bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncertainties in supernova input rates drive qualitative differences in simulations of galaxy evolution
Authors: Keller Benjamin W , Kruijssen J M Diederik
Published: February 2022

Feedback from core collapse supernovae (SNe), the final stage of evolution of massive stars, is a key element in galaxy formation theory. The energy budget of SN feedback, as well as the duration over which SNe occur, are constrained by stellar lifetime models and the minimum mass star that ends its life as a SN. Simplifying approximations for this SN rate are ubiquitous in simulation studies. We show here how the choice of SN budget and timings (t0 for the delay between star formation and the first SN, τSN for the duration of SN injection, and the minimum SN progenitor mass) drive changes in the regulation of star formation and outflow launching. Extremely long delays for instantaneous injection of SN energy (t0 ≫ 20 Myr) reduces star formation and drive stronger outflows compared smaller delays. This effect is primarily driven by enhanced clustering of young stars. With continuous injection of energy, longer SN durations results in a larger fraction of SN energy deposited in low ambient gas densities, where cooling losses are lower. This is effect is particularly when driven by the choice of the minimum SN progenitor mass, which also sets the total SN energy budget. These underlying uncertainties mean that despite advances in the sub-grid modeling of SN feedback, serious difficulties in constraining the strength of SN feedback remain. We recommend future simulations use realistic SN injection durations, and bound their results using SN energy budgets and durations for minimum SN progenitors of 7 and 9 M⊙.
Impact of image persistence in theRoman Space TelescopeHigh-Latitude Survey
Authors: Lin Chien-Hao , Mandelbaum Rachel , Troxel M A , Hirata Christopher M , Jarvis Mike
Published: February 2022

The High-Latitude Survey of the Nancy Grace Roman Space Telescope is expected to measure the positions and shapes of hundreds of millions of galaxies in an area of 2220 deg2. This survey will provide high-quality weak lensing data with unprecedented systematic control. The Roman Space Telescope will survey the sky in near-infrared (NIR) bands using Teledyne H4RG HgCdTe photodiode arrays. These NIR arrays exhibit an effect called persistence: charges that are trapped in the photodiodes during earlier exposures are gradually released into later exposures, leading to contamination of the images and potentially to errors in measured galaxy properties such as fluxes and shapes. In this work, we use image simulations that incorporate the persistence effect to study its impact on galaxy shape measurements and weak lensing signals. No significant spatial correlations are found between the galaxy shape changes induced by persistence. On the scales of interest for weak lensing cosmology, the effect of persistence on the weak lensing correlation function is about two orders of magnitude lower than the Roman Space Telescope additive shear error budget, indicating that the persistence effect is expected to be a subdominant contributor to the systematic error budget for weak lensing with the Roman Space Telescope given its current design.
A 6.4-yr optical quasi-periodic oscillations in SDSS J075217.84+193542.2: a new candidate for central binary black hole system
Authors: Zhang XueGuang
Published: February 2022

In this manuscript, a 6.4-yr optical quasi-periodic oscillations (QPOs) is detected in the quasar SDSS J075217.84+193542.2 (=+SDSS J0752) at a redshift 0.117, of which 13.6-yr-long light curve from Catalina Sky Survey and All-Sky Automated Survey for Supernovae is directly described by a sinusoidal function with a periodicity 6.4 yr. The 6.4-yr QPOs can be further confirmed through the generalized Lomb–Scargle periodogram with confidence level higher than 99.99 per cent, and through the autocorrelation analysis results, and through the weighted wavelet z-transformation technique. The optical QPOs strongly indicate a central binary black hole (BBH) system in SDSS J0752. The determined two broad Gaussian components in the broad H α can lead to the BBH system with expected space separation about 0.02 pc between the expected two central BHs with determined virial BH masses about 8.8 × 107 and 1.04 × 109 M⊙. Meanwhile, we check the disc precessions applied to explain the optical QPOs. However, under the disc precession assumption, the determined optical emission regions from central BH have sizes about 40RG two times smaller than sizes of the expected Near UltraViolet (NUV) emission regions through the correlation between disc size and BH mass, indicating the disc precessions are not preferred. And due to the lower radio loudness around 0.28, jet precessions can be also totally ruled out. Furthermore, only 0.08 per cent probability can determined as the QPOs misdetected through light curves randomly created by the continuous autoregressive process, reconfirming the reported optical QPOs.
The evolution of the Si ivcontent in the Universe from the epoch of reionization to cosmic noon
Authors: D’Odorico V , Finlator K , Cristiani S , Cupani G , Perrotta S , Calura F , Cènturion M , Becker G , Berg T A M , Lopez S , Ellison S , Pomante E
Published: February 2022

We investigate the abundance and distribution of metals in the high-redshift intergalactic medium and circum-galactic medium through the analysis of a sample of almost 600 Si iv absorption lines detected in high- and intermediate-resolution spectra of 147 quasars. The evolution of the number density of Si iv lines, the column density distribution function, and the cosmic mass density are studied in the redshift interval 1.7 ≲ z ≲ 6.2 and for log N(Si iv) ≥ 12.5. All quantities show a rapid increase between z ∼ 6 and z ≲ 5 and then an almost constant behaviour to z ∼ 2 in very good agreement with what is already observed for C iv absorption lines. The present results are challenging for numerical simulations: When simulations reproduce our Si iv results, they tend to underpredict the properties of C iv, and when the properties of C iv are reproduced, the number of strong Si iv lines [log N(Si iv) > 14] is overpredicted.
Oscillating magnetized hybrid stars under the magnifying glass of multimessenger observations
Authors: Mariani Mauro , Tonetto Lucas , Rodríguez M Camila , Celi Marcos O , Ranea-Sandoval Ignacio F , Orsaria Milva G , Pérez Martínez Aurora
Published: February 2022

