bluuebunny/crossref_metadata_2025 huggingface dataset:
The Reactivity of Human and Equine Estrogen Quinones towards Purine Nucleosides
Authors: Benedek Zsolt , Girnt Peter , Olah Julianna
Published: September 2021

Conjugated estrogen medicines, which are produced from the urine of pregnant mares for the purpose of menopausal hormone replacement therapy (HRT), contain the sulfate conjugates of estrone, equilin, and equilenin in varying proportions. The latter three steroid sex hormones are highly similar in molecular structure as they only differ in the degree of unsaturation of the sterane ring “B”: the cyclohexene ring in estrone (which is naturally present in both humans and horses) is replaced by more symmetrical cyclohexadiene and benzene rings in the horse-specific (“equine”) hormones equilin and equilenin, respectively. Though the structure of ring “B” has only moderate influence on the estrogenic activity desired in HRT, it might still significantly affect the reactivity in potential carcinogenic pathways. In the present theoretical study, we focus on the interaction of estrogen orthoquinones, formed upon metabolic oxidation of estrogens in breast cells with purine nucleosides. This multistep process results in a purine base loss in the DNA chain (depurination) and the formation of a “depurinating adduct” from the quinone and the base. The point mutations induced in this manner are suggested to manifest in breast cancer development in the long run. We examine six reactions between deoxyadenosine and deoxyguanosine as nucleosides and estrone-3,4-quinone, equilin-3,4-quinone, and equilenin-3,4-quinone as mutagens. We performed DFT calculations to determine the reaction mechanisms and establish a structure–reactivity relationship between the degree of unsaturation of ring “B” and the expected rate of DNA depurination. As quinones might be present in the cytosol in various protonated forms, we introduce the concept of “effective barriers” to account for the different reactivity and different concentrations of quinone derivatives. According to our results, both equine estrogens have the potential to facilitate depurination as the activation barrier of one of the elementary steps (the initial Michael addition in the case of equilenin and the rearomatization step in the case of equilin) significantly decreases compared to that of estrone. We conclude that the appearance of exogenous equine estrogen quinones due to HRT might increase the risk of depurination-induced breast cancer development compared to the exposure to endogenous estrone metabolites. Still, further studies are required to identify the rate-limiting step of depurination under intracellular conditions to reveal whether the decrease in the barriers affects the overall rate of carcinogenesis.
Implant Periapical Lesion: A Narrative Review
Authors: Chang Li-Ching
Published: September 2021

Implant periapical lesion (IPL) is an infectious-inflammatory alteration surrounding an implant apex. It is a multifactorial disease that may ultimately cause implant failure. The diagnosis of IPL is based on examination of clinical manifestations and apical radiolucency. Many etiologies have been attributed to IPL, including preexisting microbial pathology and surgical trauma. Moreover, many systems have been used to classify IPL based on different parameters. To date, non-surgical and surgical treatment, as well as removal of failed implants, have been considered to successfully manage IPL. However, prevention of IPL surpasses all modes of treatment. An increased number of IPL cases are expected as implants have become standard for tooth replacement in dentate arches. Therefore, it is necessary to understand IPL more comprehensively. Herein, an introduction to IPL, including its etiology, diagnosis, classification, treatment, and prevention, has been undertaken.
New Cytoplasmic Virus-Like Elements (VLEs) in the Yeast Debaryomyces hansenii
Authors: Połomska Xymena , Neuvéglise Cécile , Zyzak Joanna , Żarowska Barbara , Casaregola Serge , Lazar Zbigniew
Published: September 2021

Yeasts can have additional genetic information in the form of cytoplasmic linear dsDNA molecules called virus-like elements (VLEs). Some of them encode killer toxins. The aim of this work was to investigate the prevalence of such elements in D. hansenii killer yeast deposited in culture collections as well as in strains freshly isolated from blue cheeses. Possible benefits to the host from harboring such VLEs were analyzed. VLEs occurred frequently among fresh D. hansenii isolates (15/60 strains), as opposed to strains obtained from culture collections (0/75 strains). Eight new different systems were identified: four composed of two elements and four of three elements. Full sequences of three new VLE systems obtained by NGS revealed extremely high conservation among the largest molecules in these systems except for one ORF, probably encoding a protein resembling immunity determinant to killer toxins of VLE origin in other yeast species. ORFs that could be potentially involved in killer activity due to similarity to genes encoding proteins with domains of chitin-binding/digesting and deoxyribonuclease NucA/NucB activity, could be distinguished in smaller molecules. However, the discovered VLEs were not involved in the biocontrol of Yarrowia lipolytica and Penicillium roqueforti present in blue cheeses.
Venom Immunotherapy: From Proteins to Product to Patient Protection
Authors: Feindor Martin , Heath Matthew D. , Hewings Simon J. , Carreno Velazquez Thalia L. , Blank Simon , Grosch Johannes , Jakob Thilo , Schmid-Grendelmeier Peter , Klimek Ludger , Golden David B. K. , Skinner Murray A. , Kramer Matthias F.
Published: September 2021

