Toxicity Equivalency Factors for Tetrodotoxin Analogues Determined with Automated Patch Clamp on Voltage-Gated Sodium Channels in Neuro-2a Cells.

Tetrodotoxin (TTX) is a potent marine neurotoxin, responsible for numerous poisoning incidents and some human fatalities. To date, more than 30 TTX analogues have been identified, but their individual toxicities and roles in poisoning remain largely unknown. In this work, the toxicity equivalency factors (TEFs) of five TTX analogues were determined by assessing the blockade of voltage-gated sodium channels in Neuro-2a cells using automated patch clamp (APC). All TTX analogues were less toxic than TTX. The derived TEFs were applied to the individual TTX analogues concentrations measured in pufferfish samples, using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). A comparison of these results with those obtained from APC analysis demonstrated that TEFs can be effectively used to translate LC-MS/MS analytical data into meaningful toxicological information. This is the first study to utilize APC device for the toxicological assessment of TTX analogues, highlighting its potential as a bioanalytical tool for seafood safety management and human health protection.

Analysis of the Formation of Scientific Communities in the Journal Research and Education in Nursing (2010 - 2020) and its Disciplinary Influence: an Approach from Bibliometric Analysis, Network Analysis, and Natural Language Processing.

Objective: This work sought to identify the academic communities that have shown interest and participation in the Journal Research and Education in Nursing and analyze the scientific impact generated by said journal. Methods: A bibliometric analysis was carried out, as well as social network analysis and techniques of natural language processing to conduct the research. The data was gathered and analyzed during a specific study period, covering from 2010 - 2020, for articles published in the journal, and 2010 - 2022, for articles that cited the journal within Scopus. These methods permitted performing an exhaustive evaluation of the journal's influence and reach in diverse academic and geographic contexts. Results: During the analysis, it was noted that the journal Research and Education in Nursing has had significant influence in academic and scientific communities, both nationally and internationally. Collaboration networks were detected among diverse institutions and countries, which indicates active interaction in the field of nursing research. In addition, trends and emerging patterns were identified in this field, providing a more complete view of the discipline's evolution. Conclusion: Based on the results obtained, it is concluded that the journal Research and Education in Nursing has played un fundamental role in disseminating knowledge and promoting research in nursing. The combination of Bibliometric metrics, social network analysis, and natural language processing permitted utmost comprehension of its impact in the scientific and academic community globally.

Analysis of the Formation of Scientific Communities in the Journal Research and Education in Nursing (2010 - 2020) and its Disciplinary Influence: an Approach from Bibliometric Analysis, Network Analysis, and Natural Language Processing / Análisis de la formación de comunidades científicas en la revista Investigación y Educación en Enfermería(2010-2020) y su influencia disciplinar: Un enfoque desde el análisis bibliométrico, análisis de redes y procesamiento de lenguaje natural / Análise da formação de comunidades científicas na revista Nursing Research and Education (2010-2020) e sua influência disciplinar: Uma abordagem a partir da análise bibliométrica, análise de redes e processamento de linguagem natural

Objectives. This work sought to identify the academic communities that have shown interest and participation in the Journal Research and Education in Nursing and analyze the scientific impact generated by said journal. Methods. A bibliometric analysis was carried out, as well as social network analysis and techniques of natural language processing to conduct the research. The data was gathered and analyzed during a specific study period, covering from 2010 - 2020, for articles published in the journal, and 2010 - 2022, for articles that cited the journal within Scopus. These methods permitted performing an exhaustive evaluation of the journal's influence and reach in diverse academic and geographic contexts. Results. During the analysis, it was noted that the journal Research and Education in Nursing has had significant influence in academic and scientific communities, both nationally and internationally. Collaboration networks were detected among diverse institutions and countries, which indicates active interaction in the field of nursing research. In addition, trends and emerging patterns were identified in this field, providing a more complete view of the discipline's evolution. Conclusion. Based on the results obtained, it is concluded that the journal Research and Education in Nursing has played un fundamental role in disseminating knowledge and promoting research in nursing. The combination of Bibliometric metrics, social network analysis, and natural language processing permitted utmost comprehension of its impact in the scientific and academic community globally.