We model neutron stars as magnetized hybrid stars with an abrupt hadron–quark phase transition in their cores, taking into account current constraints from nuclear experiments and multimessenger observations. We include magnetic field effects considering the Landau level quantization of charged particles and the anomalous magnetic moment of neutral particles. We construct the magnetized hybrid equation of state, and we compute the particle population, the matter magnetization and the transverse and parallel pressure components. We integrate the stable stellar models, considering the dynamical stability for rapid or slow hadron–quark phase conversion. Finally, we calculate the frequencies and damping times of the fundamental and g non-radial oscillation modes. The latter, a key mode to learn about phase transitions in compact objects, is only obtained for stars with slow conversions. For low magnetic fields, we find that one of the objects of the GW170817 binary system might be a hybrid star belonging to the slow extended stability branch. For magnetars, we find that a stronger magnetic field always softens the hadronic equation of state. Besides, only for some parameter combinations a stronger magnetic field implies a higher hybrid star maximum mass. Contrary to previous results, the incorporation of anomalous magnetic moment does not affect the studied astrophysical quantities. We discuss possible imprints of the microphysics of the equation of state that could be tested observationally in the future, and that might help infer the nature of dense matter and hybrid stars.
The significant impact of shape deviations of atmospheric aerosols on light monitoring networks
Authors: Kómar Ladislav , Wallner Stefan , Kocifaj Miroslav
Published: February 2022

Aerosol particles are important modulators of night sky brightness (NSB) due to their manifold impacts on spectral and angular properties of scattered light. The majority of radiative transfer models currently in use are based on rigorous Mie theory for spherical homogeneous particles. This fundamental concept enables significant simplifications in theoretical formulae and numerical modelling. However, as known from many studies, spherical shapes are rare for both natural and anthropogenic aerosols. Therefore, the aim of this paper is to analyse the potential magnitude of the subsequent effect in skyglow modelling assuming that the aerosol particles are of different aspect ratios. The zero-order approximation to tackle the problem is to characterize the non-sphericity by the ratio of the largest to smallest size of an ellipsoidal particle. We use T-matrix formalism to perform light scattering calculations on spheroidal particles of arbitrary size, composition, and orientation in respect to the incident light. Results indicate that the particle-shape impact on NSB can be of significant size leading to both positive and negative amplitudes around the zenith. In the most extreme case, an increase of up to 70 per cent in zenithal luminance was displayed. As a consequence, especially light monitoring devices like the sky quality meter, usually measuring the NSB around the zenith, are particularly influenced by this effect. In summary, the paper underlines both the importance of treating non-spherical aerosols in theoretical modelling of skyglow and also the significance of including atmospheric parameters to analyses of light monitoring networks.
7,8-Dihydro-8-oxo-1,N6-ethenoadenine: an exclusively Hoogsteen-paired thymine mimic in DNA that induces A→T transversions in Escherichia coli
Authors: Aralov Andrey V , Gubina Nina , Cabrero Cristina , Tsvetkov Vladimir B , Turaev Anton V , Fedeles Bogdan I , Croy Robert G , Isaakova Ekaterina A , Melnik Denis , Dukova Svetlana , Ryazantsev Dmitriy Y , Khrulev Alexei A , Varizhuk Anna M , González Carlos , Zatsepin Timofei S , Essigmann John M
Published: February 2022

This work investigated the structural and biological properties of DNA containing 7,8-dihydro-8-oxo-1,N6-ethenoadenine (oxo-ϵA), a non-natural synthetic base that combines structural features of two naturally occurring DNA lesions (7,8-dihydro-8-oxoadenine and 1,N6-ethenoadenine). UV-, CD-, NMR spectroscopies and molecular modeling of DNA duplexes revealed that oxo-ϵA adopts the non-canonical syn conformation (χ = 65º) and fits very well among surrounding residues without inducing major distortions in local helical architecture. The adduct remarkably mimics the natural base thymine. When considered as an adenine-derived DNA lesion, oxo-ϵA was >99% mutagenic in living cells, causing predominantly A→T transversion mutations in Escherichia coli. The adduct in a single-stranded vector was not repaired by base excision repair enzymes (MutM and MutY glycosylases) or the AlkB dioxygenase and did not detectably affect the efficacy of DNA replication in vivo. When the biological and structural data are viewed together, it is likely that the nearly exclusive syn conformation and thymine mimicry of oxo-ϵA defines the selectivity of base pairing in vitro and in vivo, resulting in lesion pairing with A during replication. The base pairing properties of oxo-ϵA, its strong fluorescence and its invisibility to enzymatic repair systems in vivo are features that are sought in novel DNA-based probes and modulators of gene expression.
The nucleoporin Gle1 activates DEAD-box protein 5 (Dbp5) by promoting ATP binding and accelerating rate limiting phosphate release
Authors: Gray Shawn , Cao Wenxiang , Montpetit Ben , De La Cruz Enrique M
Published: February 2022

