bluuebunny/crossref_metadata_2025 huggingface dataset:
The deep population history in Africa
Authors: Hollfelder Nina , Breton Gwenna , Sjödin Per , Jakobsson Mattias
Published: January 2021

Africa is the continent with the greatest genetic diversity among humans and the level of diversity is further enhanced by incorporating non-majority groups, which are often understudied. Many of today’s minority populations historically practiced foraging lifestyles, which were the only subsistence strategies prior to the rise of agriculture and pastoralism, but only a few groups practicing these strategies remain today. Genomic investigations of Holocene human remains excavated across the African continent show that the genetic landscape was vastly different compared to today’s genetic landscape and that many groups that today are population isolate inhabited larger regions in the past. It is becoming clear that there are periods of isolation among groups and geographic areas, but also genetic contact over large distances throughout human history in Africa. Genomic information from minority populations and from prehistoric remains provide an invaluable source of information on the human past, in particular deep human population history, as Holocene large-scale population movements obscure past patterns of population structure. Here we revisit questions on the nature and time of the radiation of early humans in Africa, the extent of gene-flow among human populations as well as introgression from archaic and extinct lineages on the continent.
Novel variants and cellular studies on patients’ primary fibroblasts support a role forNEK1missense variants in ALS pathogenesis
Authors: Lattante Serena , Doronzio Paolo Niccolò , Conte Amelia , Marangi Giuseppe , Martello Francesco , Bisogni Giulia , Meleo Emiliana , Colavito Davide , Del Giudice Elda , Patanella Agata Katia , Bernardo Daniela , Romano Angela , Zollino Marcella , Sabatelli Mario
Published: January 2021

In the last few years, NEK1 has been identified as a new gene related to amyotrophic lateral sclerosis (ALS). Loss-of-function variants have been mostly described, although several missense variants exist, which pathogenic relevance remains to be established. We attempted to determine the contribution of NEK1 gene in an Italian cohort of 531 sporadic and familial amyotrophic lateral sclerosis (ALS) patients applying massive parallel sequencing technologies. We filtered results of NEK1 gene and identified 20 NEK1 rare variants (MAF < 0.01) in 22 patients. In particular, we found two novel frameshift variants (p.Glu929Asnfs*12 and p.Val1030Ilefs*23), 18 missense variants, including the p.Arg261His in three patients, and a novel variant in the start codon, the p.Met1?, which most likely impairs translation initiation. To clarify the role of NEK1 missense variants we investigated NEK1 expression in primary fibroblast cultures. We obtained skin biopsies from four patients with NEK1 variants and we assessed NEK1 expression by western blot and immunofluorescence. We detected a decrease in NEK1 expression in fibroblasts from patients with NEK1 variants, suggesting that missense variants in NEK1 gene may have a pathogenic role. Moreover, we observed additional variants in ALS related genes in seven patients with NEK1 variants (32%), further supporting an oligogenic ALS model.
Genetic evidence and historical theories of the Asian and African origins of the present Malagasy population
Authors: Heiske Margit , Alva Omar , Pereda-Loth Veronica , Van Schalkwyk Matthew , Radimilahy Chantal , Letellier Thierry , Rakotarisoa Jean-Aimé , Pierron Denis
Published: January 2021

The origin of the Malagasy population has been a subject of speculation since the 16th century. Contributions of African, Asian, Indian, Melanesian, Arabic and Persian populations have been suggested based on physical and cultural anthropology, oral tradition, linguistics and later also by archaeology. In the mid-20th century, increased knowledge of heredity rules and technical progress enabled the identification of African and Asian populations as main contributors. Recent access to the genomic landscape of Madagascar demonstrated pronounced regional variability in the relative contributions of these two ancestries, yet with significant presence of both African and Asian components throughout Madagascar. This article reviews the extent to which genetic results have settled historical questions concerning the origin of the Malagasy population. After an overview of the early literature, the genetic results of the 20th and 21th centuries are discussed and then complemented by the latest results in genome-wide analyses. While there is still much uncertainty regarding when, how and the circumstances under which the ancestors of the modern Malagasy population arrived on the island, we propose a scenario based on historical texts and genomic results.
Impacts of jellyfish on marine cage aquaculture: an overview of existing knowledge and the challenges to finfish health
Authors: Clinton Morag , Ferrier David E K , Martin Samuel A M , Brierley Andrew S
Published: January 2021

Gelatinous plankton present a challenge to marine fish aquaculture that remains to be addressed. Shifting plankton distributions, suggested by some to be a result of factors such as climate change and overfishing, appear to be exacerbated by anthropogenic factors linked directly to aquaculture. Fish health can be negatively influenced by exposure to the cnidarian hydrozoan and scyphozoan life stages commonly referred to as “jellyfish”. Impact is particularly pronounced in gill tissue, where three key outcomes of exposure are described; direct traumatic damage, impaired function, and initiation of secondary disease. Cnidarian jellyfish demonstrated to negatively impact fish include Cyanea capillata, Aurelia aurita, and Pelagia noctiluca. Further coelenterates have also been associated with harm to fish, including sessile polyps of species such as Ectopleura larynx. An accurate picture of inshore planktic exposure densities within the coastal environments of aquaculture would aid in understanding cnidarian species of concern, and their impact upon fish health, particularly in gill disease. This information is however presently lacking. This review summarises the available literature regarding the impact of gelatinous plankton on finfish aquaculture, with a focus on cnidarian impact on fish health. Present strategies in monitoring and mitigation are presented, alongside identified critical knowledge gaps.
Modelling of a calcium-looping fluidized bed reactor system for carbon dioxide removal from flue gas
Authors: Maparanyanga Tsitsi , Lokhat David
Published: January 2021

