bluuebunny/crossref_metadata_2025 huggingface dataset:
Chirality and the Origin of Life
Authors: Devínsky Ferdinand
Published: December 2021

The origin of life, based on the homochirality of biomolecules, is a persistent mystery. Did life begin by using both forms of chirality, and then one of the forms disappeared? Or did the choice of homochirality precede the formation of biomolecules that could ensure replication and information transfer? Is the natural choice of L-amino acids and D-sugars on which life is based deterministic or random? Is the handedness present in/of the Universe from its beginning? The whole biosystem on the Earth, all living creatures are chiral. Many theories try to explain the origin of life and chirality on the Earth: e.g., the panspermia hypothesis, the primordial soup hypothesis, theory of parity violation in weak interactions. Additionally, heavy neutrinos and the impact of the fact that only left-handed particles decay, and even dark matter, all have to be considered.
β-Delayed γ Emissions of 26P and Its Mirror Asymmetry
Authors: Jian Hao , Gao Yufeng , Dai Fanchao , Liu Jiajian , Xu Xinxing , Yuan Cenxi , Kaneko Kazunari , Sun Yang , Liang Pengfei , Shi Guozhu , Sun Lijie , Xayavong Latsamy , Lin Chengjian , Lee Jenny , Li Zhihuan , Yang Yanyun , Li Pengjie , Fan Rui , Zha Sixian , Zhu Haofan , Li Jinhai , Gao Qirui , Zhang Zhaozhan , Chen Ruofu , Wang Jiansong , Wang Dongxi , Wu Hongyi , Wang Kang , Lam Yihua , Duan Fangfang , Ma Peng , Gao Zhihao , Hu Qiang , Bai Zhen , Ma Junbing , Wang Jianguo , Zhong Fupeng , Wu Chenguang , Luo Diwen , Jiang Ying , Liu Yang , Hou Dongsheng , Li Ren , Ma Nanru , Ma Weihu , Yu Gongming , Patel Dipika , Jin Shuya , Wang Yufeng , Yu Yuechao , Zhou Qingwu , Wang Peng , Hu Liyuan , Wang Xiang , Zang Hongliang , Zhao Qingqing , Yang Lei , Wen Peiwei , Yang Feng , Jia Huiming , Zhang Gaolong , Pan Min , Wang Xiaoyu , Sun Haohan , Wang Meng , Hu Zhengguo , Zhou Xiaohong , Zhang Yuhu , Xu Hushan , Liu Minliang , Ong Hooi-Jin , Yang Weiqing
Published: December 2021

The study of the origin of asymmetries in mirror β decay is extremely important to understand the fundamental nuclear force and the nuclear structure. The experiment was performed at the National Laboratory of Heavy Ion Research Facility in Lanzhou (HIRFL) to measure the β-delayed γ rays of 26P by silicon array and Clover-type high-purity Germanium (HPGe) detectors. Combining with results from the β decay of 26P and its mirror nucleus 26Na, the mirror asymmetry parameter δ ( ≡ft+/ft−− 1) was determined to be 46(13)% for the transition feeding the first excited state in the daughter nucleus. Our independent results support the conclusion that the large mirror asymmetry is close to the proton halo structure in 26P.
How Does Spacetime “Tell an Electron How to Move”?
Authors: Ord Garnet
Published: December 2021

Minkowski spacetime provides a background framework for the kinematics and dynamics of classical particles. How the framework implements the motion of matter is not specified within special relativity. In this paper we specify how Minkowski space can implement motion in such a way that ’quantum’ propagation occurs on appropriate scales. This is done by starting in a discrete space and explicitly taking a continuum limit. The argument is direct and illuminates the special tension between ’rest’ and ’uniform motion’ found in Minkowski space, showing how the formal analytic continuations involved in Minkowski space and quantum propagation arise from the same source.
Risk-Neutral Pricing Method of Options Based on Uncertainty Theory
Authors: Huang Hong , Ning Yufu
Published: December 2021

In order to rationally deal with the belief degree, Liu proposed uncertainty theory and refined into a branch of mathematics based on normality, self-duality, sub-additivity and product axioms. Subsequently, Liu defined the uncertainty process to describe the evolution of uncertainty phenomena over time. This paper proposes a risk-neutral option pricing method under the assumption that the stock price is driven by Liu process, which is a special kind of uncertain process with a stationary independent increment. Based on uncertainty theory, the stock price’s distribution and inverse distribution function under the risk-neutral measure are first derived. Then these two proposed functions are applied to price the European and American options, and verify the parity relationship of European call and put options.
Incremental Lagrangian Relaxation Based Discrete Gate Sizing and Threshold Voltage Assignment
Authors: Mangiras Dimitrios , Dimitrakopoulos Giorgos
Published: December 2021

Timing closure remains one of the most critical challenges of a physical synthesis flow, especially when the design operates under multiple operating conditions. Even if timing is almost closed at the end of the flow, last-mile placement and routing congestion optimizations may introduce new timing violations. Correcting such violations needs minimally disruptive techniques such as threshold voltage reassignment and gate sizing that affect only marginally the placement and routing of the almost finalized design. To this end, we transform a powerful Lagrangian-relaxation-based optimizer, used for global timing optimization early in the design flow, into a practical incremental timing optimizer that corrects small timing violations with fast runtime and without increasing the area/power of the design. The proposed approach was applied to already optimized designs of the ISPD 2013 benchmarks assuming that they experience new timing violations due to local wire rerouting. Experimental results show that in single corner designs, timing is improved by more than 36% on average, using 45% less runtime. Correspondingly, in a multicorner context, timing is improved by 39% when compared to the fully-fledged version of the timing optimizer.
Stretchable Textile Yarn Based on UHF RFID Helical Tag
Authors: Benouakta Sofia , Hutu Florin Doru , Duroc Yvan
Published: December 2021