The DEAD-box protein Dbp5 is essential for RNA export, which involves regulation by the nucleoporins Gle1 and Nup159 at the cytoplasmic face of the nuclear pore complex (NPC). Mechanistic understanding of how these nucleoporins regulate RNA export requires analyses of the intrinsic and activated Dbp5 ATPase cycle. Here, kinetic and equilibrium analyses of the Saccharomyces cerevisiae Gle1-activated Dbp5 ATPase cycle are presented, indicating that Gle1 and ATP, but not ADP-Pi or ADP, binding to Dbp5 are thermodynamically coupled. As a result, Gle1 binds Dbp5-ATP > 100-fold more tightly than Dbp5 in other nucleotide states and Gle1 equilibrium binding of ATP to Dbp5 increases >150-fold via slowed ATP dissociation. Second, Gle1 accelerated Dbp5 ATPase activity by increasing the rate-limiting Pi release rate constant ∼20-fold, which remains rate limiting. These data show that Gle1 activates Dbp5 by modulating ATP binding and Pi release. These Gle1 activities are expected to facilitate ATPase cycling, ensuring a pool of ATP bound Dbp5 at NPCs to engage RNA during export. This work provides a mechanism of Gle1-activation of Dbp5 and a framework to understand the joint roles of Gle1, Nup159, and other nucleoporins in regulating Dbp5 to mediate RNA export and other Dbp5 functions in gene expression.
The pathway toward practical application of lithium-metal anodes for non-aqueous secondary batteries
Authors: Li Panlong , Fang Zhong , Dong Xiaoli , Wang Congxiao , Xia Yongyao
Published: February 2022

abstract

The revolution of automotive vehicles (from petrol vehicles to electric vehicles) has set high demands for the performance of batteries. Lithium-metal batteries (LMBs) show great potential owing to their high energy density but encounter poor cycle life and safety issues. It is of great significance to reveal LMB failure mechanisms and understand their relationship with battery performance. This review presents an overview of the state-of-the-art Li-metal anodes, with an emphasis on two typical failure modes: capacity degradation and dendritic growth of Li metal. The critical correlations between the composition, structure and failure are explained point by point. The chemical and electrochemical stabilities of the lithium anode are discussed. Particularly, for the first time, five types of lithium-metal anodes are classified to develop a comprehensive understanding of LMBs. Furthermore, strategies are suggested to improve the practical performance of LMBs, including material innovation, electrolyte modification and advanced characterization.
Redox mediators for high-performance lithium–oxygen batteries
Authors: Dou Yaying , Xie Zhaojun , Wei Yingjin , Peng Zhangquan , Zhou Zhen
Published: February 2022

Aprotic lithium–oxygen (Li–O2) batteries are receiving intense research interest by virtue of their ultra-high theoretical specific energy. However, current Li–O2 batteries are suffering from severe barriers, such as sluggish reaction kinetics and undesired parasitic reactions. Recently, molecular catalysts, i.e. redox mediators (RMs), have been explored to catalyse the oxygen electrochemistry in Li–O2 batteries and are regarded as an advanced solution. To fully unlock the capability of Li–O2 batteries, an in-depth understanding of the catalytic mechanisms of RMs is necessary. In this review, we summarize the working principles of RMs and their selection criteria, highlight the recent significant progress of RMs and discuss the critical scientific and technical challenges on the design of efficient RMs for next-generation Li–O2 batteries.
Searching for Professional Women in the Mid to Late Roman Textile Industry
Authors: Kelley Anna C
Published: February 2022

Since the 1960s, feminist historiography has been hard at work challenging established narratives of women’s roles in past societies, although with greater impact in some disciplines than others. Studies of production in the ancient world, in particular, continue to exclude women from discussions of professional labour. When women do appear in texts, modern scholarship has tended to treat them either as exceptional cases, or as part of an unskilled, casual workforce. Utilizing a variety of source materials, particularly Egyptian papyri, this article examines women’s labour in the mid to late Roman textile industry, which in recent historiography has typically been relegated to the category of ‘domestic’ production. Drawing upon a comparative model for women’s manufacturing roles in the Middle Ages to highlight important distinctions between women’s roles and their documentation in manufacturing between time periods, it becomes evident that Roman women were crucial actors at all stages of commercial textile production, although they possessed limited levels of control within the industry. Establishing women within the better-evidenced Roman textile sector, despite legal and social norms that historically obscured them, opens the possibility of finding professional women in other industries in the ancient world, and continues the process of re-evaluating the economic history of women throughout the ages.
Tackling barriers to COVID-19 vaccine uptake in London: a mixed-methods evaluation
Authors: Halvorsrud Kristoffer , Shand Jenny , Weil Leonora G , Hutchings Andrew , Zuriaga Ana , Satterthwaite Dane , Yip Jennifer L Y , Eshareturi Cyril , Billett Julie , Hepworth Ann , Dodhia Rakesh , Schwartz Ellen C , Penniston Rachel , Mordaunt Emma , Bulmer Sophie , Barratt Helen , Illingworth John , Inskip Joanna , Bury Fran , Jenkins Deborah , Mounier-Jack Sandra , Raine Rosalind
Published: February 2022

Background

In response to the COVID-19 pandemic, the first vaccine was administered in December 2020 in England. However, vaccination uptake has historically been lower in London than in other English regions.

