors inducing expression of endogenous retrotransposons including anti-viral responses and the common tumor suppressor BRCA1. In cell lines, mouse ovarian epithelial cells and patient-derived tumor spheroids, BRCA1 promotes accumulation of retrotransposon RNA. BRCA1 promotes transcription of active families of retrotransposons and their insertion into the genome. Intriguingly, elevated retrotransposon expression predicts survival in ovarian cancer patients. Retrotransposons are part of a complex regulatory network in ovarian cancer including BRCA1 that contributes to patient survival. The described strategy can be used to identify the regulators and impacts of retrotransposons in various contexts of biology and disease in humans.
Water transport to the core–mantle boundary
Authors: Walter Michael J
Published: January 2021

Water is transported to Earth's interior in lithospheric slabs at subduction zones. Shallow dehydration fuels hydrous island arc magmatism but some water is transported deeper in cool slab mantle. Further dehydration at ∼700 km may limit deeper transport but hydrated phases in slab crust have considerable capacity for transporting water to the core-mantle boundary. Quantifying how much remains the challenge.
Meta-analysis of Clinical Outcomes Using Ceftazidime/Avibactam, Ceftolozane/Tazobactam, and Meropenem/Vaborbactam for the Treatment of Multidrug-Resistant Gram-Negative Infections
Authors: Wilson Geneva M , Fitzpatrick Margaret , Walding Kyle , Gonzalez Beverly , Schweizer Marin L , Suda Katie J , Evans Charlesnika T
Published: January 2021

Ceftolozane-tazobactam (C/T), ceftazidime-avibactam (C/A), and meropenem/vaborbactam (M/V) are new beta-lactam/beta-lactamase combination antibiotics commonly used to treat multidrug-resistant Pseudomonas aeruginosa (MDRPA) and carbapenem-resistant Enterobacteriaceae (CRE) infections. This review reports the clinical success rates for C/T, C/A, and M/V. PubMed and EMBASE were searched from January 1, 2012, through September 2, 2020, for publications detailing the use of C/T, C/A, and M/V. A meta-analysis determined the pooled effectiveness of C/T, C/A, and M/V. The literature search returned 1950 publications; 29 publications representing 1620 patients were retained. Pneumonia was the predominant infection type (49.8%). MDRPA was the major pathogen treated (65.3%). The pooled clinical success rate was 73.3% (95% CI, 68.9%–77.5%). C/T, C/A, or M/V resistance was reported in 8.9% of the population. These antibiotics had a high clinical success rate in patients with complicated infections and limited treatment options. Larger studies comparing C/T, C/A, and M/V against other antibiotic regimens are needed.
SARS-CoV-2 Seroconversion and Viral Clearance in Patients Hospitalized With COVID-19: Viral Load Predicts Antibody Response
Authors: Masiá Mar , Telenti Guillermo , Fernández Marta , García José A , Agulló Vanesa , Padilla Sergio , García-Abellán Javier , Guillén Lucía , Mascarell Paula , Asenjo José C , Gutiérrez Félix
Published: January 2021

Background

The interdependencies of viral replication and the host immune response in patients with coronavirus disease 2019 (COVID-19) remain to be defined. We investigated the viral determinants of antibody response, the predictors of nonseroconversion, and the role of antibodies on viral dynamics.

Methods

This was a prospective study in patients hospitalized with COVID-19 that was microbiologically confirmed by real-time polymerase chain reaction (RT-PCR). Serial nasopharyngeal and oropharyngeal swabs and plasma samples were obtained for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies (total and S-IgG/N-IgG), respectively.

Results

Of 132 patients included, 99 (75%) showed positive antibody titers after a median (Q1–Q3) of 11 (8–14) days. The median (Q1–Q3) follow-up was 74.5 (63.0–87.0) days. In an adjusted linear regression model, time to seropositivity was inversely associated with peak log SARS-CoV-2 viral load (P = .009) and positively with time to viral clearance (P = .004). Adjusted predictors of S-IgG levels were time to viral clearance (P < .001), bilateral lung infiltrates on admission (P = .011), and the time-dependent SARS-CoV-2 RNA (P < .001) and SARS-CoV-2 RNA area under the curve (P = .001). Thirty-three (25%) patients showed undetectable antibody titers. Patients who did not seroconvert had higher cycle threshold values of RT-PCR (38.0 vs 28.0; P < .001), had shorter time to viral clearance (3.0 vs 41.0; P < .001), and were more likely to have SARS-CoV-2 only detected on fecal samples (P < .001). Nonseroconvertors had also lower levels of blood inflammatory biomarkers on admission and lower disease severity.