In this review, we outline and reflect on the important differences between allergen-specific immunotherapy for inhalant allergies (i.e., aeroallergens) and venom-specific immunotherapy (VIT), with a special focus on Venomil® Bee and Wasp. Venomil® is provided as a freeze-dried extract and a diluent to prepare a solution for injection for the treatment of patients with IgE-mediated allergies to bee and/or wasp venom and for evaluating the degree of sensitivity in a skin test. While the materials that make up the product have not changed, the suppliers of raw materials have changed over the years. Here, we consolidate relevant historical safety and efficacy studies that used products from shared manufacture supply profiles, i.e., products from Bayer or Hollister–Stier. We also consider the characterization and standardization of venom marker allergens, providing insights into manufacturing controls that have produced stable and consistent quality profiles over many years. Quality differences between products and their impacts on treatment outcomes have been a current topic of discussion and further research. Finally, we review the considerations surrounding the choice of depot adjuvant most suitable to augmenting VIT.
Potential of Near Infrared Spectroscopy as a Rapid Method to Discriminate OTA and Non-OTA-Producing Mould Species in a Dry-Cured Ham Model System
Authors: Cebrián Eva , Núñez Félix , Rodríguez Mar , Grassi Silvia , González-Mohino Alberto
Published: September 2021

The ripening process of dry-cured meat products is characterised by the development of fungi on the product’s surface. This population plays a beneficial role, but, uncontrolled moulds represent a health risk, since some of them may produce mycotoxins, such as ochratoxin A (OTA). The aim of the present work is to assess the potential of near-infrared spectroscopy (NIRS) for the detection of OTA-producing mould species on dry-cured ham-based agar. The collected spectra were used to develop Support Vector Machines–Discriminant Analysis (SVM-DA) models by a hierarchical approach. Firstly, an SVM-DA model was tested to discriminate OTA and non-OTA producers; then, two models were tested to discriminate species among the OTA producers and the non-OTA producers. OTA and non-OTA-producing moulds were discriminated with 85% sensitivity and 86% specificity in the prediction. Furthermore, the SVM-DA model could differentiate non-OTA-producing species with a 95% sensitivity and specificity. Promising results were obtained for the prediction of the four OTA-producing species tested, with a 69% and 90% sensitivity and specificity, respectively. The preliminary approach demonstrated the high potential of NIR spectroscopy, coupled with Chemometrics, to be used as a real-time automated routine monitorization of dry-cured ham surfaces.
The History of Pertussis Toxin
Authors: Locht Camille , Antoine Rudy
Published: September 2021

Besides the typical whooping cough syndrome, infection with Bordetella pertussis or immunization with whole-cell vaccines can result in a wide variety of physiological manifestations, including leukocytosis, hyper-insulinemia, and histamine sensitization, as well as protection against disease. Initially believed to be associated with different molecular entities, decades of research have provided the demonstration that these activities are all due to a single molecule today referred to as pertussis toxin. The three-dimensional structure and molecular mechanisms of pertussis toxin action, as well as its role in protective immunity have been uncovered in the last 50 years. In this article, we review the history of pertussis toxin, including the paradigm shift that occurred in the 1980s which established the pertussis toxin as a single molecule. We describe the role molecular biology played in the understanding of pertussis toxin action, its role as a molecular tool in cell biology and as a protective antigen in acellular pertussis vaccines and possibly new-generation vaccines, as well as potential therapeutical applications.
Doxycycline Inhibition of a Pseudotyped Virus Transduction Does Not Translate to Inhibition of SARS-CoV-2 Infectivity
Authors: Diomede Luisa , Baroni Sara , De Luigi Ada , Piotti Arianna , Lucchetti Jacopo , Fracasso Claudia , Russo Luca , Bonaldo Valerio , Panini Nicolò , Filippini Federica , Fiordaliso Fabio , Corbelli Alessandro , Beeg Marten , Pizzato Massimo , Caccuri Francesca , Gobbi Marco , Biasini Emiliano , Caruso Arnaldo , Salmona Mario
Published: September 2021