Objetivos. Identificar las comunidades académicas que han mostrado interés y participación en la revista Investigación y Educación en Enfermería y analizar el impacto científico generado por esta publicación. Métodos. Se realizó un análisis bibliométrico, así como análisis de redes sociales y técnicas de procesamiento de lenguaje natural para llevar a cabo la investigación. Los datos se recopilaron y analizaron durante un período de estudio específico, abarcando los años 2010-2020, para los artículos publicados en la revista, y 2010-2022, para los artículos que citaron la revista dentro de Scopus. Estos métodos permitieron realizar una evaluación exhaustiva de la influencia y alcance de la revista en diversos contextos académicos y geográficos. Resultados. Durante el análisis, se observó que la revista Investigación y Educación en Enfermería ha ejercido una influencia significativa en las comunidades académicas y científicas, tanto a nivel nacional como internacional. Se detectaron redes de colaboración entre diversas instituciones y países, lo que indica una interacción activa en el ámbito de la investigación en enfermería. Además, se identificaron tendencias y patrones emergentes en este campo, proporcionando una visión más completa de la evolución de la disciplina. Conclusión. Basándose en los resultados obtenidos, se concluye que la revista Investigación y Educación en Enfermería ha desempeñado un papel fundamental en la difusión del conocimiento y la promoción de la investigación en enfermería. La combinación de métricas bibliométricas, análisis de redes sociales y procesamiento de lenguaje natural permitió una comprensión más completa de su impacto en la comunidad científica y académica a nivel global.

Objetivos. Identificar as comunidades acadêmicas que demonstraram interesse e participação na revista Nursing Research and Education e analisar o impacto científico gerado por esta publicação colombiana. Métodos. Foi realizada análise bibliométrica, análise de redes sociais e técnicas de processamento de linguagem natural para a realização da pesquisa. Os dados foram coletados e analisados durante um período específico de estudo, abrangendo os anos 2010-2020, para artigos publicados na revista, e 2010-2022, para artigos que citaram a revista dentro do Scopus. Esses métodos permitiram uma avaliação abrangente da influência e do alcance da revista em diversos contextos acadêmicos e geográficos. Resultados. Durante a análise, observou-se que a revista Nursing Research and Education tem exercido influência significativa nas comunidades acadêmica e científica, tanto nacional quanto internacionalmente. Foram detectadas redes de colaboração entre diversas instituições e países, o que indica interação ativa no campo da pesquisa em enfermagem. Além disso, foram identificadas tendências e padrões emergentes neste campo, proporcionando uma visão mais completa da evolução da disciplina. Conclusão. Com base nos resultados obtidos, conclui-se que a revista Nursing Research and Education tem desempenhado um papel fundamental na divulgação do conhecimento e na promoção da investigação em enfermagem. A combinação de métricas bibliométricas, análise de redes sociais e processamento de linguagem natural permitiu uma compreensão mais completa do seu impacto na comunidade científica e académica global.

Effects on Biochemical Parameters and Animal Welfare of Dusky Grouper (Epinephelus marginatus, Lowe 1834) by Feeding CTX Toxic Flesh.

Ciguatera is a foodborne disease caused by ciguatoxins (CTXs), produced by dinoflagellates (genera Gambierdiscus and Fukuyoa), which bioaccumulate in fish through the food web, causing poisoning in humans. Currently, the physiological mechanisms of the species with the highest amount of toxins in their adult stage of life that are capable of causing these poisonings are poorly understood. Dusky grouper (Epinephelus marginatus) is a relevant fishing species and is part of the CTX food chain in the Canary Islands. This study developed an experimental model of dietary exposure featuring adult dusky groupers with two diets of tissue naturally contaminated with CTXs (amberjack and moray eel flesh) with two different potential toxicities; both groups were studied at different stages of exposure (4, 6, 10, 12, and 18 weeks). The results showed that this species did not show changes in its behavior due to the provided feeding, but the changes were recorded in biochemical parameters (mainly lipid and hepatic metabolism) that may respond to liver damage and alterations in the homeostasis of the fish; more research is needed to understand histopathological and cytotoxic changes.