Calcium-looping process was simulated by solution of one-dimensional mass and energy balance equations for both interconnected fluidized bed reactors. Kinetics for the carbonator and calciner were derived from literature sources and were revised to include the effects of sulphation. The degree of apparent carbonation was compared to the actual level of carbon dioxide removal through a series of sensitivity analyses. It has been found that carbonation decreases with an increase in temperature. Sulphation increases with an increase in temperature. The activity of calcium oxide decreases with an increase in carbonation–calcination cycles. Neglecting the effect of sulphation during the design of the calcium-looping system leads to overestimation of active calcium particles that will react with carbon dioxide.
Efficacy estimation of a combination of triple antimicrobial agents against clinical isolates of Mycobacterium abscessus subsp. abscessus in vitro
Authors: Asami Takahiro , Aono Akio , Chikamatsu Kinuyo , Igarashi Yuriko , Morishige Yuta , Murase Yoshiro , Yamada Hiroyuki , Takaki Akiko , Mitarai Satoshi
Published: January 2021

Background

Mycobacterium abscessus subsp. abscessus (M. abscessus) is a rapidly growing mycobacterium that is resistant to most antibiotics. The number of patients with pulmonary disease caused by M. abscessus is increasing in several regions, and therapy involves long-term antibiotic combination treatments, although no standard treatment regimen has been established.

Objectives

To examine candidate regimens for maintenance of antimicrobial treatment against M. abscessus by measuring MIC using the three-drug chequerboard method.

Methods

We evaluated the drug susceptibility of 70 clinical isolates of M. abscessus using the three-drug chequerboard method. We tested the antimycobacterial agents bedaquiline, clofazimine, amikacin, and sitafloxacin (which showed a relatively low MIC range when used as single agents) alone and in combinations.

Results

The three-drug combinations of bedaquiline/clofazimine/amikacin, and bedaquiline/clofazimine/sitafloxacin were studied. Among isolates for which the fractional inhibitory concentration index (FICI) could be calculated, 29/70 isolates (41%) and 11/70 isolates (16%) showed a synergistic response (FICI ≤0.75) with combined use of bedaquiline/clofazimine/amikacin, or with bedaquiline/clofazimine/sitafloxacin, respectively.

Conclusions

The combination of bedaquiline with clofazimine plus either amikacin or sitafloxacin may be useful as maintenance regimens when treating pulmonary disease caused by M. abscessus.
The Lethal Cutting: An Unexpected Cause of Death—A Methomyl Acute Intoxication
Authors: Di Candia Domenico , Boracchi Michele , Muccino Enrico , Gentile Guendalina , Zoja Riccardo
Published: January 2021

Cocaine is among the illicit substances most frequently implicated in deaths related to the use of drugs of abuse both worldwide and in Italy. Cutting agents involved in the adulterations of this substance are many, and the process of lacing can take place at various stages of the production of the drug. In this report we are discussing the case of a 27-year-old woman found dead next to her car in a wooded area in the suburban area of Milan. On the crime scene, several specimens of white powder were collected and subsequently analyzed via Q-Exactive Orbitrap with an high performance liquid chromatography system and liquid chromatography--tandem mass spectrometry analysis along with biological matrices sampled during autopsy examination. The toxicological analysis revealed that the death could be ascribed to a lethal dose of methomyl, a carbamide pesticide used as cutting agent for cocaine. According to literature, this is the first time that this substance is used as an adulterant.
Ovary-Specific Transcriptome and Essential Role ofNanosin Ovary Development in the Oriental Fruit Fly (Diptera: Tephritidae)
Authors: Hou Qiu-Li , Chen Er-Hu , Xie Yi-Fei , Dou Wei , Wang Jin-Jun
Published: January 2021

We used transcriptome analysis to research ovary development in Bactrocera dorsalis (Hendel). The ovary transcriptome of B. dorsalis yielded 66,463,710 clean reads that were assembled into 23,822 unigenes. After aligning to the Nr database in NCBI, 15,473 (64.95%) of the unigenes were matched to identified proteins. As determined by BLAST search, 11,043 (46.36%), 6,102 (25.61%), and 12,603 (52.90%) unigenes were each allocated to clusters via gene ontology, orthologous groups, and SwissProt, respectively. The Kyoto encyclopedia database of genes and genomes (KEGG) was further used to annotate these sequences, and 11,068 unigenes were mapped to 255 known pathways. Afterward, the genes that were possibly involved in oogenesis and ovary development were obtained from the transcriptome data and analyzed. Interestingly, seven ovary-specific genes were identified, including a Nanos gene that is involved in maintaining the primordial germ cells in many insects. Therefore, we further focused on the function of the BdNanos gene, and the gene was injected into B. dorsalis. As expected, the knocking down of Nanos gene expression led to significant inhibition of ovary development, suggesting an important role of this gene in the reproductive process of B. dorsalis. In summary, the present study provides an important reference for identifying the molecular mechanisms of oogenesis and ovary development in B. dorsalis. The BdNanos gene is crucial for ovary development in B. dorsalis and is therefore a potential new pest control target.
The Museum as a Model for a Human Rights-Based Future: The International Slavery Museum, Liverpool, UK
Authors: Ostow Robin
Published: January 2021