The rapid spread of the pandemic caused by the SARS-CoV-2 virus has created an unusual situation, with rapid searches for compounds to interfere with the biological processes exploited by the virus. Doxycycline, with its pleiotropic effects, including anti-viral activity, has been proposed as a therapeutic candidate for COVID-19 and about twenty clinical trials have started since the beginning of the pandemic. To gain information on the activity of doxycycline against SARS-CoV-2 infection and clarify some of the conflicting clinical data published, we designed in vitro binding tests and infection studies with a pseudotyped virus expressing the spike protein, as well as a clinically isolated SARS-CoV-2 strain. Doxycycline inhibited the transduction of the pseudotyped virus in Vero E6 and HEK-293 T cells stably expressing human receptor angiotensin-converting enzyme 2 but did not affect the entry and replication of SARS-CoV-2. Although this conclusion is apparently disappointing, it is paradigmatic of an experimental approach aimed at developing an integrated multidisciplinary platform which can shed light on the mechanisms of action of potential anti-COVID-19 compounds. To avoid wasting precious time and resources, we believe very stringent experimental criteria are needed in the preclinical phase, including infectivity studies with clinically isolated SARS-CoV-2, before moving on to (futile) clinical trials.
Genotype of Immunologically Hot or Cold Tumors Determines the Antitumor Immune Response and Efficacy by Fully Virulent Retargeted oHSV
Authors: Gianni Tatiana , Leoni Valerio , Sanapo Mara , Parenti Federico , Bressanin Daniela , Barboni Catia , Zaghini Anna , Campadelli-Fiume Gabriella , Vannini Andrea
Published: September 2021

We report on the efficacy of the non-attenuated HER2-retargeted oHSV named R-337 against the immunologically hot CT26-HER2 tumor, and an insight into the basis of the immune protection. Preliminarily, we conducted an RNA immune profiling and immune cell content characterization of CT26-HER2 tumor in comparison to the immunologically cold LLC1-HER2 tumor. CT26-HER2 tumor was implanted into HER2-transgenic BALB/c mice. Hallmarks of R-337 effects were the protection from primary tumor, long-term adaptive vaccination directed to both HER2 and CT26-wt cell neoantigens. The latter effect differentiated R-337 from OncoVEXGM-CSF. As to the basis of the immune protection, R-337 orchestrated several changes to the tumor immune profile, which cumulatively reversed the immunosuppression typical of this tumor (graphical abstract). Thus, Ido1 (inhibitor of T cell anticancer immunity) levels and T regulatory cell infiltration were decreased; Cd40 and Cd27 co-immunostimulatory markers were increased; the IFNγ cascade was activated. Of note was the dampening of IFN-I response, which we attribute to the fact that R-337 is fully equipped with genes that contrast the host innate response. The IFN-I shut-down likely favored viral replication and the expression of the mIL-12 payload, which, in turn, boosted the antitumor response. The results call for a characterization of tumor immune markers to employ oncolytic herpesviruses more precisely.
Therapeutic Potential of IL-15 and N-803 in HIV/SIV Infection
Authors: Harwood Olivia , O’Connor Shelby
Published: September 2021