Conclusions

Viral replication determines the magnitude of antibody response to SARS-CoV-2, which, in turn, contributes to viral clearance. COVID-19 patients who do not seroconvert exhibit a differential virological and clinical profile.
Direct-Acting Antiviral Treatment for Hepatitis C Genotypes Uncommon in High-Income Countries: A Dutch Nationwide Cohort Study
Authors: Isfordink Cas J , van de Laar Thijs J W , Rebers Sjoerd P H , Wessels Els , Molenkamp Richard , Knoester Marjolein , Baak Bert C , van Nieuwkoop Cees , van Hoek Bart , Brakenhoff Sylvia M , Blokzijl Hans , Arends Joop E , van der Valk Marc , Schinkel Janke ,   HepNed Study Group, Willemse Sophie , Erken Robin , Bomers Marije , Ramsoekh Dewkoemar , Amsterdam U M C , de Knegt Rob , de Man Rob , Rijnders Bart , Erasmus M C , van Soest Hanneke , Haaglanden M C , Koek Ger , Posthouwer Dirk , Koc Ozgür , Maastricht U M C , Burger David , van Dijk Marleen , Drenth Joost , von den Hoff Daan , Radboud U M C , Brouwer Johannes , de Graaf Gasthuis Reinier , Boland Greet , van Erpecum Karel , Utrecht U M C
Published: January 2021

Background

The majority of hepatitis C virus (HCV) infections are found in low- and middle-income countries, which harbor many region-specific HCV subtypes. Nevertheless, direct-acting antiviral (DAA) trials have almost exclusively been conducted in high-income countries, where mainly epidemically spread HCV subtypes are present. Recently, several studies have demonstrated suboptimal DAA efficacy for certain nonepidemic subtypes, which could hamper global HCV elimination. Therefore, we aimed to evaluate DAA efficacy in patients treated for a nonepidemic HCV genotype infection in the Netherlands.

Methods

We performed a nationwide retrospective study including patients treated with interferon-free DAAs for an HCV genotype other than 1a/1b/2a/2b/3a/4a/4d. The genotype was determined by NS5B region phylogenetic analysis. The primary end point was SVR-12. If stored samples were available, NS5A and NS5B sequences were obtained for resistance-associated substitutions (RAS) evaluation.

Results

We included 160 patients, mainly infected with nonepidemic genotype 2 (41%) and 4 (31%) subtypes. Most patients were from Africa (45%) or South America (24%); 51 (32%) were cirrhotic. SVR-12 was achieved in 92% (140/152) of patients with available SVR-12 data. Only 73% (8/11) genotype 3–infected patients achieved SVR-12, the majority being genotype 3b patients with 63% (5/8) SVR. Regardless of SVR, all genotype 3b patients had 30K and 31M RAS.

Conclusions

The DAA efficacy we observed in most nonepidemic genotypes in the Netherlands seems reassuring. However, the low SVR-12 rate in subtype 3b infections is alarming, especially as it is common in several HCV-endemic countries. Alongside earlier results, our results indicate that a remaining challenge for global HCV elimination is confirming and monitoring DAA efficacy in nonepidemic genotypes.
The Clinical Course of COVID-19 in the Outpatient Setting: A Prospective Cohort Study
Authors: Blair Paul W , Brown Diane M , Jang Minyoung , Antar Annukka A R , Keruly Jeanne C , Bachu Vismaya S , Townsend Jennifer L , Tornheim Jeffrey A , Keller Sara C , Sauer Lauren , Thomas David L , Manabe Yukari C ,   Ambulatory COVID Study Team, Cox Andrea L , Heaney Chris D , Klein Sabra L , Mehta Shruti H , Mostafa Heba , Pekosz Andy S , Pisanic Nora , Smith L Leigh , Armstrong Derek T , Azamfirei Razvan , Barnaba Brittany , Charles Curtisha , Church Taylor , Dai Weiwei , Fuchs Joelle , Ganesan Abhinaya , Hardick Justin , Holden Jeffrey , Johnstone Jaylynn R , Kruczynski Kate , Kusemiju Oyinkansola , Lambrou Anastasia , Li Lucy , Littlefield Kirsten , Montana Manuela Plazas , Park Han-Sol , Payton Christine B , Popper Caroline , Prizzi Michelle , Reuland Carolyn J , Sewell Thelio , Tuchler Amanda , Ursin Rebecca L , Walch Samantha N
Published: January 2021