Nuclear quantum effects on the vibrational dynamics of the water-air interface.

We have applied path-integral molecular dynamics simulations to investigate the impact of nuclear quantum effects on the vibrational dynamics of water molecules at the water-air interface. The instantaneous fluctuations in the frequencies of the O-H stretch modes are calculated using the wavelet method of time series analysis, while the time scales of vibrational spectral diffusion are determined from frequency-time correlation functions and joint probability distributions. We find that the inclusion of nuclear quantum effects leads not only to a redshift in the vibrational frequency distribution by about 120 cm-1 for both the bulk and interfacial water molecules but also to an acceleration of the vibrational dynamics at the water-air interface by as much as 35%. In addition, a blueshift of about 45 cm-1 is seen in the vibrational frequency distribution of interfacial water molecules compared to that of the bulk. Furthermore, the dynamics of water molecules beyond the topmost molecular layer was found to be rather similar to that of bulk water.

Impact of Methylthioxylose Substituents on the Biological Activities of Lipomannan and Lipoarabinomannan in Mycobacterium tuberculosis.

Two lipoglycans, lipomannan (LM) and lipoarabinomannan (LAM), play various, albeit incompletely defined, roles in the interactions of mycobacteria with the host. Growing evidence points to the modification of LM and LAM with discrete covalent substituents as a strategy used by these bacteria to modulate their biological activities. One such substituent, originally identified in Mycobacterium tuberculosis (Mtb), is a 5-methylthio-d-xylose (MTX) sugar, which accounts for the antioxidative properties of LAM. The widespread distribution of this motif across Mtb isolates from several epidemiologically important lineages have stimulated interest in MTX-modified LAM as a biomarker of tuberculosis infection. Yet, several lines of evidence indicate that MTX may not be restricted to Mtb and that this motif may substitute more acceptors than originally thought. Using a highly specific monoclonal antibody to the MTX capping motif of Mtb LAM, we here show that MTX motifs not only substitute the mannoside caps of LAM but also the mannan core of LM in Mtb. MTX substituents were also found on the LM and LAM of pathogenic, slow-growing nontuberculous mycobacteria. The presence of MTX substituents on the LM and LAM from Mtb enhances the pro-apoptotic properties of both lipoglycans on LPS-stimulated THP-1 macrophages. A comparison of the cytokines and chemokines produced by resting and LPS-activated THP-1 cells upon exposure to MTX-proficient versus MTX-deficient LM further indicates that MTX substituents confer anti-inflammatory properties upon LM. These findings add to our understanding of the glycan-based strategies employed by slow-growing pathogenic mycobacteria to alter the host immune response to infection.

Role of succinyl substituents in the mannose-capping of lipoarabinomannan and control of inflammation in Mycobacterium tuberculosis infection.

The covalent modification of bacterial (lipo)polysaccharides with discrete substituents may impact their biosynthesis, export and/or biological activity. Whether mycobacteria use a similar strategy to control the biogenesis of its cell envelope polysaccharides and modulate their interaction with the host during infection is unknown despite the report of a number of tailoring substituents modifying the structure of these glycans. Here, we show that discrete succinyl substituents strategically positioned on Mycobacterium tuberculosis (Mtb) lipoarabinomannan govern the mannose-capping of this lipoglycan and, thus, much of the biological activity of the entire molecule. We further show that the absence of succinyl substituents on the two main cell envelope glycans of Mtb, arabinogalactan and lipoarabinomannan, leads to a significant increase of pro-inflammatory cytokines and chemokines in infected murine and human macrophages. Collectively, our results validate polysaccharide succinylation as a critical mechanism by which Mtb controls inflammation.

Evaluation of Toxicity Equivalency Factors of Tetrodotoxin Analogues with a Neuro-2a Cell-Based Assay and Application to Puffer Fish from Greece.