IL-15, a proinflammatory cytokine critical for the generation, maintenance, and homeostasis of T cell responses, is produced naturally in response to HIV/SIV infection, but has also demonstrated therapeutic potential. IL-15 can boost CD4+ and CD8+ T cell and NK cell proliferation, activation, and function. However, IL-15 treatment may cause aberrant immune activation and accelerated disease progression in certain circumstances. Moreover, the relationship between the timing of IL-15 administration and disease progression remains unclear. The IL-15 superagonist N-803 was developed to expand the therapeutic potential of IL-15 by maximizing its tissue distribution and half-life. N-803 has garnered enthusiasm recently as a way to enhance the innate and cellular immune responses to HIV/SIV by improving CD8+ T cell recognition and killing of virus-infected cells and directing immune cells to mucosal sites and lymph nodes, the primary sites of virus replication. N-803 has also been evaluated in “shock and kill” strategies due to its potential to reverse latency (shock) and enhance antiviral immunity (kill). This review examines the current literature about the effects of IL-15 and N-803 on innate and cellular immunity, viral burden, and latency reversal in the context of HIV/SIV, and their therapeutic potential both alone and combined with additional interventions such as antiretroviral therapy (ART) and vaccination.
Clinical Evaluation of In-House-Produced 3D-Printed Nasopharyngeal Swabs for COVID-19 Testing
Authors: Grandjean Lapierre Simon , Bedwani Stéphane , DeBlois François , Fortin Audray , Zamorano Cuervo Natalia , Zerouali Karim , Caron Elise , Morency-Potvin Philippe , Gagnon Simon , Nguissan Nakome , Arlotto Pascale , Hardy Isabelle , Boutin Catherine-Audrey , Tremblay Cécile , Coutlée François , de Guise Jacques , Grandvaux Nathalie
Published: September 2021

3D-printed alternatives to standard flocked swabs were rapidly developed to provide a response to the unprecedented and sudden need for an exponentially growing amount of diagnostic tools to fight the COVID-19 pandemic. In light of the anticipated shortage, a hospital-based 3D-printing platform was implemented in our institution for the production of swabs for nasopharyngeal and oropharyngeal sampling based on the freely available, open-source design provided to the community by University of South Florida’s Health Radiology and Northwell Health System teams as a replacement for locally used commercial swabs. Validation of our 3D-printed swabs was performed with a head-to-head diagnostic accuracy study of the 3D-printed “Northwell model” with the cobas PCR Media® swab sample kit. We observed an excellent concordance (total agreement 96.8%, Kappa 0.936) in results obtained with the 3D-printed and flocked swabs, indicating that the in-house 3D-printed swab could be used reliably in the context of a shortage of flocked swabs. To our knowledge, this is the first study to report on autonomous hospital-based production and clinical validation of 3D-printed swabs.
Work-Related Human T-lymphotropic Virus 1 and 2 (HTLV-1/2) Infection: A Systematic Review
Authors: Stufano Angela , Jahantigh Hamid Reza , Cagnazzo Francesco , Centrone Francesca , Loconsole Daniela , Chironna Maria , Lovreglio Piero
Published: September 2021

Human T-lymphotropic virus 1 and 2 (HTLV-1/2) belong to the delta group of retroviruses which may cause a life-long infection in humans, HTLV-1 leading to adult T-cell leukemia/lymphoma and other diseases. Different transmission modes have been described, such as breastfeeding, and, as for other blood-borne pathogens, unsafe sexual activity, intravenous drug usage, and blood transfusion and transplantation. The present systematic review was conducted to identify all peer-reviewed studies concerning the work-related infection by HTLV-1/2. A literature search was conducted from January to May 2021, according to the PRISMA methodology, selecting 29 studies: seven related to health care workers (HCWs), five to non-HCWs, and 17 to sex workers (SWs). The findings showed no clear evidence as to the possibility of HTLV-1/2 occupational transmission in HCWs, according to the limited number and quality of the papers. Moreover, non-HCWs showed a higher prevalence in jobs consistent with a lower socioeconomic status or that could represent a familial cluster, and an increased risk of zoonotic transmission from STLV-1-infected non-human primates has been observed in African hunters. Finally, a general increase of HTLV-1 infection was observed in SWs, whereas only one paper described an increased prevalence for HTLV-2, supporting the urgent need for prevention and control measures, including screening, diagnosis, and treatment of HTLV-1/2, to be offered routinely as part of a comprehensive approach to decrease the impact of sexually transmitted diseases in SWs.
Drivers and Distribution of Henipavirus-Induced Syncytia: What Do We Know?
Authors: Gamble Amandine , Yeo Yao Yu , Butler Aubrey A. , Tang Hubert , Snedden Celine E. , Mason Christian T. , Buchholz David W. , Bingham John , Aguilar Hector C. , Lloyd-Smith James O.
Published: September 2021