In the context of wearable technology, several techniques have been used for the fabrication of radio frequency identification (RFID) tags such as 3D printing, inkjet printing, and even embroidery. In contrast to these methods where the tag is attached to the object by using sewing or simple sticking, the E-Thread® technology is a novel assembling method allowing for the integration of the RFID tag into a textile yarn and thus makes it embeddable into the object at the fabrication stage. The current E-Thread® yarn uses a RFID tag in which the antenna is a straight half-wave dipole that makes the solution vulnerable to mechanical strains (i.e., elongation). In this paper, we propose an alternative to the current RFID yarn solution with the use of an antenna having a helical geometry that answers to the mechanical issues and keeps quite similar electrical and radiative properties with respect to the present solution. The RFID helical tag was designed and simulated taking into consideration the constraints of the manufacturing process. The helical RFID tag was then fabricated using the E-Thread® technology and experimental characterization showed that the obtained structure exhibited good performance with 10.6 m of read range in the ultra high frequency (UHF) RFID band and 10% of tolerance in terms of elongation.
Preface
Authors: Maggio Aurelio , Eleftheriou Androulla , Angastiniotis Michael , Canatan Duran , Restivo Gaetano
Published: December 2021

During the last two decades there has been a rapid and significant increase of knowledge and success in the control of Hb disorders [...]
Low kV Computed Tomography of Parenchymal Abdominal Organs—A Systematic Animal Study of Different Contrast Media Injection Protocols
Authors: Overhoff Daniel , Jost Gregor , McDermott Michael , Weber Olaf , Pietsch Hubertus , Schoenberg Stefan O. , Attenberger Ulrike
Published: December 2021

Objectives: To evaluate multiphase low kV computed tomography (CT) imaging of the abdomen with reduced contrast media (CM) dose using different injection protocols. Methods: Two injection protocols were evaluated for use with low kV (80 kV) multiphase abdominal imaging in comparison to the standard procedure acquired at 120 kV (500 mgI/kg; 5 mL/s). This evaluation was conducted in a highly standardized animal study (5 Goettingen minipigs). The low kV protocols consisted of (a) a single-flow (SF) injection with 40% reduced CM dose and injection rate (300 mgI/kg; 3 mL/s) and (b) a DualFlow (DF) injection protocol consisting of 60%/40% contrast to saline ratio administered at 5 mL/s. Dynamic CT was first performed within representative liver regions to determine optimal contrast phases, followed by evaluation of the three protocols in multiphase abdominal CT imaging. The evaluation criteria included contrast enhancement (CE) of abdominal organs and vasculature. Results: The 80 kV DF injection protocol showed similar CE of the abdominal parenchymatous organs and vessels to the 120 kV reference and the 80 kV SF protocol. Hepatic parenchyma showed comparable CT values for all contrast phases. In particular, in the portal venous parenchymal phase, the 80 kV DF protocol demonstrated higher hepatic parenchymal enhancement; however, results were statistically non-significant. Similarly, CE of the kidney, pancreas, and abdominal arterial/venous vessels showed no significant differences between injection protocols. Conclusions: Adapted SF and DF injection protocols with reduced IDR/iodine load offer the potential to calibrate optimal CM doses to the tube voltage in abdominal multiphase low kV CT imaging. The data suggest that the DF approach allows the use of predefined injection protocols and adaption of the contrast to saline ratio to an individualized kV setting and yields the potential for patient-individualized CM adaption.
Chronic Dietary Exposure of Roosters to a Glyphosate-Based Herbicide Increases Seminal Plasma Glyphosate and AMPA Concentrations, Alters Sperm Parameters, and Induces Metabolic Disorders in the Progeny
Authors: Serra Loïse , Estienne Anthony , Bourdon Guillaume , Ramé Christelle , Chevaleyre Claire , Didier Philippe , Chahnamian Marine , El Balkhi Souleiman , Froment Pascal , Dupont Joëlle
Published: December 2021

The effects of chronic dietary Roundup (RU) exposure on rooster sperm parameters, fertility, and offspring are unknown. We investigated the effects of chronic RU dietary exposure (46.8 mg kg−1 day−1 glyphosate) for 5 weeks in 32-week-old roosters (n = 5 RU-exposed and n = 5 control (CT)). Although the concentrations of glyphosate and its main metabolite AMPA (aminomethylphosphonic acid) increased in blood plasma and seminal fluid during exposure, no significant differences in testis weight and sperm concentrations were observed between RU and CT roosters. However, sperm motility was significantly reduced, associated with decreased calcium and ATP concentrations in RU spermatozoa. Plasma testosterone and oestradiol concentrations increased in RU roosters. These negative effects ceased 14 days after RU removal from the diet. Epigenetic analysis showed a global DNA hypomethylation in RU roosters. After artificial insemination of hens (n = 40) with sperm from CT or RU roosters, eggs were collected and artificially incubated. Embryo viability did not differ, but chicks from RU roosters (n = 118) had a higher food consumption, body weight and subcutaneous adipose tissue content. Chronic dietary RU exposure in roosters reduces sperm motility and increases plasma testosterone levels, growth performance, and fattening in offspring.
Rapid and Sensitive Detection of Water Toxicity Based on Photosynthetic Inhibition Effect
Authors: Chen Min , Yin Gaofang , Zhao Nanjing , Gan Tingting , Feng Chun , Gu Mengyuan , Qi Peilong , Ding Zhichao
Published: December 2021