This article explores the social and political history of the International Slavery Museum in Liverpool, UK. Using ethnographic and historical research, it discusses the museum’s origins in the aftermath of the Toxteth disturbances of 1981, its permanent exhibit, its activist projects and its relations with Liverpool’s Black community. It argues that the International Slavery Museum responds to Samuel Moyn’s criticism that human rights theory and practice address past and present abuses, but fail to provide a vision for the future, by supporting human rights culture and organizations and by developing a model for a human rights-based, future oriented organization.
Risk Reduction and Efficiency Increase in Large Portfolios: Gross-Exposure Constraints and Shrinkage of the Covariance Matrix
Authors: Zhao Zhao , Ledoit Olivier , Jiang Hui
Published: January 2021

We investigate the effects of constraining gross-exposure and shrinking covariance matrix in constructing large portfolios, both theoretically and empirically. Considering a wide variety of setups that involve conditioning or not conditioning the covariance matrix estimator on the recent past (multivariate GARCH), smaller versus larger universe of stocks, alternative portfolio formation objectives (global minimum variance versus exposure to profitable factors), and various transaction cost assumptions, we find that a judiciously chosen shrinkage method always outperforms an arbitrarily determined constraint on gross-exposure. We extend the mathematical connection between constraints on the gross-exposure and shrinkage of the covariance matrix from static to dynamic, and provide a new explanation for our finding from the perspective of degrees of freedom. In addition, both simulation and empirical analysis show that the dynamic conditional correlation-nonlinear shrinkage (DCC-NL) estimator results in risk reduction and efficiency increase in large portfolios as long as a small amount of short position is allowed, whereas imposing a constraint on gross-exposure often hurts a DCC-NL portfolio.
Estimating the Speed of Adjustment of Leverage in the Presence of Interactive Effects
Authors: Westerlund Joakim , Karabiyik Hande , Narayan Paresh Kumar , Narayan Seema
Published: January 2021

Dynamic panel data regression models with fixed effects to account for unobserved heterogeneity are standard econometric tools. It is not until recently, however, that the problems involved when fitting such regressions to leverage data have been investigated. The main problem is that models of leverage are extremely noisy, much more so than what can be accommodated using fixed effects. The present article can be seen as a reaction to this. The purpose is to consider a more general interactive effects model in which there are multiple time effects, each with their own firm-specific sensitivities. Our empirical results suggest that proper accounting for the interactive effects and the bias that they cause leads to a marked increase in the estimated speed of adjustment to target leverage.
Deficit Accumulation Frailty Trajectories of Older Breast Cancer Survivors and Non-Cancer Controls: The Thinking and Living With Cancer Study
Authors: Mandelblatt Jeanne S , Zhou Xingtao , Small Brent J , Ahn Jaeil , Zhai Wanting , Ahles Tim , Extermann Martine , Graham Deena , Jacobsen Paul B , Jim Heather , McDonald Brenna C , Patel Sunita J , Root James C , Saykin Andrew J , Cohen Harvey Jay , Carroll Judith E
Published: January 2021

Background

We evaluated deficit accumulation and how deficits affected cognition and physical activity among breast cancer survivors and non-cancer controls.

Methods

Newly diagnosed nonmetastatic survivors (n = 353) and matched non-cancer controls (n = 355) ages 60-98 years without neurological impairments were assessed presystemic therapy (or at enrollment for controls) from August 2010 to December 2016 and followed for 36 months. Scores on a 42-item index were analyzed in growth-mixture models to determine deficit accumulation trajectories separately and combined for survivors and controls. Multilevel models tested associations between trajectory and cognition (FACT-Cog and neuropsychological tests) and physical activity (IPAQ-SF) for survivors and controls.

Results

Deficit accumulation scores were in the robust range, but survivors had higher scores (95% confidence intervals [CI]) than controls at 36 months (0.18, 95% CI = 0.16 to 0.19, vs 0.16, 95% CI = 0.14 to 0.17; P = .001), and averages included diverse deficit trajectories. Survivors who were robust but became frailer (8.8%) had similar baseline characteristics to those remaining robust (76.2%) but experienced a 9.6-point decline self-reported cognition (decline of 9.6 vs 3.2 points; P = .04) and a 769 MET minutes per week decline in physical activity (P < .001). Survivors who started and remained prefrail (15.0%) had self-reported and objective cognitive problems. At baseline, frail controls (9.5%) differed from robust controls (83.7%) on deficits and self-reported cognition (P < .001). Within combined trajectories, frail survivors had more sleep disturbances than frail controls (48.6% [SD = 17.4%] vs 25.0% [SD = 8.2%]; P = .05).