Syncytium formation, i.e., cell–cell fusion resulting in the formation of multinucleated cells, is a hallmark of infection by paramyxoviruses and other pathogenic viruses. This natural mechanism has historically been a diagnostic marker for paramyxovirus infection in vivo and is now widely used for the study of virus-induced membrane fusion in vitro. However, the role of syncytium formation in within-host dissemination and pathogenicity of viruses remains poorly understood. The diversity of henipaviruses and their wide host range and tissue tropism make them particularly appropriate models with which to characterize the drivers of syncytium formation and the implications for virus fitness and pathogenicity. Based on the henipavirus literature, we summarized current knowledge on the mechanisms driving syncytium formation, mostly acquired from in vitro studies, and on the in vivo distribution of syncytia. While these data suggest that syncytium formation widely occurs across henipaviruses, hosts, and tissues, we identified important data gaps that undermined our understanding of the role of syncytium formation in virus pathogenesis. Based on these observations, we propose solutions of varying complexity to fill these data gaps, from better practices in data archiving and publication for in vivo studies, to experimental approaches in vitro.
Report of One-Year Prospective Surveillance of SARS-CoV-2 in Dogs and Cats in France with Various Exposure Risks: Confirmation of a Low Prevalence of Shedding, Detection and Complete Sequencing of an Alpha Variant in a Cat
Authors: Krafft Emilie , Denolly Solène , Boson Bertrand , Angelloz-Pessey Sophie , Levaltier Sophie , Nesi Nicolas , Corbet Sandrine , Leterrier Bryce , Fritz Matthieu , Leroy Eric M. , Gouilh Meriadeg Ar , Cosset François-Loïc , Kodjo Angeli , Legros Vincent
Published: September 2021

Despite the probable zoonotic origin of SARS-CoV-2, only limited research efforts have been made to understand the role of companion animals in SARS-CoV-2 epidemiology. According to recent serological prevalence studies, human-to-companion animal transmission is quite frequent, which led us to consider that the risk of SARS-CoV-2 transmission from animal to human, albeit negligible in the present context, may have been underestimated. In this study, we provide the results of a prospective survey that was conducted to evaluate the SARS-CoV-2 isolation rate by qRT-PCR in dogs and cats with different exposure risks and clinical statuses. From April 2020 to April 2021, we analyzed 367 samples and investigated the presence of SARS-CoV-2 RNA using qRT-PCR. Only four animals tested positive, all of them being cats. Three cats were asymptomatic and one presented a coryza-like syndrome. We describe in detail the infection in two cats and the associated clinical characteristics. Importantly, we obtained SARS-CoV-2 genomes from one infected animal and characterized them as Alpha variants. This represents the first identification of the SARS-CoV-2 Alpha variant in an infected animal in France.
Susceptibility of Goldfish to Cyprinid Herpesvirus 2 (CyHV-2) SH01 Isolated from Cultured Crucian Carp
Authors: Wen Jinxuan , Xu Yao , Su Meizhen , Lu Liqun , Wang Hao
Published: September 2021

Cyprinid herpesvirus 2 (CyHV-2), a member of the Alloherpesviridae family belonging to the genus Cyprinivirus, is a fatal contagious aquatic pathogen that affects goldfish (Carassius auratus) and crucian carp (Carassius carassius). Although crucian carp and goldfish belong to the genus Carassius, it is unclear whether they are susceptible to the same CyHV-2 isolate. In addition, the origin of the crucian carp-derived CyHV-2 virus isolate remains unclear. CyHV-2 SH01 was isolated during herpesviral hematopoietic necrosis disease (HVHN) outbreaks in crucian carp at a local fish farm near Shanghai. CyHV-2 SH01 was confirmed by PCR and Western blot analysis of kidney, spleen, muscle, and blood tissue from the diseased crucian carp. Moreover, histopathological and ultra-pathological analyses revealed pathological changes characteristic of CyHV-2 SH01 infection in the tissues of the diseased crucian carp. In the present study, goldfish and crucian carp were challenged with CyHV-2 SH01 to elucidate viral virulence. We found that CyHV-2 SH01 could cause rapid and fatal disease progression in goldfish and crucian carp 24 h post-injection at 28 °C. Experimental infection of goldfish by injection indicated that the average virus titer in the kidney of the goldfish was 103.47 to 103.59 copies/mg. In addition, tissues exhibited the most prominent histopathological changes (cellular wrinkling and shrinkage, cytoplasmic vacuolation, fusion of the gill lamellae, and hepatic congestion) in CyHV-2 SH01-infected goldfish and crucian carp. Thus, crucian carp and goldfish showed a high sensitivity, with typical symptoms, to HVHN disease caused by CyHV-2 SH01.
Rasch Model of the COVID-19 Symptom Checklist—A Psychometric Validation Study
Authors: Stamm Tanja A. , Ritschl Valentin , Omara Maisa , Andrews Margaret R. , Mevenkamp Nils , Rzepka Angelika , Schirmer Michael , Walch Siegfried , Salzberger Thomas , Mosor Erika
Published: September 2021