To achieve rapid and sensitive detection of the toxicity of pollutants in the aquatic environment, a photosynthetic inhibition method with microalgae as the test organism and photosynthetic fluorescence parameters as the test endpoint was proposed. In this study, eight environmental pollutants were selected to act on the tested organism, Chlorella pyrenoidosa, including herbicides (diuron, atrazine), fungicides (fuberidazole), organic chemical raw materials (phenanthrene, phenol, p-benzoquinone), disinfectants (trichloroacetonitrile uric acid), and disinfection by-products (trichloroacetonitrile). The results showed that, in addition to specific PSII inhibitors (diuretic and atrazine), other types of pollutants could also quickly affect the photosynthetic system. The photosynthetic fluorescence parameters (Fv/Fm, Yield, α, and rP) could be used to detect the effects of pollutants on the photosynthetic system. Although the decay rate of the photosynthetic fluorescence parameters corresponding to the different pollutants was different, 1 h could be used as an appropriate toxicity exposure time. Moreover, the lowest respondent concentrations of photosynthetic fluorescence parameters to diuron, atrazine, fuberidazole, phenanthrene, P-benzoquinone, phenol, trichloroacetonitrile uric acid, and trichloroacetonitrile were 2 μg·L−1, 5 μg·L−1, 0.05 mg·L−1, 2 μg·L−1, 1.0 mg·L−1, 0.4 g·L−1, 0.1 mg·L−1, and 2.0 mg·L−1, respectively. Finally, diuron, atrazine, fuberidazole, and phenanthrene were selected for a comparison of their photosynthetic inhibition and growth inhibition. The results suggested that photosynthetic inhibition could overcome the time dependence of growth inhibition and shorten the toxic exposure time from more than 24 h to less than 1 h, or even a few minutes, while, the sensitivity of the toxicity test was not weakened. This study indicates that the photosynthetic inhibition method could be used for rapid detection of the toxicity of water pollutants and that algae fluorescence provides convenient access to toxicity data.
Isolation and Insecticidal Activity of Essential Oil from Artemisia lavandulaefolia DC. against Plutella xylostella
Authors: Huang Xing , Huang Yulin , Yang Chunyue , Liu Tiantian , Liu Xing , Yuan Haibin
Published: December 2021

Many plants show significant biological activity against pests due to their unique chemical constituents. It is important to identify effective constituents for their development and utilization as botanical pesticides. Our previous study showed that Artemisia lavandulaefolia essential oil had biological activity against Plutella xylostella. Here, we isolated and identified the constituents of essential oil from A. lavandulaefolia by silica gel column chromatography. The main constituents identified were eucalyptol and caryophyllene oxide, and they were confirmed by gas chromatography–mass spectrometry (GC–MS). Eucalyptol and caryophyllene oxide showed strong contact toxicity against P. xylostella larvae after 24 h of application (Median lethal dose, LD50 = 76.97 μL/mL and 20.71 mg/mL. Furthermore, the two active constituents against P. xylostella adults showed significant fumigant activity (Mmedian lethal concentration, LC50 = 3.25 μL/L and 1.06 mg/L, respectively. Finally, we measured the detoxification enzymes and acetylcholinesterase of the larvae treated with active constituents. The eucalyptol-treated larvae displayed enhanced carboxylesterase (CarE) and glutathione-S-transferase (GST) activities in an in vivo experiment, but it was lower for acetylcholinesterase (AchE) activity. The activities of the CarE and GST significantly decreased when exposed to caryophyllene oxide. In general, the two active constituents, eucalyptol and caryophyllene oxide, showed high insecticidal activity, which demonstrates their potential to be used as natural insecticides.
Safety and Efficacy of Collagen-Based Biological Dressings in the Management of Chronic Superficial Skin Wounds in Non-Complex Trauma: A Post-Marketing Surveillance Study
Authors: De Francesco Francesco , De Francesco Marialuisa , Riccio Michele
Published: December 2021

Biological dressings such as collagen and hyaluronic acid represent the main advanced tools that plastic surgeons, dermatologists and vulnologists use today to treat chronic wounds or ulcers that do not tend to heal. These types of dressings are important because they create a moist and physiological interface at the wound level, are of natural origin, easy to use, hypo-allergenic, economical and do not create discomfort for the patient during dressing changes. We treated 128 patients (divided into four groups based on type of dressing) with non-complex superficial chronic wounds in comparison with a traditional dressing (fitostimoline gauze or polyurethane foam). We analyzed wound characteristics, healing time, and operator and patient satisfaction. A significantly higher recovery rate was observed in the “Collagen-coated plates” treatment group compared to Standard Treatment. Additionally, a significantly higher probability of recovery was observed compared to the alternative two experimental devices (Collagen-coated plates + HA and Collagen-based spray). However, the main limitation of the randomization of this study is the presence in the “Collagen-based spray” group of localized wounds, mainly in the fingers and hand. No side effects were reported in relation to the procedures or the experimental products. Collagen may be considered as a valuable therapeutic tool in non-complex chronic wounds by virtue of its low immunogenicity, flexibility and applicability in biocompatible scaffolds, and represents driving force toward enhanced wound care.
Experiences and Lessons Learned from COVID-19 Pandemic Management in South Korea and the V4 Countries
Authors: Túri Gergő , Virág Attila
Published: December 2021