Conclusions

Most survivors and controls remained robust, and there were similar proportions on a frail trajectory. However, there were differences in deficit patterns between survivors and controls. Survivor deficit accumulation trajectory was associated with patient-reported outcomes. Additional research is needed to understand how breast cancer and its treatments affect deficit accumulation.
An Experimental Comparison of Three Strategies for Converting Mail Respondents in a Probability-Based Mixed-Mode Panel to Internet Respondents
Authors: Bretschi David , Schaurer Ines , Dillman Don A
Published: January 2021

In recent years, web-push strategies have been developed in cross-sectional mixed-mode surveys to improve response rates and reduce the costs of data collection. However, pushing respondents into the more cost-efficient web mode has rarely been examined in the context of panel surveys. This study evaluates how a web-push intervention affects the willingness of panel members to switch survey modes from mail to web. We tested three web-push strategies in a German probability-based mixed-mode panel by randomly assigning 1,895 panelists of the mail mode to one of three conditions: (1) the web option was offered to panelists concurrently with the paper questionnaire including a promised €10 incentive for completing the survey on the web, (2) the web option was presented sequentially two weeks before sending the paper questionnaire and respondents were also promised an incentive of €10, or (3) same sequential web-first approach as for condition 2, but with a prepaid €10 incentive instead of a promised incentive. The study found that a sequential presentation of the web option significantly increases the web response in a single survey but may not motivate more panelists to switch to the web mode permanently. Contrary to our expectation, offering prepaid incentives neither improves the web response nor the proportion of mode switchers. Overall, all three web-push strategies show the potential to effectively reduce survey costs without causing differences in panel attrition after five consecutive waves. Condition 2, the sequential web-first design combined with a promised incentive was most effective in pushing respondents to switch to the web mode and in reducing costs.
Top 10 Research Priorities for U.S. Military En Route Combat Casualty Care
Authors: Hatzfeld Jennifer J , Hildebrandt George , Maddry Joseph K , Rodriquez Dario , Bridges Elizabeth , Ritter Anne C , Gardner Cubby L , Bebarta Vikhyat S , Cap Andrew P
Published: January 2021

Introduction

Within the Military Health System, the process of transporting patients from an initial point of injury and throughout the entire continuum of care is called “en route care.” A Committee on En Route Combat Casualty Care was established in 2016 as part of the DoD Joint Trauma System to create practice guidelines, recommend training standards, and identify research priorities within the military en route care system.

Materials and Methods

Following an analysis of currently funded research, future capabilities, and findings from a comprehensive scoping study, members of a sub-working group for research identified the top research priorities that were needed to better guide evidence-based decisions for practice and policy, as well as the future state of en route care.

Results

Based on the input from the entire committee, 10 en route care research topics were rank-ordered in the following manner: (1) medical documentation, (2) clinical decision support, (3) patient monitoring, (4) transport physiology, (5) transfer of care, (6) maintaining normothermia, (7) transport timing following damage control resuscitation or surgery, (8) intelligent tasking, (9) commander’s risk assessment, and (10) unmanned transport. Specific research questions and technological development needs were further developed by committee members in an effort to guide future research and development initiatives that can directly support operational en route care needs. The research priorities reflect three common themes, which include efforts to enhance or increase care provider capability and capacity; understand the impact of transportation on patient physiology; and increase the ability to coordinate, communicate, and facilitate patient movement. Technology needs for en route care must support interoperability of medical information, equipment, and supplies across the global military health system in addition to adjusting to a dynamic transport environment with the smallest possible weight, space, and power requirements.

Conclusions

To ensure an evidence-based approach to future military conflicts and other medical challenges, focused research and technological development to address these 10 en route care research gaps are urgently needed.
The inner circumstellar dust of the red supergiant Antares as seen with VLT/SPHERE/ZIMPOL
Authors: Cannon E , Montargès M , de Koter A , Decin L , Min M , Lagadec E , Kervella P , Sundqvist J O , Sana H
Published: January 2021

The processes by which red supergiants lose mass are not fully understood thus-far and their mass-loss rates lack theoretical constraints. The ambient surroundings of the nearby M0.5 Iab star Antares offer an ideal environment to obtain detailed empirical information on the outflow properties at its onset, and hence indirectly, on the mode(s) of mass-loss. We present and analyse optical VLT/SPHERE/ZIMPOL polarimetric imaging with angular resolution down to 23 milliarcsec, sufficient to spatially resolve both the stellar disc and its direct surroundings. We detect a conspicuous feature in polarized intensity that we identify as a clump containing dust, which we characterize through 3D radiative transfer modelling. The clump is positioned behind the plane of the sky, therefore has been released from the backside of the star, and its inner edge is only 0.3 stellar radii above the surface. The current dust mass in the clump is $1.3^{+0.2}_{-1.0} \times 10^{-8} \, \mathrm{M}_{\odot }$, though its proximity to the star implies that dust nucleation is probably still ongoing. The ejection of clumps of gas and dust makes a non-negligible contribution to the total mass lost from the star that could possibly be linked to localized surface activity such as convective motions or non-radial pulsations.
Comprehensive broad-band study of accreting neutron stars with Suzaku: Is there a bi-modality in the X-ray spectrum?
Authors: Pradhan Pragati , Paul Biswajit , Bozzo Enrico , Maitra Chandreyee , Paul B C
Published: January 2021

We present a broad-band spectral analysis of accreting neutron stars using data from XIS and PIN onboard Suzaku. From spectral fits of these sources with a single continuum model including a power law and high energy cut-off, cyclotron lines (where required), we studied the correlation between various spectral parameters. Among 39 sources we studied, 16 are those where the existence of a cyclotron line is known in literature, and 29 need a cut-off energy. Among these 29 sources, 18 have cut-off energy bunched in a range of 3–10 keV while for 11 sources, it spreads over 12–25 keV. This bi-modal behaviour is not based on the specific nature of the systems being a Be XRB or supergiant HMXB, nor on different beaming patterns characterizing their X-ray emission (as inferred from simultaneous study of their pulse profiles). The broad-band coverage of Suzaku also shows that the cut-off energies saturate for higher values of cyclotron line energies – consistent with previous works in literature – for both the groups and the width of the cyclotron line show a weak correlation with the cyclotron line energy. We also find an anticorrelation with luminosity for both spectral index and folding energy, respectively. Unlike previous works, we did not detect any anticorrelation between X-ray luminosity and EW of K α lines. Finally, we show that the EW and flux of the iron K α line are smaller in SFXTs than classical NS-HMXBs. We discuss these findings in terms of different properties of stellar winds and accretion mechanisms.
The effect of jet–ejecta interaction on the viewing angle dependence of kilonova light curves
Authors: Klion Hannah , Duffell Paul C , Kasen Daniel , Quataert Eliot
Published: January 2021