Background

Outpatient coronavirus disease 2019 (COVID-19) has been insufficiently characterized. To determine the progression of disease and determinants of hospitalization, we conducted a prospective cohort study.

Methods

Outpatient adults with positive reverse transcription polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited by phone between April 21 and July 23, 2020, after receiving outpatient or emergency department testing within a large health network in Maryland, United States. Symptoms were collected by participants on days 0, 3, 7, 14, 21, and 28, and portable pulse oximeter oxygen saturation (SaO2), heart rate, and temperature were collected for 15 consecutive days. Baseline demographics, comorbid conditions, and vital signs were evaluated for risk of subsequent hospitalization using negative binomial and logistic regression.

Results

Among 118 SARS-CoV-2-infected outpatients, the median age (interquartile range [IQR]) was 56.0 (50.0–63.0) years, and 50 (42.4%) were male. Among individuals in the first week of illness (n = 61), the most common symptoms included weakness/fatigue (65.7%), cough (58.8%), headache (45.6%), chills (38.2%), and anosmia (27.9%). Participants returned to their usual health a median (IQR) of 20 (13–38) days from symptom onset, and 66.0% of respondents were at their usual health during the fourth week of illness. Over 28 days, 10.9% presented to the emergency department and 7.6% required hospitalization. The area under the receiver operating characteristics curve for the initial home SaO2 for predicting subsequent hospitalization was 0.86 (95% CI, 0.73–0.99).

Conclusions

Symptoms often persisted but uncommonly progressed to hospitalization among outpatients with COVID-19. Home SaO2 may be a helpful tool to stratify risk of hospitalization.
Sleep walking copepods? Calanus diapausing in hypoxic waters adjust their vertical position during winter
Authors: Kaartvedt Stein , Røstad Anders , Titelman Josefin
Published: January 2021

While hypoxia is generally associated with negative connotations, some animals may also take advantage of reduced oxygen concentrations. However, the dynamics of such processes for zooplankton are poorly understood. We made continuous acoustic studies of Calanus helgolandicus overwintering in hypoxic waters (Oslofjorden, Norway). Their apparent minimum oxygen tolerance was 0.2–0.3 mL O2 L−1 at 8°C. The copepods adjusted their vertical distribution in concert with the upward progression of hypoxia as oxygen contents declined in the course of winter. The hypoxic overwintering habitat largely excluded potential predators and mortality appeared low in early winter. As the copepod distribution shallowed in phase with declining oxygen contents at depth, mortality increased. In contrast to recent predictions, C. helgolandicus had sufficient energy reserves to sustain long-term overwintering. Termination of the overwintering phase in spring was gradual but appeared to accelerate during the development of the spring bloom. Enhanced oceanic deoxygenation with climate change may affect seasonally migrating copepods in unpredictable ways.
Beta interferons as immunotherapy in multiple sclerosis: a new outlook on a classic drug during the COVID-19 pandemic
Authors: Dumitrescu L , Papathanasiou A , Coclitu C , Constantinescu C S , Popescu B O , Tanasescu R
Published: January 2021