In the first year and a half of the COVID-19 pandemic, South Korea suffered significantly less social and economic damage than the V4 countries (Czech Republic, Hungary, Poland, and Slovakia) despite less stringent restrictive measures. In order to explore the causes of the phenomenon, we examined the public health policies and pandemic management of South Korea and the V4 countries and the social and economic outcomes of the measures. We identified the key factors that contributed to successful public health policies and pandemic management in South Korea by reviewing the international literature. Based on the analysis results, South Korea successfully managed the COVID-19 pandemic thanks to the appropriate combination of non-pharmaceutical measures and its advanced public health system. An important lesson for the V4 countries is that successful pandemic management requires a well-functioning surveillance system, a comprehensive testing strategy, an innovative contact tracing system, transparent government communication, and a coordinated public health system. In addition, to develop pandemic management capabilities and capacities in the V4 countries, continuous training of public health human resources, support for knowledge exchange, encouragement of research on communicable disease management, and collaboration with for-profit and non-governmental organizations are recommended.
Tracking Animal Reservoirs of Pathogenic Leptospira: The Right Test for the Right Claim
Authors: Gomard Yann , Dellagi Koussay , Goodman Steven M. , Mavingui Patrick , Tortosa Pablo
Published: December 2021

Leptospirosis is the most prevalent bacterial zoonosis worldwide and, in this context, has been extensively investigated through the One Health framework. Diagnosis of human leptospirosis includes molecular and serological tools, with the serological Microscopic Agglutination Test (MAT) still being considered as the gold standard. Mammals acting as reservoirs of the pathogen include species or populations that are able to maintain chronic infection and shed the bacteria via their urine into the environment. Animals infected by Leptospira are often identified using the same diagnosis tool as in humans, i.e., serological MAT. However, this tool may lead to misinterpretations as it can signal previous infection but does not provide accurate information regarding the capacity of animals to maintain chronic infection and, hence, participate in the transmission cycle. We employ in this paper previously published data and present original results on introduced and endemic small mammals from Indian Ocean islands to show that MAT should not be used for the identification of Leptospira reservoirs. By contrast, serological data are informative on the level of exposure of animals living in a specific environment. We present a sequential methodology to investigate human leptospirosis in the One Health framework that associates molecular detection in humans and animals, together with MAT of human samples using Leptospira isolates obtained from reservoir animals occurring in the same environment.
Correction: Godzieba, D.A.; Radice, D. High-Order Multipole and Binary Love Number Universal Relations. Universe 2021, 7, 368
Authors: Godzieba Daniel A. , Radice David
Published: December 2021

The authors wish to make the following corrections to their paper [...]
Magnetic Dual Chiral Density Wave: A Candidate Quark Matter Phase for the Interior of Neutron Stars
Authors: Ferrer Efrain J. , de la Incera Vivian
Published: December 2021

In this review, we discuss the physical characteristics of the magnetic dual chiral density wave (MDCDW) phase of dense quark matter and argue why it is a promising candidate for the interior matter phase of neutron stars. The MDCDW condensate occurs in the presence of a magnetic field. It is a single-modulated chiral density wave characterized by two dynamically generated parameters: the fermion quasiparticle mass m and the condensate spatial modulation q. The lowest-Landau-level quasiparticle modes in the MDCDW system are asymmetric about the zero energy, a fact that leads to the topological properties and anomalous electric transport exhibited by this phase. The topology makes the MDCDW phase robust against thermal phonon fluctuations, and as such, it does not display the Landau–Peierls instability, a staple feature of single-modulated inhomogeneous chiral condensates in three dimensions. The topology is also reflected in the presence of the electromagnetic chiral anomaly in the effective action and in the formation of hybridized propagating modes known as axion-polaritons. Taking into account that one of the axion-polaritons of this quark phase is gapped, we argue how incident γ-ray photons can be converted into gapped axion-polaritons in the interior of a magnetar star in the MDCDW phase leading the star to collapse, a phenomenon that can serve to explain the so-called missing pulsar problem in the galactic center.
De Sitter Holography: Fluctuations, Anomalous Symmetry, and Wormholes
Authors: Susskind Leonard
Published: December 2021

The Goheer–Kleban–Susskind no-go theorem says that the symmetry of de Sitter space is incompatible with finite entropy. The meaning and consequences of the theorem are discussed in light of recent developments in holography and gravitational path integrals. The relation between the GKS theorem, Boltzmann fluctuations, wormholes, and exponentially suppressed non-perturbative phenomena suggests that the classical symmetry between different static patches is broken and that eternal de Sitter space—if it exists at all—is an ensemble average.
An Integrated System for Urban Parks Touring and Management
Authors: Pristouris Kostis , Nakos Harry , Stavrakas Yannis , Kotsopoulos Konstantinos I. , Alexandridis Theofanis , Barda Myrto S. , Ferentinos Konstantinos P.
Published: December 2021