While self-reported Coronavirus Disease 2019 (COVID-19) symptom checklists have been extensively used during the pandemic, they have not been sufficiently validated from a psychometric perspective. We, therefore, used advanced psychometric modelling to explore the construct validity and internal consistency of an online self-reported COVID-19 symptom checklist and suggested adaptations where necessary. Fit to the Rasch model was examined in a sample of 1638 Austrian citizens who completed the checklist on up to 20 days during a lockdown. The items’ fatigue’, ‘headache’ and ‘sneezing’ had the highest likelihood to be affirmed. The longitudinal application of the symptom checklist increased the fit to the Rasch model. The item ‘cough’ showed a significant misfit to the fundamental measurement model and an additional dependency to ‘dry cough/no sputum production’. Several personal factors, such as gender, age group, educational status, COVID-19 test status, comorbidities, immunosuppressive medication, pregnancy and pollen allergy led to systematic differences in the patterns of how symptoms were affirmed. Raw scores’ adjustments ranged from ±0.01 to ±0.25 on the metric scales (0 to 10). Except for some basic adaptations that increases the scale’s construct validity and internal consistency, the present analysis supports the combination of items. More accurate item wordings co-created with laypersons would lead to a common understanding of what is meant by a specific symptom. Adjustments for personal factors and comorbidities would allow for better clinical interpretations of self-reported symptom data.
CP100356 Hydrochloride, a P-Glycoprotein Inhibitor, Inhibits Lassa Virus Entry: Implication of a Candidate Pan-Mammarenavirus Entry Inhibitor
Authors: Takenaga Toru , Zhang Zihan , Muramoto Yukiko , Fehling Sarah Katharina , Hirabayashi Ai , Takamatsu Yuki , Kajikawa Junichi , Miyamoto Sho , Nakano Masahiro , Urata Shuzo , Groseth Allison , Strecker Thomas , Noda Takeshi
Published: September 2021

Lassa virus (LASV)—a member of the family Arenaviridae—causes Lassa fever in humans and is endemic in West Africa. Currently, no approved drugs are available. We screened 2480 small compounds for their potential antiviral activity using pseudotyped vesicular stomatitis virus harboring the LASV glycoprotein (VSV-LASVGP) and a related prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV). Follow-up studies confirmed that CP100356 hydrochloride (CP100356), a specific P-glycoprotein (P-gp) inhibitor, suppressed VSV-LASVGP, LCMV, and LASV infection with half maximal inhibitory concentrations of 0.52, 0.54, and 0.062 μM, respectively, without significant cytotoxicity. Although CP100356 did not block receptor binding at the cell surface, it inhibited low-pH-dependent membrane fusion mediated by arenavirus glycoproteins. P-gp downregulation did not cause a significant reduction in either VSV-LASVGP or LCMV infection, suggesting that P-gp itself is unlikely to be involved in arenavirus entry. Finally, our data also indicate that CP100356 inhibits the infection by other mammarenaviruses. Thus, our findings suggest that CP100356 can be considered as an effective virus entry inhibitor for LASV and other highly pathogenic mammarenaviruses.
The Input of Structural Vaccinology in the Search for Vaccines against Bunyaviruses
Authors: Serris Alexandra
Published: September 2021

A significant increase in the number of viruses causing unexpected illnesses and epidemics among humans, wildlife and livestock has been observed in recent years. These new or re-emerging viruses have often caught the scientific community off-guard, without sufficient knowledge to combat them, as shown by the current coronavirus pandemic. The bunyaviruses, together with the flaviviruses and filoviruses, are the major etiological agents of viral hemorrhagic fever, and several of them have been listed as priority pathogens by the World Health Organization for which insufficient countermeasures exist. Based on new techniques allowing rapid analysis of the repertoire of protective antibodies induced during infection, combined with atomic-level structural information on viral surface proteins, structural vaccinology is now instrumental in the combat against newly emerging threats, as it allows rapid rational design of novel vaccine antigens. Here, we discuss the contribution of structural vaccinology and the current challenges that remain in the search for an efficient vaccine against some of the deadliest bunyaviruses.
Nafamostat–Interferon-α Combination Suppresses SARS-CoV-2 Infection In Vitro and In Vivo by Cooperatively Targeting Host TMPRSS2
Authors: Ianevski Aleksandr , Yao Rouan , Lysvand Hilde , Grødeland Gunnveig , Legrand Nicolas , Oksenych Valentyn , Zusinaite Eva , Tenson Tanel , Bjørås Magnar , Kainov Denis E.
Published: September 2021