Tetrodotoxin (TTX) is a potent marine neurotoxin involved in poisoning cases, especially through the consumption of puffer fish. Knowledge of the toxicity equivalency factors (TEFs) of TTX analogues is crucial in monitoring programs to estimate the toxicity of samples analyzed with instrumental analysis methods. In this work, TTX analogues were isolated from the liver of a Lagocephalus sceleratus individual caught on South Crete coasts. A cell-based assay (CBA) for TTXs was optimized and applied to the establishment of the TEFs of 5,11-dideoxyTTX, 11-norTTX-6(S)-ol, 11-deoxyTTX and 5,6,11-trideoxyTTX. Results showed that all TTX analogues were less toxic than the parent TTX, their TEFs being in the range of 0.75-0.011. Then, different tissues of three Lagocephalus sceleratus individuals were analyzed with CBA and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The obtained TEFs were applied to the TTX analogues' concentrations obtained by LC-MS/MS analysis, providing an indication of the overall toxicity of the sample. Information about the TEFs of TTX analogues is valuable for food safety control, allowing the estimation of the risk of fish products to consumers.

Ciguatoxin-like toxicity distribution in flesh of amberjack (Seriola spp.) and dusky grouper (Epinephelus marginatus).

Ciguatoxins (CTXs) are marine neurotoxins that cause ciguatera poisoning (CP), mainly through the consumption of fish. The distribution of CTXs in fish is known to be unequal. Studies have shown that viscera accumulate more toxins than muscle, but little has been conducted on toxicity distribution in the flesh, which is the main edible part of fish, and the caudal muscle is also most commonly targeted for the monitoring of CTXs in the Canary Islands. At present, whether this sample is representative of the toxicity of an individual is undisclosed. This study aims to assess the distribution of CTXs in fish, considering different muscle samples, the liver, and gonads. To this end, tissues from four amberjacks (Seriola spp.) and four dusky groupers (Epinephelus marginatus), over 16.5 kg and captured in the Canary Islands, were analyzed by neuroblastoma-2a cell-based assay. Flesh samples were collected from the extraocular region (EM), head (HM), and different areas from the fillet (A-D). In the amberjack, the EM was the most toxic muscle (1.510 CTX1B Eq·g-1), followed by far for the caudal section of the fillet (D) (0.906 CTX1B Eq·g-1). In the dusky grouper flesh samples, D and EM showed the highest toxicity (0.279 and 0.273 CTX1B Eq·g-1). In both species, HM was one of the least toxic samples (0.421 and 0.166 CTX1B Eq·g-1). The liver stood out for its high CTX concentration (3.643 and 2.718 CTX1B Eq·g-1), as were the gonads (1.620 and 0.992 CTX1B Eq·g-1). According to these results, the caudal muscle next to the tail is a reliable part for use in determining the toxicity of fish flesh to guarantee its safe consumption. Additionally, the analysis of the liver and gonads could provide further information on doubtful specimens, and be used for CTX monitoring in areas with an unknown prevalence of ciguatera.

A Far-Red Molecular Rotor Fluorogenic Trehalose Probe for Live Mycobacteria Detection and Drug-Susceptibility Testing.

Increasing the speed, specificity, sensitivity, and accessibility of mycobacteria detection tools are important challenges for tuberculosis (TB) research and diagnosis. In this regard, previously reported fluorogenic trehalose analogues have shown potential, but their green-emitting dyes may limit sensitivity and applications in complex settings. Here, we describe a trehalose-based fluorogenic probe featuring a molecular rotor turn-on fluorophore with bright far-red emission (RMR-Tre). RMR-Tre, which exploits the unique biosynthetic enzymes and environment of the mycobacterial outer membrane to achieve fluorescence activation, enables fast, no-wash, low-background fluorescence detection of live mycobacteria. Aided by the red-shifted molecular rotor fluorophore, RMR-Tre exhibited up to a 100-fold enhancement in M. tuberculosis labeling compared to existing fluorogenic trehalose probes. We show that RMR-Tre reports on M. tuberculosis drug resistance in a facile assay, demonstrating its potential as a TB diagnostic tool.