The merger of two neutron stars produces an outflow of radioactive heavy nuclei. Within a second of merger, the central remnant is expected to also launch a relativistic jet, which shock-heats and disrupts a portion of the radioactive ejecta. Within a few hours, emission from the radioactive material gives rise to an ultraviolet, optical, and infrared transient (a kilonova). We use the endstates of a suite of 2D relativistic hydrodynamic simulations of jet–ejecta interaction as initial conditions for multidimensional Monte Carlo radiation transport simulations of the resulting viewing angle-dependent light curves and spectra starting at $1.5\, \mathrm{h}$ after merger. We find that on this time-scale, jet shock heating does not affect the kilonova emission for the jet parameters we survey. However, the jet disruption to the density structure of the ejecta does change the light curves. The jet carves a channel into the otherwise spheroidal ejecta, revealing the hot, inner regions. As seen from near (≲30°) the jet axis, the kilonova is brighter by a factor of a few and bluer. The strength of this effect depends on the jet parameters, since the light curves of more heavily disrupted ejecta are more strongly affected. The light curves and spectra are also more heavily modified in the ultraviolet than in the optical.
Spin evolution of neutron stars in two modes: implication for millisecond pulsars
Authors: Bhattacharyya Sudip
Published: January 2021

An understanding of spin frequency (ν) evolution of neutron stars in the low-mass X-ray binary (LMXB) phase is essential to explain the observed ν-distribution of millisecond pulsars (MSPs), and to probe the stellar and binary physics, including the possibility of continuous gravitational wave emission. Here, using numerical computations we conclude that ν can evolve in two distinctly different modes, as ν may approach a lower spin equilibrium value (νeq,per) for persistent accretion for a long-term average accretion rate ($\dot{M}_{\rm av}$) greater than a critical limit ($\dot{M}_{\rm av,crit}$), and may approach a higher effective spin equilibrium value (νeq,eff) for transient accretion for $\dot{M}_{\rm av} \lt \dot{M}_{\rm av,crit}$. For example, when $\dot{M}_{\rm av}$ falls below $\dot{M}_{\rm av,crit}$ for an initially persistent source, ν increases considerably due to transient accretion, which is counter-intuitive. We also find that, contrary to what was suggested, a fast or sudden decrease of $\dot{M}_{\rm av}$ to zero in the last part of the LMXB phase is not essential for the genesis of spin-powered MSPs, and neutron stars could spin-up in this $\dot{M}_{\rm av}$-decreasing phase. Our findings imply that the traditional way of ν-evolution computation is inadequate in most cases, even for initially persistent sources, and may not even correctly estimate whether ν increases or decreases.
Search for translation arrest peptides encoded upstream of genes for components of protein localization pathways
Authors: Sakiyama Karen , Shimokawa-Chiba Naomi , Fujiwara Keigo , Chiba Shinobu
Published: January 2021

Regulatory nascent peptides participate in the regulation of cellular functions by the mechanisms involving regulated translation arrest. A class of them in bacteria, called monitoring substrates, feedback-regulates the expression of a specific component of protein localization machinery. Three monitoring substrates, SecM, MifM and VemP have previously been identified. Here, we attempt at identifying additional arrest peptides in bacteria. Our bioinformatic searches over more than 400 bacterial genomic sequences for proteins that have the common characteristic features shared by the known monitoring substrates and subsequent in vitro and in vivo characterization of the highlighted sequences allowed the identification of three arrest peptides termed ApcA, ApdA and ApdP. ApcA and ApdA homologs are conserved among a subset of actinobacteria, whereas ApdP has homologs in a subset of α-proteobacteria. We demonstrate that these arrest peptides, in their ribosome-tethered nascent states, inhibit peptidyl transfer. The elongation arrest occurs at a specific codon near the 3′ end of the coding region, in a manner depending on the amino acid sequence of the nascent chain. Interestingly, the arrest sequences of ApcA, ApdA and ApdP share a sequence R-A-P-G/P that is essential for the elongation arrest.
COVID-19 reinfection in the presence of neutralizing antibodies
Authors: Zhang Ju , Ding Nan , Ren Lili , Song Rui , Chen Danying , Zhao Xuesen , Chen Budong , Han Junyan , Li Jiarui , Song Yangzi , Di Lin , Han Kai , Yu Fengting , Xie Ruming , Chen Zhihai , Xie Wen , Liu Jingyuan , Cen Shan , Bi Yuhai , Wu Angela R , Zhang Fujie , Chen Chen , Zeng Hui
Published: January 2021