Urban parks are important recreational spaces of environmental interest for citizens and city visitors. Targeted and attractive promotion of these areas can help develop alternative forms of “green tourism” and increase environmental awareness among citizens, which is particularly important and vital for the future of the planet. New technologies are a key tool for improving the experience of touring urban parks, as they can make the tour much more attractive by highlighting interesting information about the flora and fauna of the park, as well as various other points of interest. This paper presents an integrated system based on augmented reality, artificial intelligence, and data analytics methodologies, comprising both mobile and web applications, focusing on urban parks touring and management, respectively. Through the mobile app for the park visitors, an attractive, interactive touring environment is created which highlights the environmental and historical interest of those areas. At the same time, the web applications for the park managers receive and analyze visitor data to help improve the visitor experience and the overall quality of the park. Finally, the developed integrated system is evaluated to ensure that it meets all user requirements and that its usability and functional components satisfy both groups of potential users, i.e., park visitors and park managers.
Legacy of Plant Virology in Croatia—From Virus Identification to Molecular Epidemiology, Evolution, Genomics and Beyond
Authors: Škorić Dijana , Černi Silvija , Ćurković-Perica Mirna , Ježić Marin , Krajačić Mladen , Šeruga Musić Martina
Published: December 2021

This paper showcases the development of plant virology in Croatia at the University of Zagreb, Faculty of Science, from its beginning in the 1950s until today, more than 70 years later. The main achievements of the previous and current group members are highlighted according to various research topics and fields. Expectedly, some of those accomplishments remained within the field of plant virology, but others make part of a much-extended research spectrum exploring subviral pathogens, prokaryotic plant pathogens, fungi and their viruses, as well as their interactions within ecosystems. Thus, the legacy of plant virology in Croatia continues to contribute to the state of the art of microbiology far beyond virology. Research problems pertinent for directing the future research endeavors are also proposed in this review.
Role of Damage-Associated Molecular Pattern/Cell Death Pathways in Vaccine-Induced Immunity
Authors: Lee Sun Min , Kim Paul , You Jinsuh , Kim Eui Ho
Published: December 2021

Immune responses induced by natural infection and vaccination are known to be initiated by the recognition of microbial patterns by cognate receptors, since microbes and most vaccine components contain pathogen-associated molecular patterns. Recent discoveries on the roles of damage-associated molecular patterns (DAMPs) and cell death in immunogenicity have improved our understanding of the mechanism underlying vaccine-induced immunity. DAMPs are usually immunologically inert, but can transform into alarming signals to activate the resting immune system in response to pathogenic infection, cellular stress and death, or tissue damage. The activation of DAMPs and cell death pathways can trigger local inflammation, occasionally mediating adaptive immunity, including antibody- and cell-mediated immune responses. Emerging evidence indicates that the components of vaccines and adjuvants induce immunogenicity via the stimulation of DAMP/cell death pathways. Furthermore, strategies for targeting this pathway to enhance immunogenicity are being investigated actively. In this review, we describe various DAMPs and focus on the roles of DAMP/cell death pathways in the context of vaccines for infectious diseases and cancer.
Molecular Basis of Epstein–Barr Virus Latency Establishment and Lytic Reactivation
Authors: Murata Takayuki , Sugimoto Atsuko , Inagaki Tomoki , Yanagi Yusuke , Watanabe Takahiro , Sato Yoshitaka , Kimura Hiroshi
Published: December 2021

Epstein–Barr virus (EBV) is a causative agent of infectious mononucleosis and several types of cancer. Like other herpesviruses, it establishes an asymptomatic, life-long latent infection, with occasional reactivation and shedding of progeny viruses. During latency, EBV expresses a small number of viral genes, and exists as an episome in the host–cell nucleus. Expression patterns of latency genes are dependent on the cell type, time after infection, and milieu of the cell (e.g., germinal center or peripheral blood). Upon lytic induction, expression of the viral immediate-early genes, BZLF1 and BRLF1, are induced, followed by early gene expression, viral DNA replication, late gene expression, and maturation and egress of progeny virions. Furthermore, EBV reactivation involves more than just progeny production. The EBV life cycle is regulated by signal transduction, transcription factors, promoter sequences, epigenetics, and the 3D structure of the genome. In this article, the molecular basis of EBV latency establishment and reactivation is summarized.
Hydroxypropyl Methylcellulose-Based Nasal Sprays Effectively Inhibit In Vitro SARS-CoV-2 Infection and Spread
Authors: Bentley Kirsten , Stanton Richard J.
Published: December 2021

The ongoing coronavirus disease (COVID-19) pandemic has required a variety of non-medical interventions to limit the transmission of the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). One such option is over-the-counter nasal sprays that aim to block virus entry and transmission within the nasal cavity. In this study, we assessed the ability of three hydroxypropyl methylcellulose (HPMC)-based powder nasal sprays, produced by Nasaleze, to inhibit SARS-CoV-2 infection and release in vitro. Upon application, the HPMC powder forms a gel-like matrix within the nasal cavity—a process we recapitulated in cell culture. We found that virus release from cells previously infected with SARS-CoV-2 was inhibited by the gel matrix product in a dose-dependent manner, with virus levels reduced by >99.99% over a 72 h period at a dose of 6.4 mg/3.5 cm2. We also show that the pre-treatment of cells with product inhibited SARS-CoV-2 infection, independent of the virus variant. The primary mechanism of action appears to be via the formation of a physical, passive barrier. However, the addition of wild garlic provided additional direct antiviral properties in some formulations. We conclude that HPMC-based nasal sprays may offer an additional component to strategies to limit the spread of respiratory viruses, including SARS-CoV-2.
Investigation of P1/HC-Pro-Mediated ABA/Calcium Signaling Responses via Gene Silencing through High- and Low-Throughput RNA-seq Approaches
Authors: Chiu Yen-Hsin , Hung Yu-Ling , Wang Hsin-Ping , Wei Wei-Lun , Shang Qian-Wen , Pham Thanh Ha , Huang Chien-Kang , Pan Zhao-Jun , Lin Shih-Shun
Published: December 2021