SARS-CoV-2 and its vaccine/immune-escaping variants continue to pose a serious threat to public health due to a paucity of effective, rapidly deployable, and widely available treatments. Here, we address these challenges by combining Pegasys (IFNα) and nafamostat to effectively suppress SARS-CoV-2 infection in cell culture and hamsters. Our results indicate that Serpin E1 is an important mediator of the antiviral activity of IFNα and that both Serpin E1 and nafamostat can target the same cellular factor TMPRSS2, which plays a critical role in viral replication. The low doses of the drugs in combination may have several clinical advantages, including fewer adverse events and improved patient outcome. Thus, our study may provide a proactive solution for the ongoing pandemic and potential future coronavirus outbreaks, which is still urgently required in many parts of the world.
Renewed Public Health Threat from Emerging Lyssaviruses
Authors: Fooks Anthony R. , Shipley Rebecca , Markotter Wanda , Tordo Noël , Freuling Conrad M. , Müller Thomas , McElhinney Lorraine M. , Banyard Ashley C. , Rupprecht Charles E.
Published: September 2021

Pathogen discovery contributes to our knowledge of bat-borne viruses and is linked to the heightened interest globally in bats as recognised reservoirs of zoonotic agents. The transmission of lyssaviruses from bats-to-humans, domestic animals, or other wildlife species is uncommon, but interest in these pathogens remains due to their ability to cause an acute, progressive, invariably fatal encephalitis in humans. Consequently, the detection and characterisation of bat lyssaviruses continues to expand our knowledge of their phylogroup definition, viral diversity, host species association, geographical distribution, evolution, mechanisms for perpetuation, and the potential routes of transmission. Although the opportunity for lyssavirus cross-species transmission seems rare, adaptation in a new host and the possibility of onward transmission to humans requires continued investigation. Considering the limited efficacy of available rabies biologicals it is important to further our understanding of protective immunity to minimize the threat from these pathogens to public health. Hence, in addition to increased surveillance, the development of a niche pan-lyssavirus vaccine or therapeutic biologics for post-exposure prophylaxis for use against genetically divergent lyssaviruses should be an international priority as these emerging lyssaviruses remain a concern for global public health.
A Structural Update of Neutralizing Epitopes on the HIV Envelope, a Moving Target
Authors: Parker Miller Emma , Finkelstein Maxwell T. , Erdman Molly C. , Seth Paul C. , Fera Daniela
Published: September 2021

Antibodies that can neutralize diverse HIV-1 strains develop in ~10–20% of HIV-1 infected individuals, and their elicitation is a goal of vaccine design. Such antibodies can also serve as therapeutics for those who have already been infected with the virus. Structural characterizations of broadly reactive antibodies in complex with the HIV-1 spike indicate that there are a limited number of sites of vulnerability on the spike. Analysis of their structures can help reveal commonalities that would be useful in vaccine design and provide insights on combinations of antibodies that can be used to minimize the incidence of viral resistance mutations. In this review, we give an update on recent structures determined of the spike in complex with broadly neutralizing antibodies in the context of all epitopes on the HIV-1 spike identified to date.
Tick-Borne Encephalitis Virus (TBEV) Infection in Two Horses
Authors: Conze Theresa Maria , Bagó Zoltán , Revilla-Fernández Sandra , Schlegel Jürgen , Goehring Lutz S. , Matiasek Kaspar
Published: September 2021