After a short recovery period, COVID-19 reinfections could occur in convalescent patients, even those with measurable levels of neutralizing antibodies. Effective vaccinations and protective public health measures are recommended for the convalescent COVID-19 patients.
Arabidopsis casein kinase 2 triggers stem cell exhaustion under Al toxicity and phosphate deficiency through activating the DNA damage response pathway
Authors: Wei Pengliang , Demulder Manon , David Pascale , Eekhout Thomas , Yoshiyama Kaoru Okamoto , Nguyen Long , Vercauteren Ilse , Eeckhout Dominique , Galle Margot , De Jaeger Geert , Larsen Paul , Audenaert Dominique , Desnos Thierry , Nussaume Laurent , Loris Remy , De Veylder Lieven
Published: January 2021

Aluminum (Al) toxicity and inorganic phosphate (Pi) limitation are widespread chronic abiotic and mutually enhancing stresses that profoundly affect crop yield. Both stresses strongly inhibit root growth, resulting from a progressive exhaustion of the stem cell niche. Here, we report on a casein kinase 2 (CK2) inhibitor identified by its capability to maintain a functional root stem cell niche in Arabidopsis thaliana under Al toxic conditions. CK2 operates through phosphorylation of the cell cycle checkpoint activator SUPPRESSOR OF GAMMA RADIATION1 (SOG1), priming its activity under DNA-damaging conditions. In addition to yielding Al tolerance, CK2 and SOG1 inactivation prevents meristem exhaustion under Pi starvation, revealing the existence of a low Pi-induced cell cycle checkpoint that depends on the DNA damage activator ATAXIA-TELANGIECTASIA MUTATED (ATM). Overall, our data reveal an important physiological role for the plant DNA damage response pathway under agriculturally limiting growth conditions, opening new avenues to cope with Pi limitation.
Sulfur transfer from the endophytic fungus Serendipita indica improves maize growth and requires the sulfate transporter SiSulT
Authors: Narayan Om Prakash , Verma Nidhi , Jogawat Abhimanyu , Dua Meenakshi , Johri Atul Kumar
Published: January 2021

A deficiency of the essential macronutrient sulfur leads to stunted plant growth and yield loss; however, an association with a symbiotic fungus can greatly improve nutrient uptake by the host plant. Here, we identified and functionally characterized a high-affinity sulfate transporter from the endophytic fungus Serendipita indica. SiSulT fulfills all the criteria expected of a functional sulfate transporter responding to sulfur limitation: SiSulT expression was induced when S. indica was grown under low-sulfate conditions, and heterologous expression of SiSulT complemented a yeast mutant lacking sulfate transport. We generated a knockdown strain of SiSulT by RNA interference to investigate the consequences of the partial loss of this transporter for the fungus and the host plant (maize, Zea mays) during colonization. Wild-type (WT) S. indica, but not the knockdown strain (kd-SiSulT), largely compensated for low-sulfate availability and supported plant growth. Colonization by WT S. indica also allowed maize roots to allocate precious resources away from sulfate assimilation under low-sulfur conditions, as evidenced by the reduction in expression of most sulfate assimilation genes. Our study illustrates the utility of the endophyte S. indica in sulfur nutrition research and offers potential avenues for agronomically sound amelioration of plant growth in low-sulfate environments.
Endosperm development is an autonomously programmed process independent of embryogenesis
Authors: Xiong Hanxian , Wang Wei , Sun Meng-Xiang
Published: January 2021

The seeds of flowering plants contain three genetically distinct structures: the embryo, endosperm, and seed coat. The embryo and endosperm need to interact and exchange signals to ensure coordinated growth. Accumulating evidence has confirmed that embryo growth is supported by the nourishing endosperm and regulated by signals originating from the endosperm. Available data also support that endosperm development requires communication with the embryo. Here, using single-fertilization mutants, Arabidopsis thaliana dmp8 dmp9 and gex2, we demonstrate that in the absence of a zygote and embryo, endosperm initiation, syncytium formation, free nuclear cellularization, and endosperm degeneration occur as in the wild type in terms of the cytological process and time course. Although rapid embryo expansion accelerates endosperm breakdown, our findings strongly suggest that endosperm development is an autonomously organized process, independent of egg cell fertilization and embryo–endosperm communication. This work confirms both the altruistic and self-directed nature of the endosperm during coordinated embryo–endosperm development. Our findings provide insights into the intricate interaction between the two fertilization products and will help to distinguish the physiological roles of the signaling between endosperm and embryo. These findings also open new avenues in agro-biotechnology for crop improvement.
The role of GDP-l-galactose phosphorylase in the control of ascorbate biosynthesis
Authors: Fenech Mario , Amorim-Silva Vítor , Esteban del Valle Alicia , Arnaud Dominique , Ruiz-Lopez Noemi , Castillo Araceli G , Smirnoff Nicholas , Botella Miguel A
Published: January 2021