Methods

Mixed-methods: This comprised an analysis of cumulative percentage uptake across London between 8 December 2020 and 6 June 2021 by vaccine priority cohorts and ethnicity. We also undertook thematic analyses of uptake barriers, interventions to tackle these and key learning from a qualitative survey of 27 London local authority representatives, vaccine plans from London’s five Integrated Care Systems and interviews with 38 London system representatives.

Results

Vaccine uptake was lower in Black ethnic (57–65% uptake) compared with the White British group (90% uptake). Trust was a critical issue, including mistrust in the vaccine itself and in authorities administering or promoting it. The balance between putative costs and benefits of vaccination created uptake barriers for zero-hour and shift workers. Intensive, targeted and ‘hyper-local’ initiatives, which sustained community relationships and were not constrained by administrative boundaries, helped tackle these barriers.

Conclusions

The success of the national vaccination programme depended on conceding local autonomy, investing in responsive and long-term partnerships to engender trust through in-depth understanding of communities’ beliefs.
Promoting osteointegration effect of Cu-alloyed titanium in ovariectomized rats
Authors: Zhang Xiyue , Liu Hui , Li Ling , Huang Cuishan , Meng Xiangbo , Liu Junzuo , Bai Xueling , Ren Ling , Wang Xinluan , Yang Ke , Qin Ling
Published: February 2022

Osteoporosis is a common skeletal disease making patients be prone to the osteoporotic fracture. However, the clinical implants made of titanium and its alloys with a poor osseointegration need a long time for healing and easily to loosening. Thus, a new class of Cu-alloyed titanium (TiCu) alloys with excellent mechanical properties and bio-functionalization has been developed. In this study, the osteoporosis modeled rats were used to study the osteointegration effect and underlying mechanism of TiCu. The results showed that after implantation for 4 weeks, TiCu alloy could promote the reconstruction of vascular network around the implant by up-regulating vascular endothelial growth factor expression. After 8 weeks, it could further promote the proliferation and differentiation of osteoblasts, mineralization and deposition of collagens, and then significantly increasing bone mineral density around the implant. In conclusion, TiCu alloy would enhance the fixation stability, accelerate the osteointegration, and thus reduce the risk of aseptic loosening during the long-term implantation in the osteoporosis environment. This study was the first to report the role and mechanism of a Cu-alloyed metal in promoting osteointegration in osteoporosis environment, which provides a new attractive support for the improvement of future clinical applications of Cu-alloyed antibacterial titanium alloys.
Personalized tourniquet pressure may be a better choice than uniform tourniquet pressure during total knee arthroplasty
Authors: Sun Changjiao , Yang Xin , Zhang Xiaofei , Ma Qi , Yu Peng , Cai Xu , Zhou Yonggang
Published: February 2022

Background:

Pneumatic tourniquets are widely used in total knee arthroplasty (TKA). Some surgeons prefer a uniform tourniquet inflation pressure (UTIP) for all patients; others use personalized tourniquet inflation pressures (PTIP) based on systolic blood pressure and limb occlusion pressure. However, no consensus exists regarding the optimal mode of inflation pressure during TKA. This review aimed to appraise if personalized tourniquet inflation pressures are better than uniform tourniquet inflation.

Methods:

The databases (Web of Science, Embase, PubMed, Cochrane Controlled Trials Register, Cochrane Library, Highwire, CBM, CNKI, VIP, Wanfang) were searched on March 2021 to systematically identify and screen the literature for randomized controlled trials involving PTIP and UTIP during total knee arthroplasty.

Results:

Thirteen randomized controlled trials, involving 1204 TKAs (1201 patients) were included in the systematic review. The meta-analysis identified a trend toward less visual analogue scale (VAS) score at rest with PTIP group at 1 day (P = .002), 2 to 3 days (P = .01), and less VAS score at activity 1 day (P < .0001), 2 to 3 days after the operation (P < .00001), and discharge (P < .0001). No significant difference was found between the groups in terms of VAS score at rest when discharge (P = 1.0). We also found no significant difference in terms of intraoperative blood loss (P = .48), total blood loss (P = .15), lower limb vein thrombosis (P = .42), and thigh bullae (P = .17). However, in the PTIP group, we found a significant higher hospital for special surgery (HSS) score (P = .007), broader knee Range of motion (P = .02), less rate of thigh ecchymosis (P = .00001), and shorter thigh circumference at 1 day (P = .006), 2 to 3 days (P = .0005), and discharge (P = .02).