The P1/HC-Pro viral suppressor of potyvirus suppresses posttranscriptional gene silencing (PTGS). The fusion protein of P1/HC-Pro can be cleaved into P1 and HC-Pro through the P1 self-cleavage activity, and P1 is necessary and sufficient to enhance PTGS suppression of HC-Pro. To address the modulation of gene regulatory relationships induced by turnip mosaic virus (TuMV) P1/HC-Pro (P1/HC-ProTu), a comparative transcriptome analysis of three types of transgenic plants (P1Tu, HC-ProTu, and P1/HC-ProTu) were conducted using both high-throughput (HTP) and low-throughput (LTP) RNA-Seq strategies. The results showed that P1/HC-ProTu disturbed the endogenous abscisic acid (ABA) accumulation and genes in the signaling pathway. Additionally, the integrated responses of stress-related genes, in particular to drought stress, cold stress, senescence, and stomatal dynamics, altered the expressions by the ABA/calcium signaling. Crosstalk among the ABA, jasmonic acid, and salicylic acid pathways might simultaneously modulate the stress responses triggered by P1/HC-ProTu. Furthermore, the LTP network analysis revealed crucial genes in common with those identified by the HTP network in this study, demonstrating the effectiveness of the miniaturization of the HTP profile. Overall, our findings indicate that P1/HC-ProTu-mediated suppression in RNA silencing altered the ABA/calcium signaling and a wide range of stress responses.
Heterologous Immunity of Virus-Specific T Cells Leading to Alloreactivity: Possible Implications for Solid Organ Transplantation
Authors: Karahan Gonca E. , Claas Frans H. J. , Heidt Sebastiaan
Published: December 2021

Exposure of the adaptive immune system to a pathogen can result in the activation and expansion of T cells capable of recognizing not only the specific antigen but also different unrelated antigens, a process which is commonly referred to as heterologous immunity. While such cross-reactivity is favourable in amplifying protective immune responses to pathogens, induction of T cell-mediated heterologous immune responses to allo-antigens in the setting of solid organ transplantation can potentially lead to allograft rejection. In this review, we provide an overview of murine and human studies investigating the incidence and functional properties of virus-specific memory T cells cross-reacting with allo-antigens and discuss their potential relevance in the context of solid organ transplantation.
Brevinin-2GHk, a Peptide Derived from the Skin of Fejervarya limnocharis, Inhibits Zika Virus Infection by Disrupting Viral Integrity
Authors: Xiong Weichen , Li Jingyan , Feng Yifei , Chai Jinwei , Wu Jiena , Hu Yunrui , Tian Maolin , Lu Wancheng , Xu Xueqing , Zou Min
Published: December 2021

Several years have passed since the Zika virus (ZIKV) pandemic reoccurred in 2015–2016. However, there is still a lack of proved protective vaccines or effective drugs against ZIKV. The peptide brevinin-2GHk (BR2GK), pertaining to the brevinin-2 family of antimicrobial peptides, has been reported to exhibit only weak antibacterial activity, and its antiviral effects have not been investigated. Thus, we analyzed the effect of BR2GK on ZIKV infection. BR2GK showed significant inhibitory activity in the early and middle stages of ZIKV infection, with negligible cytotoxicity. Furthermore, BR2GK was suggested to bind with ZIKV E protein and disrupt the integrity of the envelope, thus directly inactivating ZIKV. In addition, BR2GK can also penetrate the cell membrane, which may contribute to inhibition of the middle stage of ZIKV infection. BR2GK blocked ZIKV E protein expression with an IC50 of 3.408 ± 0.738 μΜ. In summary, BR2GK was found to be a multi-functional candidate and a potential lead compound for further development of anti-ZIKV drugs.
The 21st Annual Meeting of the Rocky Mountain Virology Association
Authors: St Clair Laura A. , Brehm Ali L. , Cagle Shelby , Dunham Tillie , Faris Jonathan , Gendler Paul , Graham Monica E. , Quackenbush Sandra L. , Rovnak Joel , Perera Rushika
Published: December 2021

Nestled within the Rocky Mountain National Forest, 114 scientists and students gathered at Colorado State University’s Mountain Campus for this year’s 21st annual Rocky Mountain National Virology Association meeting. This 3-day retreat consisted of 31 talks and 30 poster presentations discussing advances in research pertaining to viral and prion diseases. The keynote address provided a timely discussion on zoonotic coronaviruses, lessons learned, and the path forward towards predicting, preparing, and preventing future viral disease outbreaks. Other invited speakers discussed advances in SARS-CoV-2 surveillance, molecular interactions involved in flavivirus genome assembly, evaluation of ethnomedicines for their efficacy against infectious diseases, multi-omic analyses to define risk factors associated with long COVID, the role that interferon lambda plays in control of viral pathogenesis, cell-fusion-dependent pathogenesis of varicella zoster virus, and advances in the development of a vaccine platform against prion diseases. On behalf of the Rocky Mountain Virology Association, this report summarizes select presentations.
Release of HSV-1 Cell-Free Virions: Mechanisms, Regulation, and Likely Role in Human-Human Transmission
Authors: Rice Stephen A.
Published: December 2021