Beta interferons (IFN-β) are pleiotropic cytokines with antiviral properties. They play important roles in the pathogenesis of multiple sclerosis (MS), an incurable immune-mediated disorder of the central nervous system. The clinical expression of MS is heterogeneous, with relapses of neuroinflammation and with disability accrual in considerable part unrelated to the attacks. The injectable recombinant IFN-β preparations are the first approved disease-modifying treatments for MS. They have moderate efficacy in reducing the frequency of relapses, but good long-term cost-efficacy and safety profiles, so are still widely used. They have some tolerability and adherence issues, partly mitigated in recent years by the introduction of a PEGylated formulation and use of ‘smart’ autoinjector devices. Their general impact on long-term disability is modest but could be further improved by developing accurate tools for identifying the patient profile of best responders to IFN-β. Here, we present the IFN-β-based immunomodulatory therapeutic approaches in MS, highlighting their place in the current coronavirus disease (COVID-19) pandemic. The potential role of IFN-β in the treatment of COVID-19 is also briefly discussed.
Methamphetamine and sleep impairments: neurobehavioral correlates and molecular mechanisms
Authors: Vrajová Monika , Šlamberová Romana , Hoschl Cyril , Ovsepian Saak V
Published: January 2021

Methamphetamine is a potent and highly addictive psychostimulant, and one of the most widely used illicit drugs. Over recent years, its global usage and seizure have been on a rapid rise, with growing detrimental effects on mental and physical health, and devastating psychosocial impact pressing for intervention. Among the unwanted effects of methamphetamine, acute and long-term sleep impairments are of major concern, posing a significant therapeutic challenge, and a cause of addiction relapse. Unraveling mechanisms and functional correlates of methamphetamine-related sleep and circadian disruption are, therefore, of key relevance to translational and clinical psychiatry. In this article, we review the mounting evidence for the acute and long-term impairements of sleep–wake behavior and circadian activity caused by single or recurring methamphetamine usage and withdrawal. Factors contributing to the severity of sleep loss and related cognitive deficit, with risks of relapse are discussed. Key molecular players mediating methamphetamine-induced dopamine release and neuromodulation are considered, with wake-promoting effects in mesolimbic circuits. The effects on various sleep phases and related changes in dopamine levels in selected subcortical structures are reviewed and compared to other psychostimulants with similar action mechanisms. A critical appraisal is presented of the therapeutic use of modafinil, countering sleep, and circadian rhythm impairments. Finally, emerging knowledge gaps and methodical limitations are highlighted along with the areas for future research and therapeutic translation.
Association of objectively measured sleep with frailty and 5-year mortality in community-dwelling older adults
Authors: Guida Jennifer L , Alfini Alfonso J , Gallicchio Lisa , Spira Adam P , Caporaso Neil E , Green Paige A
Published: January 2021

Study Objectives

To determine whether actigraphy-measured sleep was independently associated with risk of frailty and mortality over a 5-year period among older adults.

Methods

We used data from Waves 2 (W2) and 3 (W3) (2010–2015) of the National Social Life, Health and Aging Project, a prospective cohort of community-dwelling older adults born between 1920 and 1947. One-third of W2 respondents were randomly selected to participate in a sleep study, of whom N = 727 consented and N = 615 were included in the analytic sample. Participants were instructed to wear a wrist actigraph for 72 h (2.93 ± 0.01 nights). Actigraphic sleep parameters were averaged across nights and included total sleep time, percent sleep, sleep fragmentation index, and wake after sleep onset. Subjective sleep was collected via questionnaire. Frailty was assessed using modified Fried Frailty Index. Vital status was ascertained at the time of the W3 interview. W3 frailty/mortality status was analyzed jointly with a four-level variable: robust, pre-frail, frail, and deceased. Associations were modeled per 10-unit increase.

Results

After controlling for baseline frailty (robust and pre-frail categories), age, sex, education, body mass index, and sleep time preference, a higher sleep fragmentation index was associated with frailty (OR = 1.70, 95% CI: 1.02–2.84) and mortality (OR = 2.12, 95% CI: 1.09–4.09). Greater wake after sleep onset (OR = 1.24, 95% CI: 1.02–1.50) and lower percent sleep (OR = 0.41, 95% CI: 0.17–0.97) were associated with mortality.

Conclusions

Among community-dwelling older adults, actigraphic sleep is associated with frailty and all-cause mortality over a 5-year period. Further investigation is warranted to elucidate the physiological mechanisms underlying these associations.
Identifying and characterizing longitudinal patterns of insomnia across the deployment cycle in active duty Army soldiers
Authors: Miller Katherine E , Ramsey Christine M , Boland Elaine M , Klingaman Elizabeth A , Gehrman Philip
Published: January 2021

Study Objectives

The present study characterized a sample of 4,667 Army soldiers based on their patterns of insomnia before, during, and after deployment, and explored pre-deployment factors predictive of these patterns.