The enzymes involved in l-ascorbate biosynthesis in photosynthetic organisms (the Smirnoff–Wheeler [SW] pathway) are well established. Here, we analyzed their subcellular localizations and potential physical interactions and assessed their role in the control of ascorbate synthesis. Transient expression of C terminal-tagged fusions of SW genes in Nicotiana benthamiana and Arabidopsis thaliana mutants complemented with genomic constructs showed that while GDP-d-mannose epimerase is cytosolic, all the enzymes from GDP-d-mannose pyrophosphorylase (GMP) to l-galactose dehydrogenase (l-GalDH) show a dual cytosolic/nuclear localization. All transgenic lines expressing functional SW protein green fluorescent protein fusions driven by their endogenous promoters showed a high accumulation of the fusion proteins, with the exception of those lines expressing GDP-l-galactose phosphorylase (GGP) protein, which had very low abundance. Transient expression of individual or combinations of SW pathway enzymes in N. benthamiana only increased ascorbate concentration if GGP was included. Although we did not detect direct interaction between the different enzymes of the pathway using yeast-two hybrid analysis, consecutive SW enzymes, as well as the first and last enzymes (GMP and l-GalDH) associated in coimmunoprecipitation studies. This association was supported by gel filtration chromatography, showing the presence of SW proteins in high-molecular weight fractions. Finally, metabolic control analysis incorporating known kinetic characteristics showed that previously reported feedback repression at the GGP step, combined with its relatively low abundance, confers a high-flux control coefficient and rationalizes why manipulation of other enzymes has little effect on ascorbate concentration.
Electric quadrupole form factors of singly heavy baryons with spin 3/2
Authors: Kim June-Young , Kim Hyun-Chul
Published: January 2021

We study the electromagnetic form factors of the lowest-lying singly heavy baryons in a pion mean-field approach, which is also known as the SU(3) chiral quark-soliton model. In the limit of the heavy-quark mass, the dynamics inside a singly heavy baryon is governed by the $N_c-1$ valence quarks, while the heavy quark remains as a static one. In this framework, a singly heavy baryon is described by combining the $N_c-1$ soliton with the singly heavy quark. In the infinitely heavy-quark mass limit, we can compute the electric quadrupole form factors of the baryon sextet with spin 3/2, with the rotational $1/N_c$ and linear corrections of the explicit flavor SU(3) symmetry breaking taken into account. We find that the sea-quark contributions or the Dirac-sea level contributions dominate over the valence-quark contributions in the lower $Q^2$ region. We examined the effects of explicit flavor SU(3) symmetry breaking in detail. The numerical results are also compared with the recent data from the lattice calculation with the unphysical value of the pion mass considered, which was used in the lattice calculation.
Post-COVID syndrome and suicide risk
Authors: Sher L
Published: January 2021

A significant number of coronavirus disease SARS-CoV-2 (COVID-19) patients continue to have symptoms related to COVID-19 after the acute phase of illness. This post-COVID condition is sometimes called ‘post-COVID syndrome’, ‘long COVID’ or ‘post-acute COVID-19’. Persistent psychiatric symptoms among COVID-19 survivors such as depression, anxiety, post-traumatic symptoms and cognitive impairment may be related to psychological factors and neurobiological injury. COVID-19 related neurological symptoms including anosmia, ageusia, dizziness, headache and seizures may persist for a long time after the acute COVID-19 illness. Many COVID-19 survivors experience persistent physical symptoms such as cough, fatigue, dyspnea and pain after recovering from their initial illness. There is a high probability that symptoms of psychiatric, neurological and physical illnesses, as well as inflammatory damage to the brain in individuals with post-COVID syndrome increase suicidal ideation and behavior in this patient population. COVID-19 survivors without post-COVID syndrome may also be at elevated suicide risk. Studies of suicidality in COVID-19 survivors are urgently needed and will be a new area of suicide research. An appropriate management of psychiatric, neurological and medical conditions may reduce suicide risk among COVID-19 survivors with or without post-COVID syndrome.
High burden of infections in Indian patients with Idiopathic Inflammatory Myopathy: validation of observations from the MyoCite dataset
Authors: Chatterjee Rudrarpan , Mehta Pankti , Agarwal Vikas , Gupta Latika
Published: January 2021

Objective

To determine the prevalence, profile and predictors of infections in an Indian cohort with idiopathic inflammatory myopathies (IIM).

Methods

We reviewed the records of a retrospective cohort with IIM enrolled from consecutive patients being followed up in the clinic, and these constituted the observation cohort. A newly diagnosed inception cohort with IIM were followed prospectively as the validation cohort for confirmation of observations and comparison with the observation cohort.

Results

Among the 68 patients in the observation cohort (average age 33.4 years, female:male 4.2:1), 37 (54.4%) experienced 54 infections between them; of these 54 infections, 21 (38.8%) were major and recurrent infections and they occurred in 11 patients (16.17%) over 3.08 years. Tuberculosis was the most common infection (12, 22.2%), with a predominance of extrapulmonary forms. Serum protein [odds ratio (OR) 0.44], platelets (0.44) at disease onset and daily steroid dose (1.04) predicted major infections on multivariate analysis. A higher daily dose of steroids at first infection correlated with number of recurrent infections. The infection-free 1-year survival was 73.8%.

Of the 70 patients in the validation cohort (average age 35.7 years, female:male 3.7:1), 3 had myositis attributed to an infection. A similar proportion of the cohort experienced infections (22, 33.3%) with similar number of major (10, 45.4%) and recurrent (4, 18%) infections being recorded. The most common infection was community-acquired pneumonia, followed by tuberculosis, with serum albumin (OR 0.25) at disease onset being the only predictor. The one-year infection-free survival rate was 64.7%. Those who had a major infection had increased mortality at 1 year, with a survival rate of 60%, compared with 89.09% in those without.

In both cohorts, a daily prednisone dose >6.25 mg predisposed to major infections.