Conclusion:

PTIP provides a similar bloodless surgical field compared with the conventional UTIP. Furthermore, PTIP provides less pain intensity, thigh circumference, rate of thigh ecchymosis, higher hospital for special surgery, and better initial recovery of knee flexion in total knee arthroplasty. Therefore, we recommend using a PTIP method during TKA. More adequately powered and better-designed randomized controlled trials studies with long-term follow-up are required to produce evidence-based guidelines regarding the PTIP method.
Expression of Unfolded Protein Response Genes in Post-transplantation Liver Biopsies
Authors: Liu Xiaoying , Taylor Sarah A. , Celaj Stela , Levitsky Josh , Green Richard M.
Published: February 2022

Cholestatic liver diseases are a major source of morbidity and mortality that can progress to end-stage liver disease. There are few effective medical therapies for primary biliary cholangitis, primary sclerosing cholangitis and other cholestatic liver diseases, in part, due to our incomplete understanding of the pathogenesis of cholestatic liver injury. The hepatic unfolded protein response (UPR) is an adaptive cellular response to endoplasmic reticulum stress that is important in the pathogenesis of many liver diseases and recent animal studies have demonstrated the importance of the UPR in the pathogenesis of cholestatic liver injury. However, the role of the UPR in human cholestatic liver diseases is largely unknown. In this study, we utilized liver biopsies from patients after liver transplantation as a disease model to determine the transcriptional profile and hepatic UPR gene expression that is associated with liver injury and cholestasis. RNA-seq analysis revealed that patients with hyperbilirubinemia had enhanced expression of hepatic UPR pathways. Alternatively, liver biopsy samples from patients with acute rejection had enhanced gene expression ofLAG3andCDK1. Pearson correlation analysis of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin levels demonstrated significant correlations with the hepatic expression of several UPR genes, as well as genes involved in hepatic bile acid metabolism and inflammation. In contrast, serum alkaline phosphatase levels were correlated with the level of hepatic bile acid metabolism gene expression but not liver UPR gene expression.

Conclusion

Overall, these data indicate that hepatic UPR pathways are increased in cholestatic human liver biopsy samples and supports an important role of the UPR in the mechanism of human cholestatic liver injury.
Antisense modulation of IL7R splicing to control sIL7R expression in human CD4+T cells
Authors: Galarza-Muñoz Gaddiel , Kennedy-Boone Debbie , Schott Geraldine , Bradrick Shelton S. , Garcia-Blanco Mariano A.
Published: February 2022

The interleukin 7 receptor (IL7R) is strongly associated with increased risk to develop multiple sclerosis (MS), an autoimmune disease of the central nervous system, and this association is likely driven by upregulation of the soluble isoform of IL7R (sIL7R). Expression of sIL7R is determined by exclusion of the alternative exon 6 from IL7R transcripts, and our previous work revealed that the MS risk allele of the SNP rs6897932 within this exon enhances the expression of sIL7R by promoting exclusion of exon 6. sIL7R potentiates the activity of IL7, leading to enhanced expansion of T cells and increased disability in the Experimental Autoimmune Encephalomyelitis (EAE) murine model of MS. This role in modulating T cell-driven immunity positions sIL7R as an attractive therapeutic target whose expression could be reduced for treatment of MS or increased for treatment of cancers. In this study we identified novel antisense oligonucleotides (ASOs) that effectively control the inclusion (anti-sIL7R ASOs) or exclusion (pro-sIL7R ASOs) of this exon in a dose-dependent fashion. These ASOs provided excellent control of exon 6 splicing and sIL7R secretion in human primary CD4+T cells. Supporting their potential for therapeutic targeting, we showed that lead anti-sIL7R ASOs correct the enhanced exon 6 exclusion imposed by the MS risk allele of rs6897932, whereas lead pro-sIL7R ASOs phenocopy it. The data presented here form the foundation for future pre-clinical studies that will test the therapeutic potential of these ASOs in MS and immuno-oncology.
Uncovering circuit mechanisms of current sinks and sources with biophysical simulations of primary visual cortex
Authors: Rimehaug Atle E. , Stasik Alexander J. , Hagen Espen , Billeh Yazan N. , Siegle Joshua H. , Dai Kael , Olsen Shawn R. , Koch Christof , Einevoll Gaute T. , Arkhipov Anton
Published: February 2022

Local field potential (LFP) recordings reflect the dynamics of the current source density (CSD) in brain tissue. The synaptic, cellular and circuit contributions to current sinks and sources are ill-understood. We investigated these in mouse primary visual cortex using public Neuropixels recordings and a detailed circuit model based on simulating the Hodgkin-Huxley dynamics of numerous cortical neurons belonging to 17 cell types. The model simultaneously captured spiking and CSD responses and demonstrated a two-way dissociation: Firing rates are altered with minor effects on the CSD pattern by adjusting synaptic weights, and CSD is altered with minor effects on firing rates by adjusting synaptic placement on the dendrites. We describe how thalamocortical inputs and recurrent connections sculpt specific sinks and sources early in the visual response, whereas cortical feedback crucially alters them in later stages. Our findings show that CSD analysis provides powerful constraints for modeling beyond those from considering spikes.
Dynamic Generalised Additive Models (DGAM) for forecasting discrete ecological time series
Authors: Clark Nicholas J , Wells Konstans
Published: February 2022

Generalised Additive Models (GAMs) are increasingly popular for describing smooth nonlinear relationships between predictors and response variables. GAMs are particularly relevant in ecology for representing hierarchical functions for discrete responses that encompass complex features including zero-inflation, bounding and uneven sampling. However, GAMs are less useful for producing forecasts as their smooth functions provide unstable predictions outside the range of training data.

We introduce Dynamic Generalised Additive Models (DGAMs), where the GAM linear predictor is jointly estimated with unobserved dynamic components to model time series that evolve as a function of nonlinear predictor associations and latent temporal processes. These models are particularly useful for multivariate series, as they can estimate hierarchical smooths while learning complex temporal associations via dimension-reduced latent factor processes. We implement our models in themvgamR package, which uses themgcvandrjagspackages to construct smoothing splines and estimate unobserved parameters in a probabilistic framework.