Herpes simplex virus type 1, or HSV-1, is a widespread human pathogen that replicates in epithelial cells of the body surface and then establishes latent infection in peripheral neurons. When HSV-1 replicates, viral progeny must be efficiently released to spread infection to new target cells. Viral spread occurs via two major routes. In cell-cell spread, progeny virions are delivered directly to cellular junctions, where they infect adjacent cells. In cell-free release, progeny virions are released into the extracellular milieu, potentially allowing the infection of distant cells. Cell-cell spread of HSV-1 has been well studied and is known to be important for in vivo infection and pathogenesis. In contrast, HSV-1 cell-free release has received less attention, and its significance to viral biology is unclear. Here, I review the mechanisms and regulation of HSV-1 cell-free virion release. Based on knowledge accrued in other herpesviral systems, I argue that HSV-1 cell-free release is likely to be tightly regulated in vivo. Specifically, I hypothesize that this process is generally suppressed as the virus replicates within the body, but activated to high levels at sites of viral reactivation, such as the oral mucosa and skin, in order to promote efficient transmission of HSV-1 to new human hosts.
RIPK1 Is Cleaved by 3C Protease of Rhinovirus A and B Strains and Minor and Major Groups
Authors: Croft Sarah N. , Walker Erin J. , Ghildyal Reena
Published: December 2021

Rhinoviruses (RV), like many other viruses, modulate programmed cell death to their own advantage. The viral protease, 3C has an integral role in the modulation, and we have shown that RVA-16 3C protease cleaves Receptor-interacting protein kinase-1 (RIPK1), a key host factor that modulates various cell death and cell survival pathways. In the current study, we have investigated whether this cleavage is conserved across selected RV strains. RIPK1 was cleaved in cells infected with strains representing diversity across phylogenetic groups (A and B) and receptor usage (major and minor groups). The cleavage was abrogated in the presence of the specific 3C protease inhibitor, Rupintrivir. Interestingly, there appears to be involvement of another protease (maybe 2A protease) in RIPK1 cleavage in strains belonging to genotype B. Our data show that 3C protease from diverse RV strains cleaves RIPK1, highlighting the importance of the cleavage to the RV lifecycle.
Unfolding the Mild to Moderate Short-Term Side Effects of Four COVID-19 Vaccines Used in Bahrain: A Cross-Sectional Study
Authors: Zahid Muhammad Nauman
Published: December 2021

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) created a global pandemic (COVID-19) that has resulted in massive health and economic losses. The current unavailability of treatments leaves vaccination as the only way to control this disease. There are four vaccines (Sinopharm, Pfizer—BioNTech, Sputnik, and AstraZeneca) available in Bahrain. This project aimed to study the most common side effects resulting from the first and second doses of these four vaccines. Data were collected through an online questionnaire answered by 311 individuals who received both doses of one of these four vaccines. The results of this study revealed that regardless of the vaccine identity, participants experienced more side effects from the second dose. Among the different side effects, pain at the site of injection was primarily observed after the first dose of the Pfizer vaccine (43%), which was followed by the AstraZeneca vaccine (31%). Moreover, fever was observed in participants after the first dose of the Sputnik vaccine (37%), while headache was mainly observed after the first dose of the Pfizer vaccine (32%). It is important to note that fatigue was observed after the first dose of all four vaccines but was reported by the highest proportion of respondents in the Pfizer group (28%). Interestingly, there are some side effects, such as pain at the site of injection, that are correlated with fever (r = 0.909). Similarly, headache is correlated with fever (r = 0.801) and pain at the site of injection (r = 0.868). Overall, it was observed that recipients of the Sinopharm vaccine reported the mildest side effects among all four vaccines. The crucial finding of this study is that the first and second dosage post-vaccination side effects were modest and predictable with no occurrences of hospitalization; this information can assist in lessening vaccine apprehension.
Patients’ Perception and Knowledge about Influenza and Pneumococcal Vaccination during the COVID-19 Pandemic: An Online Survey in Patients at Risk of Infections
Authors: Loubet Paul , Rouvière Jalini , Merceron Adeline , Launay Odile , Sotto Albert ,   on behalf of the AVNIR Group
Published: December 2021

Introduction: The objective of our study was to assess, in an at-risk population, perception and knowledge about influenza and pneumococcal vaccinations. Methods: An anonymous web-based survey was submitted to patients recruited in France, from both an Ipsos internal panel and AVNIR patient associations. The study was conducted between July and October 2020, in the context of the COVID-19 pandemic. Results: Overall, 2177 questionnaires from patients at risk of infection were analyzed. Almost all respondents (86%, 1869/2177) declared themselves to be favorable to vaccination. Nearly half of the patients (49%, 1069/2177) were aware of which vaccine was recommended for their specific situation. This percentage was significantly (p < 0.001) higher for members of a patient association and for people affected by multiple chronic conditions and varied according to the type of condition. Almost two-thirds of patients (1373/2177) declared having been vaccinated during the 2019/2020 influenza season, and 41% (894/2177) were certain about being up to date with the pneumococcal vaccination. The main barriers to vaccination for influenza are the fear of side effects, doubt regarding the efficacy of the vaccine and for pneumococcal vaccination, and the absence of suggestions by the healthcare professionals (HCPs), as 64% of respondents were not recommended to obtain pneumococcal vaccination. To improve vaccine coverage, information is of prime importance and GPs are recognized as the main HCP to inform about vaccination. Nearly two-thirds (62%, 1360/2177) of patients declared that the COVID-19 pandemic convinced them to have all the recommended vaccines. Conclusion: Our study highlighted the nonoptimal vaccine coverage in at-risk populations despite a highly positive perception of vaccines and confirmed that physicians are on the front lines to suggest and recommend these vaccinations, especially in the current pandemic context, which may be used to promote other vaccines.
PICK-ing Malaysia’s Epidemic Apart: Effectiveness of a Diverse COVID-19 Vaccine Portfolio
Authors: Suah Jing Lian , Tok Peter Seah Keng , Ong Su Miin , Husin Masliyana , Tng Boon Hwa , Sivasampu Sheamini , Thevananthan Thevesh , Appannan Maheshwara Rao , Muhamad Zin Faizah , Mohd Zin Shahanizan , Yahaya Hazlina , Rusli Norhayati , Ujang Mohd Fikri , Mohd Ibrahim Hishamshah , Abdullah Noor Hisham , Peariasamy Kalaiarasu M.
Published: December 2021