Methods

Data were analyzed from the Army Study to Assess Risk and Resilience in Service members (STARRS)—Pre/Post Deployment Study (PPDS), using surveys that captured data approximately 1–2 months pre-deployment, and 3- and 9-month post-deployment from soldiers deployed to Afghanistan. Patterns of insomnia across time were examined. Theoretically derived variables linked to sleep disturbance were examined as predictors of the insomnia patterns.

Results

Five longitudinal patterns of insomnia characterized the majority of the sample: “No Insomnia” (no insomnia symptoms at any timepoint; 31%), “Deployment-related Insomnia” (no pre-deployment insomnia, developed insomnia symptoms during deployment and recovered; 40%), “Incident Insomnia” (development insomnia during or shortly after deployment that did not remit; 14%), “Chronic Insomnia” (insomnia both pre- and post-deployment; 11%), and “Other Insomnia” (reported insomnia at ≥1 timepoint, but no clear pattern across the deployment cycle; 4%). Several pre-deployment factors were predictive of insomnia trajectories, including lifetime major depressive episodes, traumatic brain injury history, posttraumatic stress disorder, and past year personal life stressors.

Conclusions

Distinct longitudinal patterns of insomnia were identified, with more than half of the sample reporting insomnia at some point in the deployment cycle. Identifying mental health conditions that are associated with different insomnia patterns prior to deployment can inform targeted interventions to reduce long-term sleep difficulty.
Implications of the COVID-19 pandemic in eliminating trachoma as a public health problem
Authors: Blumberg Seth , Borlase Anna , Prada Joaquin M , Solomon Anthony W , Emerson Paul , Hooper Pamela J , Deiner Michael S , Amoah Benjamin , Hollingsworth T Déirdre , Porco Travis C , Lietman Thomas M
Published: January 2021

Background

Progress towards elimination of trachoma as a public health problem has been substantial, but the coronavirus disease 2019 (COVID-19) pandemic has disrupted community-based control efforts.

Methods

We use a susceptible-infected model to estimate the impact of delayed distribution of azithromycin treatment on the prevalence of active trachoma.

Results

We identify three distinct scenarios for geographic districts depending on whether the basic reproduction number and the treatment-associated reproduction number are above or below a value of 1. We find that when the basic reproduction number is <1, no significant delays in disease control will be caused. However, when the basic reproduction number is >1, significant delays can occur. In most districts, 1 y of COVID-related delay can be mitigated by a single extra round of mass drug administration. However, supercritical districts require a new paradigm of infection control because the current strategies will not eliminate disease.

Conclusions

If the pandemic can motivate judicious, community-specific implementation of control strategies, global elimination of trachoma as a public health problem could be accelerated.
Prevalence and evaluation of risk factors of anti-retroviral therapy failure among human immunodeficiency virus/acquired immune deficiency syndrome patients in North India
Authors: Basu Ayan , Biswas Ashutosh , Wig Naveet , Sood Rita , Soneja Manish , Nischal Neeraj , Das Bimal Kumar
Published: January 2021

Background

The prevalence of anti-retroviral therapy (ART) failure is not uniform in India. In this study we attempted to determine the prevalence and risk factors of treatment failure among patients who were on ART for >1 y.

Methods

We conducted an ambispective study from 2017 to 2019 in the All India Institute of Medical Sciences, New Delhi, India. Patients and their past medical records were examined to determine clinical, immunological and virological failure.

Results

Among 301 enrolled patients, the majority was male (61.8%), with a mean age of 36.98±10.84 y. The prevalence of ART failure in our study was 10.63% (32/301). Clinical, immunological and virological failure rates were 1.66%, 10.63% and 5.65%, respectively. The maximum chance of failure was the tenofovir–lamivudine–nevirapine (33.3%) regimen followed by the stavudine–lamivudine–nevirapine (30.4%) regimen. Among the nucleoside reverse transcriptase inhibitors, a stavudine-based regimen had a significantly greater chance of failure (25.8%) compared with tenofovir (9.6%) and zidovudine (7.9%) regimens (p<0.005). Low baseline CD4 count and development of tuberculosis after ART initiation were significantly (p<0.05) associated with treatment failure in univariate analysis. Patients with a low peak CD4 count (adjusted odds ratio [AOR 4.26 {95% confidence interval  1.83 to 9.88}]) and who developed symptoms after ART initiation (AOR 3.77 [95% CI 1.47 to 9.69]) had significantly higher odds of treatment failure in the multivariate analysis (p<0.001).