Using simulations, we illustrate how our models outperform competing formulations in realistic ecological forecasting tasks while identifying important smooth predictor functions. We use a real-world case study to highlight some ofmvgam’skey features, which include functions for: calculating correlations among series’ latent trends, performing model selection using rolling window forecasts, online data augmentation via a recursive particle filter, and visualising probabilistic uncertainties for smooths and predictions.

Dynamic GAMs (DGAM) offer a solution to the challenge of forecasting discrete time series while estimating ecologically relevant nonlinear predictor associations. Our Bayesian latent factor approach will be particularly useful for exploring competing dynamic ecological models that encompass hierarchical smoothing structures while providing forecasts with robust uncertainties, tasks that are becoming increasingly important in applied ecology.
Genomic surveillance of SARS-CoV-2 reveals emergence of Omicron BA.2 in Islamabad, Pakistan
Authors: Umair Massab , Ikram Aamer , Rehman Zaira , Haider Syed Adnan , Ammar Muhammad , Badar Nazish , Ali Qasim , Rana Muhammad Suleman , Salman Muhammad
Published: February 2022

The Omicron variant of SARS-CoV-2 has rapidly replace previous variants of SARS CoV2 around the globe and is now a major variant of concern. The genomic surveillance of Omicron variant also reveals spread of its subvariant BA.2 which has differing transmissibility in comparison to its other subvariant BA.1. BA.1 and BA.2 harbors different mutational profile. One of the important change in both the subvariants is the presence of 69-70 deletion in BA.1 and absence of this deletion in BA.2. This deletion can be used as tool for the detection of omicron sub variants using real time PCR. In the current study we have used the TaqPath COVID-19 PCR kit for the detection of 69-70 deletion followed by genotyping using SNPsig® SARS-CoV-2 (EscapePLEX) kit (PrimerDesign, UK) that target K417N, E484K, and P681R mutations. The samples with the amplification of spike gene and K417N were termed as probable BA.2 cases. A subset of samples (n=13) were further subjected to whole genome sequencing. The results showed all the 13 samples were of BA.2. Hence, this assay can be used as a cost effective method for the detection of omicron BA.2 variant using real time PCR in resource limiting settings. Moreover, the detection of BA.2 with highly transmissible mutations in Islamabad, Pakistan may potentially increase the number of positive cases. In that scenario, there has to be stringent genomic surveillance to understand the circulating lineages in the country.
Modeling predicts mechanisms altered by mutations of the SARS-CoV-2 delta and omicron variants
Authors: Pearson Jason , Wessler Timothy , Chen Alex , Boucher Richard C. , Freeman Ronit , Lai Samuel K. , Pickles Raymond , Forest M. Gregory
Published: February 2022

We apply our mechanistic, within-host,pre-immunity, respiratory tract infection model for unvaccinated, previously uninfected, and immune-compromised individuals. Starting from published cell infection and viral replication data for the SARS-CoV-2 alpha variant, we explore variability in outcomes of viral load and cell infection due to three plausible mechanisms altered by SARS-CoV-2 mutations of delta and omicron. We seek a mechanistic explanation of clinical test results: delta nasal infections express ∼3 orders-of-magnitude higher viral load than alpha, while omicron infections express an additional 1 to 2 orders-of-magnitude rise over delta. Model simulations revealshortening of the eclipse phase(the time between cellular uptake of the virus and onset of infectious viral replication and shedding)alone can generate 3-5 orders-of-magnitude higher viral load within 2 days post initial infection. Higher viral replication rates by an infected cell can generate at most one order-of-magnitude rise in viral load, whereas higher cell infectability has minimal impact and lowers the viral load.
Fuzzy Supertertiary Interactions within PSD-95 Enable Ligand Binding
Authors: Hamilton George L. , Saikia Nabanita , Basak Sujit , Welcome Franceine S. , Wu Fang , Kubiak Jakub , Zhang Changcheng , Hao Yan , Seidel Claus A.M. , Ding Feng , Sanabria Hugo , Bowen Mark E.
Published: February 2022

The scaffold protein PSD-95 links postsynaptic receptors to sites of presynaptic neurotransmitter release. Flexible linkers between folded domains in PSD-95 enable a dynamic supertertiary structure. Interdomain interactions within the PSG supramodule, formed by PDZ3, SH3 and GuK domains, regulate PSD-95 activity. Here we combined Discrete Molecular Dynamics and single molecule FRET to characterize the PSG supramodule, with time resolution spanning picoseconds to seconds. We used a FRET network to measure distances in full-length PSD-95 and model the conformational ensemble. We found that PDZ3 samples two conformational basins, which we confirmed with disulfide mapping. To understand effects on activity, we measured binding of the synaptic adhesion protein neuroligin. We found that PSD-95 bound neuroligin well at physiological pH while truncated PDZ3 bound poorly. Our hybrid structural models reveal how the supertertiary context of PDZ3 enables recognition of this critical synaptic ligand.
Omicron BA.1 and BA.2 are antigenically distinct SARS-CoV-2 variants
Authors: Mykytyn Anna Z. , Rissmann Melanie , Kok Adinda , Rosu Miruna E. , Schipper Debby , Breugem Tim I. , van den Doel Petra B. , Chandler Felicity , Bestebroer Theo , de Wit Maurice , van Royen Martin E. , Molenkamp Richard , Oude Munnink Bas B. , de Vries Rory D. , GeurtsvanKessel Corine , Smith Derek J. , Koopmans Marion P. G. , Rockx Barry , Lamers Mart M. , Fouchier Ron , Haagmans Bart L.
Published: February 2022