Metabolic Hepatic Disorders Caused by Ciguatoxins in Goldfish (Carassius auratus).

Ciguatera poisoning (CP) is a foodborne disease known for centuries; however, little research has been conducted on the effects of ciguatoxins (CTXs) on fish metabolism. The main objective of this study was to assess different hepatic compounds observed in goldfish (Carassius auratus) fed C-CTX1 using nuclear magnetic resonance (NMR)-based metabolomics. Thirteen goldfish were treated with C-CTX1-enriched flesh and sampled on days 1, 8, 15, 29, 36, and 43. On day 43, two individuals, referred to as 'Detox', were isolated until days 102 and 121 to evaluate the possible recovery after returning to a commercial feed. At each sampling, hepatic tissue was weighed to calculate the hepatosomatic index (HSI) and analyzed for the metabolomics study; animals fed toxic flesh showed a higher HSI, even greater in the 'Detox' individuals. Furthermore, altered concentrations of alanine, lactate, taurine, glucose, and glycogen were observed in animals with the toxic diet. These disturbances could be related to an increase in ammonium ion (NH4+) production. An increase in ammonia (NH3) concentration in water was observed in the aquarium where the fish ingested toxic meat compared to the non-toxic aquarium. All these changes may be rationalized by the relationship between CTXs and the glucose-alanine cycle.

Mucosal exposure to non-tuberculous mycobacteria elicits B cell-mediated immunity against pulmonary tuberculosis.

Bacille Calmette-Guerin (BCG) is the only licensed vaccine against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) disease. However, BCG has limited efficacy, necessitating the development of better vaccines. Non-tuberculous mycobacteria (NTMs) are opportunistic pathogens present ubiquitously in the environment. TB endemic countries experience higher exposure to NTMs, but previous studies have not elucidated the relationship between NTM exposure and BCG efficacy against TB. Therefore, we develop a mouse model (BCG + NTM) to simulate human BCG immunization regime and continuous NTM exposure. BCG + NTM mice exhibit superior and prolonged protection against pulmonary TB, with increased B cell influx and anti-Mtb antibodies in serum and airways, compared with BCG alone. Notably, spatial transcriptomics and immunohistochemistry reveal that BCG + NTM mice formed B cell aggregates with features of germinal center development, which correlate with reduced Mtb burden. Our studies suggest a direct relationship between NTM exposure and TB protection, with B cells playing a crucial role.

Kinetics of the invasion of a non-phagocytic fish cell line, RTG-2 by Yersinia ruckeri serotype O1 biotype 1.

Yersiniosis, caused by the fish pathogen Yersinia ruckeri, is a serious bacterial septicaemia affecting mainly salmonids worldwide. The acute infection may result in high mortality without apparent external disease signs, while the chronic one causes moderate to considerable mortality. Survivors of yersiniosis outbreaks become carriers. Y. ruckeri is able to adhere to, and to invade, phagocytic and non-phagocytic fish cells by using unknown molecular mechanisms. The aim of this study was to describe the kinetics of cell invasion by Y. ruckeri serotype O1 biotype 1 in a fish cell line (RTG-2) originating from rainbow trout gonads. The efficiency of invasion by Y. ruckeri was found to be temperature dependent, having a maximum at 20 °C. The bacterium was able to survive up to 96 h postinfection. The incubation of the cells at 4 °C and the pre-incubation of the bacteria with sugars or heat-inactivated antiserum significantly decreased the efficiency of invasion or even completely prevented the invasion of RTG-2 cells. These findings indicate that Y. ruckeri is capable of adhering to, entering and surviving within non-phagocytic cells, and that the intracellular environment may constitute a suitable niche for this pathogen that can favour the spread of infection and/or the maintenance of a carrier state of fish.

Ciguatoxin Detection in Flesh and Liver of Relevant Fish Species from the Canary Islands.