Conclusions

Early identification of risk factors by regular follow-up and selection of the proper ART regimen can reduce the rate of treatment failure.
Experimental increase of worker diversity benefits brood production in ants
Authors: Psalti Marina N. , Gohlke Dustin , Libbrecht Romain
Published: January 2021

The reproductive division of labor of eusocial insects, whereby one or several queens monopolize reproduction, evolved in a context of high genetic relatedness. However, many extant eusocial species have developed strategies that decrease genetic relatedness in their colonies, suggesting some benefits of the increased diversity. Multiple studies support this hypothesis by showing positive correlations between genetic diversity and colony fitness, as well as finding effects of experimental manipulations of diversity on colony performance. However, alternative explanations could account for most of these reports, and the benefits of diversity on fitness in eusocial insects still await validation. In this study, we experimentally increased worker diversity in the antLasius nigerwhile controlling for typical confounding factors. We found that experimental colonies composed of workers coming from three different source colonies produced more larvae and showed more variation in size compared to groups of workers coming from a single colony. We propose that the benefits of increased diversity stemmed from an improved division of labor. Our study confirms that worker diversity enhances colony performance, thus providing a possible explanation for the evolution of multiply mated queens and multiple-queen colonies in many species of eusocial insects.
Chitinase 3-like-1 is a Therapeutic Target That Mediates the Effects of Aging in COVID-19
Authors: Kamle Suchitra , Ma Bing , He Chuan Hua , Akosman Bedia , Zhou Yang , Lee Chang Min , El-Deiry Wafik S. , Huntington Kelsey , Liang Olin , Machan Jason T. , Kang Min-Jong , Shin Hyeon Jun , Mizoguchi Emiko , Lee Chun Geun , Elias Jack A.
Published: January 2021

COVID-19 is caused by the SARS-CoV-2 (SC2) virus and is more prevalent and severe in the elderly and patients with comorbid diseases (CM). Because chitinase 3-like-1 (CHI3L1) is induced during aging and CM, the relationships between CHI3L1 and SC2 were investigated. Here we demonstrate that CHI3L1 is a potent stimulator of the SC2 receptor ACE2 and viral spike protein priming proteases (SPP), that ACE2 and SPP are induced during aging and that anti-CHI3L1, kasugamycin and inhibitors of phosphorylation, abrogate these ACE2- and SPP-inductive events. Human studies also demonstrated that the levels of circulating CHI3L1 are increased in the elderly and patients with CM where they correlate with COVID-19 severity. These studies demonstrate that CHI3L1 is a potent stimulator of ACE2 and SPP; that this induction is a major mechanism contributing to the effects of aging during SC2 infection and that CHI3L1 coopts the CHI3L1 axis to augment SC2 infection. CHI3L1 plays a critical role in the pathogenesis of and is an attractive therapeutic target in COVID-19.
A multi-dimensional integrative scoring framework for predicting functional variants in the human genome
Authors: Li Xihao , Yung Godwin , Zhou Hufeng , Sun Ryan , Li Zilin , Liu Yaowu , Ionita-Laza Iuliana , Lin Xihong
Published: January 2021

Attempts to identify and prioritize functional DNA elements in coding and noncoding regions, particularly through use of in silico functional annotation data,continue to increase in popularity. However, specific functional roles may vary widely from one variant to another, making it challenging to summarize different aspects of variant function. Here we propose Multi-dimensional Annotation Class Integrative Estimation (MACIE), an unsupervised multivariate mixed model framework capable of integrating annotations of diverse origin to assess multi-dimensional functional roles for both coding and noncoding variants. Unlike existing one-dimensional scoring methods, MACIE views variant functionality as a composite attribute encompassing multiple characteristics, and estimates the joint posterior functional probability vector of each genomic position, a quantity that offers richer and more interpretable information in the presence of multiple aspects of functionality. Applied to a variety of independent coding and non-coding datasets, MACIE demonstrates powerful and robust performance in discriminating between functional and non-functional variants. We also show an application of MACIE to fine-mapping using lipids GWAS summary statistics data from the European Network for Genetic and Genomic Epidemiology Consortium.
A guide to between-community functional dissimilarity measures
Authors: Lengyel Attila , Botta-Dukát Zoltán
Published: January 2021