Conclusion

Major and recurrent infections are common in Indian IIM patients and confer higher risk for future infections and lower survival. Respiratory and atypical bacterial infections such as tuberculosis occur throughout the disease course.
Frugoside delays osteoarthritis progression via inhibiting miR-155-modulated synovial macrophage M1 polarization
Authors: Wang Hao , Zhang Haiyan , Fan Kai , Zhang Danyang , Hu Aihau , Zeng Xiangzhou , Liu Yan li , Tan Guanghong , Wang Hua
Published: January 2021

Objectives

Direct inhibition of M1 polarization of synovial macrophages may be a useful therapeutic treatment for OA and OA-associated synovitis. Frugoside (FGS) is a cardiac glycoside compound isolated and extracted from Calotropis gigantea. Cardiac glycosides possess interesting anti-inflammatory potential. However, the corresponding activity of FGS has not been reported. Therefore, our aim was to find direct evidence of the effects of FGS on synovial macrophage M1 polarization and OA control.

Methods

Collagenase was used to establish an experimental mouse OA model (CIOA) with considerable synovitis. Then, FGS was intra-articular administered. The mRNA and protein levels of iNOS were analysed by real-time PCR and Western blotting in vitro. Immunohistochemical and immunofluorescence staining were used to measure the expression of F4/80, iNOS, Col2α1 and MMP13 in vivo. The levels of pro-inflammatory cytokines in FGS-treated M1 macrophage culture supernatants were analysed by flow cytometry.

Results

FGS attenuates synovial inflammation and delays the development of OA in CIOA mice. Further results demonstrate that FGS inhibits macrophage M1 polarization in vitro and in vivo, which subsequently decreases the secretion of IL-6 and TNF-α, in turn delaying cartilage and extracellular matrix (ECM) degradation and chondrocyte hypertrophy. FGS inhibits macrophage M1 polarization by partially downregulating miR-155 levels.

Conclusion

This study demonstrates that intra-articular injection of FGS is a potential strategy for OA prevention and treatment, even at an early stage of disease progression. This is a novel function of FGS and has promising future clinical applications.
Are musculoskeletal conditions neglected in national health surveys?
Authors: Ferreira Giovanni E , Buchbinder Rachelle , Zadro Joshua R , O’Keeffe Mary , Kharel Priti , Carballo-Costa Lidia , Oliveira Juliana S , Maher Christopher G
Published: January 2021

Objective

To describe the proportion of national health surveys that contain questions on the prevalence and consequences of musculoskeletal conditions.

Methods

We used a comprehensive search strategy to obtain national health surveys from the 218 countries listed by the World Bank. Two authors independently extracted information from each national health survey. Outcomes were the proportion of surveys that contained questions on the prevalence of musculoskeletal conditions using the Global Burden of Disease categorization of RA, OA, low back pain, neck pain, gout and other and contained condition-specific questions about activity limitation, severity of pain and work absence. We also measured how frequently the prevalence of low back pain was measured using a consensus-based standard definition for low back pain prevalence studies.

Results

We identified national health surveys from 170 countries. Sixty-two (36.4%), the majority from high-income countries (n = 43), measured the prevalence of at least one musculoskeletal condition. OA [53 (85.4%)], low back pain [39 (62.9%)] and neck pain [37 (59.7%)] were most commonly measured, while RA and gout prevalence were only measured in 10 (5.9%) and 3 (1.8%) surveys, respectively. A minority of surveys assessed condition-specific activity limitations [6 (3.6%)], pain severity [5 (2.9%)] and work absence [1 (0.6%)]. Only one survey used the consensus-based standard definition for low back pain.

Conclusion

Musculoskeletal conditions are neglected in the majority of national health surveys. Monitoring musculoskeletal conditions through ongoing surveys is crucial for the development and evaluation of health policies to reduce their burden.
Delineating phenotypes of Kawasaki disease and SARS-CoV-2-related inflammatory multisystem syndrome: a French study and literature review
Authors: Cherqaoui Bilade , Koné-Paut Isabelle , Yager Hélène , Bourgeois Fleur Le , Piram Maryam
Published: January 2021

Objective

To better define the clinical distinctions between the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related paediatric inflammatory multisystem syndrome (PIMS) and Kawasaki disease (KD).

Methods

We compared three groups of patients: group 1, cases from our national historic KD database (KD-HIS), before the SARS-CoV-2 pandemic; group 2, patients with KD admitted to an intensive care unit (KD-ICU) from both our original cohort and the literature, before the SARS-CoV-2 pandemic; and group 3, patients with PIMS from the literature.

Results

KD-HIS included 425 patients [male:female ratio 1.3, mean age 2.8 years (s.d. 2.4)], KD-ICU 176 patients [male:female ratio 1.3, mean age 3.5 years (s.d. 3.1)] and PIMS 404 patients [male:female ratio 1.4, mean age 8.8 years (s.d. 3.7)]. As compared with KD-HIS patients, KD-ICU and PIMS patients had a higher proportion of cardiac failure, digestive and neurological signs. KD-ICU and PIMS patients also had a lower frequency of typical KD-mucocutaneous signs, lower platelet count, higher CRP and lower sodium level. As compared with KD-HIS and KD-ICU patients, PIMS patients were older and more frequently had myocarditis; they also had fewer coronary abnormalities and lower sodium levels. Unresponsiveness to IVIG was more frequent in KD-ICU than KD-HIS and PIMS patients.

Conclusion

On clinical grounds, KD-HIS, KD-ICU and PIMS might belong to a common spectrum of non-specific pathogen-triggered hyperinflammatory states. The causes of increasing inflammation severity within the three entities and the different effects on the heart remain to be determined.