The Canary Islands are a ciguatoxin (CTX) hotspot with an established official monitoring for the detection of CTX in fish flesh from the authorised points of first sale. Fish caught by recreational fishermen are not officially tested and the consumption of toxic viscera or flesh could lead to ciguatera poisoning (CP). The objectives of this study were to determine the presence of CTX-like toxicity in relevant species from this archipelago, compare CTX levels in liver and flesh and examine possible factors involved in their toxicity. Sixty amberjack (Seriola spp.), 27 dusky grouper (Epinephelus marginatus), 11 black moray eels (Muraena helena) and 11 common two-banded seabream (Diplodus vulgaris) were analysed by cell-based assay (CBA) and Caribbean ciguatoxin-1 (C-CTX1) was detected by liquid chromatography mass spectrometry (LC-MS/MS) in all these species. Most of the liver displayed higher CTX levels than flesh and even individuals without detectable CTX in flesh exhibited hepatic toxicity. Black moray eels stand out for the large difference between CTX concentration in both tissues. None of the specimens with non-toxic liver showed toxicity in flesh. This is the first evidence of the presence of C-CTX1 in the common two-banded seabream and the first report of toxicity comparison between liver and muscle from relevant fish species captured in the Canary Islands.

On the Different Faces of the Supercritical Phase of Water at a Near-Critical Temperature: Pressure-Induced Structural Transitions Ranging from a Gaslike Fluid to a Plastic Crystal Polymorph.

The present study reports a systematic analysis of a wide variety of structural, thermodynamic, and dynamic properties of supercritical water along the near-critical isotherm of T = 1.03Tc and up to extreme pressures, using molecular dynamics and Monte Carlo simulations. The methodology employed provides solid evidence about the existence of a structural transition from a liquidlike fluid to a compressed, tightly packed liquid, in the density and pressure region around 3.4ρc and 1.17 GPa, introducing an alternative approach to locate the crossing of the Frenkel line. Around 8.5 GPa another transition to a face-centered-cubic plastic crystal polymorph with density 5.178ρc is also observed, further confirmed by Gibbs free energy calculations using the two-phase thermodynamic model. The isobaric heat capacity maximum, closely related to the crossing of the Widom line, has also been observed around 0.8ρc, where the local density augmentation is also maximized. Another structural transition has been observed at 0.2ρc, related to the transformation of the fluid to a dilute gas at lower densities. These findings indicate that a near-critical isotherm can be divided into different domains where supercritical water exhibits distinct behavior, ranging from a gaslike one to a plastic crystal one.

One Metre Plus (1M+): A Multifunctional Open-Source Sensor for Bicycles Based on Raspberry Pi.

During the last decade, bicycles equipped with sensors became an essential tool for research, particularly for studies analyzing the lateral passing distance between motorized vehicles and bicycles. The objective of this article is to describe a low-cost open-source sensor called one metre plus (1m+) capable of measuring lateral passing distance, registering the geographical position of the cyclist, and video-recording the trip. The plans, codes, and schematic design are open and therefore easily accessible for the scientific community. This study describes in detail the conceptualization process, the characteristics of the device, and the materials from which they are made. The study also provides an evaluation of the product and describes the sensor's functionalities and its field of application. The objective of this project is to democratize research and develop a platform/participative project that offers tools to researchers worldwide, in order to standardize knowledge sharing and facilitate the comparability of results in various contexts.

Screening of New Potential Probiotics Strains against Photobacterium damselae Subsp. piscicida for Marine Aquaculture.