Malaysia rolled out a diverse portfolio of predominantly three COVID-19 vaccines (AZD1222, BNT162b2, and CoronaVac) beginning 24 February 2021. We evaluated vaccine effectiveness with two methods, covering 1 April to 15 September 2021: (1) the screening method for COVID-19 (SARS-CoV-2) infection and symptomatic COVID-19; and (2) a retrospective cohort of confirmed COVID-19 cases for COVID-19 related ICU admission and death using logistic regression. The screening method estimated partial vaccination to be 48.8% effective (95% CI: 46.8, 50.7) against COVID-19 infection and 33.5% effective (95% CI: 31.6, 35.5) against symptomatic COVID-19. Full vaccination is estimated at 87.8% effective (95% CI: 85.8, 89.7) against COVID-19 infection and 85.4% effective (95% CI: 83.4, 87.3) against symptomatic COVID-19. Among the cohort of confirmed COVID-19 cases, partial vaccination with any of the three vaccines is estimated at 31.3% effective (95% CI: 28.5, 34.1) in preventing ICU admission, and 45.1% effective (95% CI: 42.6, 47.5) in preventing death. Full vaccination with any of the three vaccines is estimated at 79.1% effective (95% CI: 77.7, 80.4) in preventing ICU admission and 86.7% effective (95% CI: 85.7, 87.6) in preventing deaths. Our findings suggest that full vaccination with any of the three predominant vaccines (AZD1222, BNT162b2, and CoronaVac) in Malaysia has been highly effective in preventing COVID-19 infection, symptomatic COVID-19, COVID-19-related ICU admission, and death.
Potentiation of Recombinant NP and M1-Induced Cellular Immune Responses and Protection by Physical Radiofrequency Adjuvant
Authors: Li Yibo , Li Zhuofan , Zhao Yiwen , Chen Xinyuan
Published: December 2021

Nucleoprotein (NP) and matrix protein 1 (M1) are highly conserved among influenza A viruses and have been attractive targets to develop vaccines to elicit cross-reactive cytotoxic T lymphocytes (CTLs). Yet, external antigens are often presented on major histocompatibility complex class II molecules and elicit humoral immune responses. In this study, we present a physical radiofrequency adjuvant (RFA) to assist recombinant NP and M1 to elicit potent CTL responses. We found recombinant NP/M1 immunization in the presence of RFA could elicit potent anti-NP CTLs and confer significant protection against homologous viral challenges, while NP/M1 immunization alone failed to elicit significant CTL responses or confer significant protection. Interestingly, RFA failed to elicit potent anti-M1 CTL responses or anti-NP or anti-M1 antibody responses. Different from RFA, AddaVax adjuvant was found to significantly increase NP-specific antibody responses but not CTLs. NP/M1 immunization in the presence of RFA or AddaVax similarly reduced body weight loss, while only the former significantly increased the survival. We further found NP/M1 immunization in the presence of RFA did not significantly increase serum IL-6 release (a systemic inflammatory mediator) and rather reduced serum IL-6 release after boost immunization. NP/M1 immunization in the presence of RFA did not induce significant local reactions or increase body temperature of mice. The high potency and safety strongly support further development of RFA-based recombinant NP/M1 vaccine to elicit cross-protective immunity.
Receptor-Binding Domain Proteins of SARS-CoV-2 Variants Elicited Robust Antibody Responses Cross-Reacting with Wild-Type and Mutant Viruses in Mice
Authors: Shi Juan , Jin Xiaoxiao , Ding Yan , Liu Xiaotao , Shen Anran , Wu Yandan , Peng Min , Shen Chuanlai
Published: December 2021

Multiple variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have spread around the world, but the neutralizing effects of antibodies induced by the existing vaccines have declined, which highlights the importance of developing vaccines against mutant virus strains. In this study, nine receptor-binding domain (RBD) proteins of the SARS-CoV-2 variants (B.1.1.7, B.1.351 and P.1 lineages) were constructed and fused with the Fc fragment of human IgG (RBD-Fc). These RBD-Fc proteins contained single or multiple amino acid substitutions at prevalent mutation points of spike protein, which enabled them to bind strongly to the polyclonal antibodies specific for wild-type RBD and to the recombinant human ACE2 protein. In the BALB/c, mice were immunized with the wild-type RBD-Fc protein first and boosted twice with the indicated mutant RBD-Fc proteins later. All mutant RBD-Fc proteins elicited high-level IgG antibodies and cross-neutralizing antibodies. The RBD-Fc proteins with multiple substitutions tended to induce higher antibody titers and neutralizing-antibody titers than the single-mutant RBD-Fc proteins. Meanwhile, both wild-type RBD-Fc protein and mutant RBD-Fc proteins induced significantly decreased neutralization capacity to the pseudovirus of B.1.351 and P.1 lineages than to the wild-type one. These data will facilitate the design and development of RBD-based subunit vaccines against SARS-COV-2 and its variants.