The emergence and rapid spread of SARS-CoV-2 variants may impact vaccine efficacy significantly1. The Omicron variant termed BA.2, which differs genetically substantially from BA.1, is currently replacing BA.1 in several countries, but its antigenic characteristics have not yet been assessed2,3. Here, we used antigenic cartography to quantify and visualize antigenic differences between SARS-CoV-2 variants using hamster sera obtained after primary infection. Whereas early variants are antigenically similar, clustering relatively close to each other in antigenic space, Omicron BA.1 and BA.2 have evolved as two distinct antigenic outliers. Our data show that BA.1 and BA.2 both escape (vaccine-induced) antibody responses as a result of different antigenic characteristics. Close monitoring of the antigenic changes of SARS-CoV-2 using antigenic cartography can be helpful in the selection of future vaccine strains.
Epstein-Barr virus promotes T cell dysregulation in a humanized mouse model of multiple sclerosis
Authors: Allanach Jessica R. , Fettig Naomi M. , Hardman Blair K. , Fan Vina , Rosen Ariel R. , Goldberg Erin J. , Morse Zachary J. , Shanina Iryna , Vorobeychik Galina , Osborne Lisa C. , Horwitz Marc S.
Published: February 2022

Infection with the human-tropic Epstein-Barr virus (EBV) is a strong risk factor for multiple sclerosis (MS), though the underlying mechanisms remain unclear. To investigate the immunomodulatory effects of latent EBV infection, we induced experimental autoimmune encephalomyelitis (EAE) in immunocompromised mice humanized with peripheral blood mononuclear cells (PBMCs) from individuals with or without a history of EBV infection and/or a diagnosis of relapsing MS. HuPBMC EAE mice generated from EBV seronegative healthy donors were less susceptible to developing severe clinical disease than EBV seropositive healthy donor and RRMS cohorts. Donor EBV seropositivity and RRMS led to a significant incremental increase in the number of brain and spinal cord infiltrating effector T cells, in the absence of viral reactivation, due to enhanced proliferation of donor T cells and reduced regulatory T cell expansion. The data indicate that a history of EBV infection, further compounded by a diagnosis of RRMS, promotes T cell-mediated disease in a novel humanized mouse model of MS.

In a novel humanized mouse model of multiple sclerosis (MS), donor history of Epstein-Barr virus (EBV) infection exacerbates disease severity by skewing the balance of effector and regulatory T cells in the brain and spinal cord. These results reveal an immunomodulatory mechanism by which latent EBV infection could predispose to the development of autoimmune disease.
Targetome analysis of malaria sporozoite transcription factor AP2-Sp reveals its role as a master regulator
Authors: Yudaa Masao , Kaneko Izumi , Murata Yuho , Iwanaga Shiroh , Nishi Tsubasa
Published: February 2022

Malaria transmission to humans begins with sporozoite infection of the liver. The elucidation of gene regulation during the sporozoite stage will promote the investigation of mechanisms of liver infection by this parasite and contribute to the development of strategies for preventing malaria transmission. AP2-Sp is a transcription factor (TF) essential for the formation of sporozoites or sporogony, which takes place in oocysts in the midgut of infected mosquitoes. To understand the role of this TF in the transcriptional regulatory system of this stage, we performed ChIP-seq analyses using whole mosquito midguts containing late oocysts as starting material and explored its genome-wide target genes. We identified 697 target genes, comprising those involved in distinct processes parasites experience during this stage, from sporogony to development into the liver-stage, and representing the majority of genes highly expressed in the sporozoite stage. These results suggest that AP2-Sp determines basal patterns of gene expression by targeting a broad range of genes directly. The ChIP-seq analyses also showed that AP2-Sp maintains its own expression by a transcriptional auto-activation mechanism (positive feedback loop) and induces all TFs reported to be transcribed at this stage, including AP2-Sp2, AP2-Sp3, and SLARP. The results showed that AP2-Sp exists at the top of the transcriptional cascade of this stage and triggers the formation of this stage as a master regulator.
The impact of COVID passport mandates on the number of cases of and hospitalizations with COVID-19 in the UK: a difference-in-differences analysis
Authors: López-Güell Kim , Prats-Uribe Albert , Català Martí , Prats Clara , Hein Jotun , Prieto-Alhambra Daniel
Published: February 2022

Background

Mandatory COVID-19 certification was introduced at different times in the four countries of the UK. We aimed to study the effect of this intervention on the incidence of cases and hospital admissions.

Methods

The main outcome was the weekly averaged incidence of COVID-19 confirmed cases and hospital admissions. We performed Negative Binomial Segmented Regression (NBSR) and Autoregressive Integrated Moving Average (ARIMA) analyses for the four countries (England, Northern Ireland, Scotland and Wales), and fitted Difference-in-Differences (DiD) models to compare the latter three to England, where COVID-19 certification was imposed the latest.