On intensive fish farms, 10% of the population dies exclusively from pathogens, and Photobacterium damselae subsp. Piscicida (Ph. damselae subsp. Piscicida), the bacteria causing pasteurellosis in marine aquaculture, is one of the major pathogens involved. The objective of this study was to obtain new probiotic strains against pasteurellosis in order to limit the use of chemotherapy, avoiding the environmental repercussions generated by the abusive use of these products. In this study, 122 strains were isolated from the gills and intestines of different marine fish species and were later evaluated in vitro to demonstrate the production of antagonistic effects, the production of antibacterial substances, adhesion and growth to mucus, resistance to bile and resistance to pH gradients, as well as its harmlessness and the dynamic of expression of immune-related genes by real-time PCR after administration of the potential probiotic in the fish diet. Only 1/122 strains showed excellent results to be considered as a potential probiotic strain and continue its characterization against Ph. damselae subsp. piscicida to determine its protective effect and elucidating in future studies its use as a possible probiotic strain for marine aquaculture.

Antigen Presentation of mRNA-Based and Virus-Vectored SARS-CoV-2 Vaccines.

Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which has reached pandemic proportions. A number of effective vaccines have been produced, including mRNA vaccines and viral vector vaccines, which are now being implemented on a large scale in order to control the pandemic. The mRNA vaccines are composed of viral Spike S1 protein encoding mRNA incorporated in a lipid nanoparticle and stabilized by polyethylene glycol (PEG). The mRNA vaccines are novel in many respects, including cellular uptake and the intracellular routing, processing, and secretion of the viral protein. Viral vector vaccines have incorporated DNA sequences, encoding the SARS-CoV-2 Spike protein into (attenuated) adenoviruses. The antigen presentation routes in MHC class I and class II, in relation to the induction of virus-neutralizing antibodies and cytotoxic T-lymphocytes, will be reviewed. In rare cases, mRNA vaccines induce unwanted immune mediated side effects. The mRNA-based vaccines may lead to an anaphylactic reaction. This reaction may be triggered by PEG. The intracellular routing of PEG and potential presentation in the context of CD1 will be discussed. Adenovirus vector-based vaccines have been associated with thrombocytopenic thrombosis events. The anti-platelet factor 4 antibodies found in these patients could be generated due to conformational changes of relevant epitopes presented to the immune system.

A Whole Virion Vaccine for COVID-19 Produced via a Novel Inactivation Method and Preliminary Demonstration of Efficacy in an Animal Challenge Model.

The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation. We report on the use of a novel method (SolaVAX) for production of an inactivated vaccine candidate and the testing of that candidate in a hamster animal model for its ability to prevent infection upon challenge with SARS-CoV-2 virus. The studies employed in this work included an evaluation of the levels of neutralizing antibody produced post-vaccination, levels of specific antibody sub-types to RBD and spike protein that were generated, evaluation of viral shedding post-challenge, flow cytometric and single cell sequencing data on cellular fractions and histopathological evaluation of tissues post-challenge. The results from this preliminary evaluation provide insight into the immunological responses occurring as a result of vaccination with the proposed vaccine candidate and the impact that adjuvant formulations, specifically developed to promote Th1 type immune responses, have on vaccine efficacy and protection against infection following challenge with live SARS-CoV-2. This data may have utility in the development of effective vaccine candidates broadly. Furthermore, the results of this preliminary evaluation suggest that preparation of a whole virion vaccine for COVID-19 using this specific photochemical method may have potential utility in the preparation of one such vaccine candidate.

Structure and dynamics of water plastic crystals from computer simulations.

Water has a rich phase diagram with several crystals, as confirmed by experiments. High-pressure and high-temperature water is of interest for Earth's mantle and exoplanetary investigations. It is in this region of the phase diagram of water that new plastic crystal phases of water have been revealed via computer simulations by both classical forcefields and ab initio calculations. However, these plastic phases still remain elusive in experiments. Here, we present a complete characterization of the structure, dynamics, and thermodynamics of the computational plastic crystal phases of water using molecular dynamics and the two-phase thermodynamic method and uncover the interplay between them. The relaxation times of different reorientational correlation functions are obtained for the hypothetical body-centered-cubic and face-centered-cubic plastic crystal phases of water at T = 440 K and P = 8 GPa. Results are compared to a high pressure liquid and ice VII phases to improve the understanding of the plastic crystal phases. Entropy results indicate that the fcc crystal is more stable compared to the bcc structure under the studied conditions.