One of the effective tools to study the variation between communities is the use of pairwise dissimilarity indices. Besides species as variables, the involvement of trait information provides valuable insight into the functioning of ecosystems. In recent years, a variety of indices have been proposed to quantify functional dissimilarity between communities. These indices follow different approaches to account for between-species similarities in calculating community dissimilarity, yet they all have been proposed as straightforward tools.

In this paper, we review the trait-based dissimilarity indices available in the literature and identify the most important conceptual and technical properties that differentiate among them and that must be considered before their application.

We identify two primary aspects that need to be considered before choosing a functional dissimilarity index. The first one is the way communities are represented in the trait space. The three main types of representations are the typical values, the combination of species×sites and species×trait matrices, and the hypervolumes. The second decision is the concept of dissimilarity to follow, including two options: distances and (lack of) overlaps. We use the above scheme to discuss the available functional dissimilarity indices and evaluate their relations to each other, their capabilities, and accessibility.
Decoding the single-cell landscape and intercellular crosstalk in the transplanted liver: a 4-dimension mouse model
Authors: Huang Haitao , Zhang Xueyou , Chen Hui , Feng Shi , Zhang Cheng , Chen Ruihan , Lin Yimou , Ji Qinghua , Ling Qi
Published: January 2021

Graft remodeling after transplantation maintains graft functionality and determines graft survival. However, a comprehensive understanding of cellular diversity and interplay during graft remodeling remains to be fully characterized. In this study, we established a well tolerant C57BL/6 to C57BL/6 orthotopic liver transplantation (LT) mice model and observed two stages of graft recovery including an acute phase and a steady phase. We next performed single-cell RNA sequencing (scRNA-seq) and cytometry by time-of-flight (CyTOF) and recorded the cellular hierarchy in the transplanted liver during the two stages. Besides the dynamic change of cell proportion, it was notable that recipient-derived cells took over the transplanted liver in most cell types (e.g., B cells, T cells, dendritic cells, granulocytes and monocytes) except CD206+MerTK+macrophages and CD161+CD49a+CD49b−natural killer cells. We then focused on macrophages and captured 5 distinct transcriptional signatures to define novel subclusters. Using a ligand-receptor interaction strategy, we identified specific macrophage-hepatocyte interactions during the acute and stable phases, causing metabolic remodeling in the transplanted liver. Our results delineated a 4-dimension cell atlas (type-proportion-source-time) of the transplanted liver, which sheds light on the physiological process of liver graft maintenance and graft-recipient crosstalk.
The role of water mobility in protein misfolding
Authors: Stephens Amberley D. , Kölbel Johanna , Moons Rani , Ruggerio Michael T. , Mahmoudi Najet , Shmool Talia A. , McCoy Thomas M. , Nietlispach Daniel , Routh Alexander F. , Sobott Frank , Zeitler J. Axel , Schierle Gabriele S. Kaminski
Published: January 2021

The propensity for intrinsically disordered proteins to aggregate is heavily influenced by their surrounding environment. Here, we show that the mobility of the surrounding water molecules directly influences the aggregation rate of α-synuclein (aSyn), a protein associated with Parkinson’s disease. We observe that the addition of NaCl reduces the mobility of water, while addition of CsI increases the mobility of water. In turn, this reduces and increases the mobility of aSyn, respectively, given the change in strength and lifetime of the intermolecular forces. The reduction of aSyn mobility in the presence of NaCl ions leads to increased aggregation rates, which may be due to aggregation-competent conformations being stable for longer, thereby increasing the likelihood of establishing interactions between two adjacent monomers. In contrast, aSyn is more mobile when CsI is dissolved in the aqueous phase which leads to a reduction of successful monomeric interactions. We thus highlight the importance of the surrounding environment and describe how ion content can influence water mobility and the misfolding rate of amyloidogenic proteins, such as aSyn. By modulating the cellular environment to increase water mobility or finding small molecules to increase protein dynamics, new therapeutic targets may be found.
Modulated termination of non-coding transcription partakes in the regulation of gene expression
Authors: Haidara Nouhou , Porrua Odil
Published: January 2021