Findings

NBSR methods suggested COVID-19 certification led to a decrease in the incidence of cases in Northern Ireland, but not in hospitalizations. In Wales, they also caused a decrease in the incidence of cases but not in hospital admissions. In Scotland, we observed a decrease in both cases and admissions. ARIMA models confirmed these results. The DiD model showed that the intervention decreased the incidence of COVID compared to England in all countries except Wales, in October. Then, the incidence rate of cases already had a decreasing tendency, as well as in England, hence a particular impact of Covid Passport was less obvious. In Wales, the model coefficients were 2.2 (95% CI -6.24,10.70) for cases and -0.144 (95% CI -0.248, -0.039) for admissions in October and -7.75 (95% CI -13.1, -2.46) for cases and -0.169 (95% CI-0.308, -0.031) for admissions in November. In Northern Ireland, -10.1 (95% CI -18.4, -1.79) for cases and -0.269 (95% CI -0.385, -0.153) for admissions. In Scotland they were 7.91 (95% CI 4.46,11.4) for cases and -0.097 (95% CI - 0.219,0.024) for admissions.

Interpretation

The introduction of mandatory certificates decreased cases in all countries except in England. Differences on concomitant measures, on vaccination uptake or Omicron variant prevalence could explain this discrepancy.
Mapping publication outputs, collaboration networks, research hotspots, and most cited articles in systematic reviews and meta-analyses of medicine and health sciences in Ethiopia: analyses of 20 years of scientific data
Authors: Habtewold Tesfa Dejenie , Sharew Nigussie Tadesse , Endalamaw Aklilu , Mulugeta Henok , Dessie Getenet , Asefa Nigus G. , Kassa Getachew Mulu , Bayih Wubet Alebachew , Birhanu Mulugeta Molla , Tegegne Balewgize Sileshi , Teferra Andreas A. , Tura Abera Kenay , Alemu Sisay Mulugeta
Published: February 2022

Introduction

Although the publication of systematic reviews (SR) and meta-analyses (MA) has substantially grown in Ethiopia, no robust study systematically characterized these SR and MA was conducted. Thus, we aimed to map publication outputs, collaboration networks, research hotspots, and most cited SR and MA of medicine and health sciences in Ethiopia.

Methods

We conducted a bibliometric study of SR and MA published up to December 31, 2021, and systematically searched via PubMed, PsycInfo, EMBASE, and Web of Science databases. We included all SR and MA in medicine and health sciences fields in Ethiopia irrespective of the authors’ affiliation and place of publication. Full records and cited references’ meta-data were extracted from the Web of Science Core Collection database. VOSviewer software was used to perform bibliometric analyses. The relevance of an item (e.g. author, country, or keywords) was measured by its weight based on frequencies using the full or binary counting method) and strength of the link between items was measured using total link strength.

Results

In total, 422 SR and MA were published between 2001 and 2021 by 14 research groups (i.e. overall, 1,066 authors participated) who affiliated with institutions from 33 countries. The largest number of SR and MA were published by authors affiliated with Debre Markos University, University of Gondar and Bahir Dar University. In addition, strong collaboration was observed among authors affiliated with institutions in Ethiopia, the Netherlands, Australia, and Canada. The identified research hotspots were maternal and child health, depression and substance use, cardiometabolic diseases, infectious diseases, HIV/AIDS, hepatitis and nutrition. The most cited SR was about domestic violence against women published in 2015. The SR and MA were published in 160 journals, with a majority published in PLOS (11%) and BMC (25%) journals.

Conclusions

In this study, we provide a comprehensive summary of collaboration networks, research hotspots, and most cited SR and MA to gain a deeper understanding of the landscape of SR and MA research in Ethiopia. We believe that our study informs researchers, higher institutions, and policymakers about research hotspots and gaps in medicine and health sciences research in Ethiopia. The national and international collaboration is promising, and a concerted effort among researchers, policymakers and funding agencies could increase research outputs and broaden research areas.
The Eucalyptus grandis chloroplast proteome: leaf development and seasonal variations
Authors: Baldassi Amanda Cristina , Balbuena Tiago Santana
Published: February 2022

Chloroplast metabolism is very sensitive to environmental fluctuations and is intimately related to plant leaf development. Characterization of the chloroplast proteome dynamics may contribute to enlarge the understanding on plant adaptation to different climate scenarios and leaf development processes. Herein, we carried out a discovery-driven proteome analysis of the Eucalyptus grandis chloroplast proteome during leaf maturation and throughout different seasons of the year. The chloroplast proteome from young leaves differed the most from all assessed samples. Most up-regulated proteins identified in mature and young leaves were those related to catabolic-redox signaling and biogenesis processes, respectively. Seasonal dynamics revealed unique proteome features in the autumn and spring periods. The most abundant chloroplast protein in humid (wet) seasons (spring and summer) was a small subunit of RuBisCO, while in the dry periods (fall and winter) the proteins that showed the most pronounced accumulation were associated with photo-oxidative damage, Calvin cycle, shikimate pathway, and detoxification. Our investigation of the chloroplast proteome dynamics during leaf development revealed significant alterations in relation to the maturation event. Our findings also suggest that transient seasons induced the most pronounced chloroplast proteome changes over the year. This study contributes to a more comprehensive understanding on the subcellular mechanisms that lead to plant leaf adaptation and ultimately to Eucalyptus grandis productivity. Mass spectrometric data are available via ProteomeXchange under identifier PXD029004.