Pervasive transcription is a universal phenomenon leading to the production of a plethora of non-coding RNAs. If left uncontrolled, pervasive transcription can be harmful for genome expression and stability. However, non-coding transcription can also play important regulatory roles, for instance by promoting the repression of specific genes by a mechanism of transcriptional interference. The efficiency of transcription termination can strongly influence the regulatory capacity of non-coding transcription events, yet very little is known about the mechanisms modulating the termination of non-coding transcription in response to environmental cues.

Here, we address this question by investigating the mechanisms that regulate the activity of the main actor in termination of non-coding transcription in budding yeast, the helicase Sen1. We identify a phosphorylation at a conserved threonine of the catalytic domain of Sen1 and we provide evidence that phosphorylation at this site reduces the efficiency of Sen1-mediated termination. Interestingly, we find that this phosphorylation impairs termination at an unannotated non-coding gene, thus repressing the expression of a downstream gene encoding the master regulator of Zn homeostasis, Zap1. Consequently, many additional genes exhibit an expression pattern mimicking conditions of Zn excess, whereZAP1is naturally repressed.

Our findings provide a novel paradigm of gene regulatory mechanism relying on the direct modulation of non-coding transcription termination.
In vivo deciduous dental eruption in LuiKotale bonobos and Gombe chimpanzees
Authors: Lee Sean M. , Sutherland L. J. , Fruth Barbara , Murray Carson M. , Lonsdorf Elizabeth V. , Arbenz-Smith Keely , Augusto Rafael , Brogan Sean , Canington Stephanie L. , Lee Kevin C. , McGrath Kate , McFarlin Shannon C. , Hohmann Gottfried
Published: January 2021

Existing data on bonobo and chimpanzee dental eruption timing are derived predominantly from captive individuals or deceased wild individuals. However, recent advances in noninvasive photographic monitoring of living, wild apes have greatly expanded our knowledge of chimpanzee dental eruption in relatively healthy individuals under naturalistic conditions. We employ similar methods to expand on this knowledge by reporting deciduous dental eruption ages in living, wild bonobos and chimpanzees from LuiKotale, Democratic Republic of the Congo and Gombe National Park, Tanzania, respectively. Deciduous dental eruption ages in our sample generally fall within the range of variation previously documented for captive chimpanzees. We also found substantial variation in deciduous canine eruption timing, particularly among bonobos. One bonobo had a deciduous canine present by 227 days old while another did not have a deciduous canine present at 477 days old. As more data accumulate from these populations, future studies should consider sources of variation in deciduous canine eruption timing and relationships with other aspects of life history.
Occupancy-collection models: Towards bias-corrected modeling of species’ distributions using unstructured occurrence data from museums and herbaria
Authors: Erickson Kelley D. , Smith Adam B.
Published: January 2021

The digitization of museum collections as well as an explosion in citizen science initiatives has resulted in a wealth of data that can be useful for understanding the global distribution of biodiversity, provided that the well-documented biases inherent in unstructured opportunistic data are accounted for. While traditionally used to model imperfect detection using structured data from systematic surveys of wildlife, occupancy-detection models provide a framework for modelling the imperfect collection process that results in digital specimen data. In this study, we explore methods for adapting occupancy-detection models for use with biased opportunistic occurrence data from museum specimens and citizen science platforms using 7 species of Anacardiaceae in Florida as a case study. We explored two methods of incorporating information about collection effort to inform our uncertainty around species presence: (1) filtering the data to exclude collectors unlikely to collect the focal species and (2) incorporating collection covariates (collection type and history of previous detections) into a model of collection probability. We found that the best models incorporated both the background data filtration step as well as the incorporation of collector covariates associated with the probability of collection. We found that month, method of collection and whether a collector had previously collected the focal species were important predictors of collection probability. Efforts to standardize meta-data associated with data collection will improve efforts for modeling the spatial distribution of a variety of species.