A final diagnosis in a horse with clinical signs of encephalopathy can be challenging despite the use of extensive diagnostics. Clinical signs are often not pathognomonic and need to be interpreted in combination with (specific) laboratory results and epidemiological data of the geographical region of the origin of the case(s). Here we describe the diagnostic pathway of tick-borne encephalitis virus infection in two horses using established molecular diagnostic methods and a novel in situ hybridization technique to differentiate between regionally important/emerging diseases for central Europe: (i) hepatoencephalopathy, (ii) Borna disease virus, and (iii) West Nile virus infections.
Special Issue “Emerging Viruses in Aquaculture”
Authors: Weidmann Manfred , El-Matbouli Mansour , Zeng Weiwei , Bergmann Sven M.
Published: September 2021

According to the 2018 FAO report on aquaculture, there are 598 species of finfish, molluscs, crustaceans, and other organisms used in aquafarming around the world [...]
Evidence That the Adenovirus Single-Stranded DNA Binding Protein Mediates the Assembly of Biomolecular Condensates to Form Viral Replication Compartments
Authors: Hidalgo Paloma , Pimentel Arturo , Mojica-Santamaría Diana , von Stromberg Konstantin , Hofmann-Sieber Helga , Lona-Arrona Christian , Dobner Thomas , González Ramón A.
Published: September 2021

A common viral replication strategy is characterized by the assembly of intracellular compartments that concentrate factors needed for viral replication and simultaneously conceal the viral genome from host-defense mechanisms. Recently, various membrane-less virus-induced compartments and cellular organelles have been shown to represent biomolecular condensates (BMCs) that assemble through liquid-liquid phase separation (LLPS). In the present work, we analyze biophysical properties of intranuclear replication compartments (RCs) induced during human adenovirus (HAdV) infection. The viral ssDNA-binding protein (DBP) is a major component of RCs that contains intrinsically disordered and low complexity proline-rich regions, features shared with proteins that drive phase transitions. Using fluorescence recovery after photobleaching (FRAP) and time-lapse studies in living HAdV-infected cells, we show that DBP-positive RCs display properties of liquid BMCs, which can fuse and divide, and eventually form an intranuclear mesh with less fluid-like features. Moreover, the transient expression of DBP recapitulates the assembly and liquid-like properties of RCs in HAdV-infected cells. These results are of relevance as they indicate that DBP may be a scaffold protein for the assembly of HAdV-RCs and should contribute to future studies on the role of BMCs in virus-host cell interactions.
Universally Immune: How Infection Permissive Next Generation Influenza Vaccines May Affect Population Immunity and Viral Spread
Authors: Bull Maireid B. , Cohen Carolyn A. , Leung Nancy H.L. , Valkenburg Sophie A.
Published: September 2021

Next generation influenza vaccines that target conserved epitopes are becoming a clinical reality but still have challenges to overcome. Universal next generation vaccines are considered a vital tool to combat future pandemic viruses and have the potential to vastly improve long-term protection against seasonal influenza viruses. Key vaccine strategies include HA-stem and T cell activating vaccines; however, they could have unintended effects for virus adaptation as they recognise the virus after cell entry and do not directly block infection. This may lead to immune pressure on residual viruses. The potential for immune escape is already evident, for both the HA stem and T cell epitopes, and mosaic approaches for pre-emptive immune priming may be needed to circumvent key variants. Live attenuated influenza vaccines have not been immunogenic enough to boost T cells in adults with established prior immunity. Therefore, viral vectors or peptide approaches are key to harnessing T cell responses. A plethora of viral vector vaccines and routes of administration may be needed for next generation vaccine strategies that require repeated long-term administration to overcome vector immunity and increase our arsenal against diverse influenza viruses.
Enhanced Single and Simultaneous As(III) Adsorption in Pearl River Delta Water by Hexylamine Functionalized Vermiculite
Authors: Ahmed Zubair , Wu Pingxiao , Xu Yijing , Keerio Hareef Ahmed , Wu Jiayan , Ye Quanyun , Niu Wenchao , Chen Meiqing , Dang Zhi
Published: September 2021

Enhanced As(III) removal (>99.7) was achieved by a novel organoclay (HEX-VER) adsorbent in Pearl River Delta water. Single and simultaneous As(III) removal in the presence of Cd(II) and/or Pb(II) by batch adsorption tests was analyzed. Spectroscopic, spectrometric, microscopic, and potentiometric techniques were used for characterization of the adsorbents. The parameters affecting As(III) adsorption, including pH, kinetic, isotherm, thermodynamic, and co-existing ions (Cl−, F−, NO3−, CO32−, SO42−, Ca2+ and Mg2+) were also investigated. The results showed that HEX-VER owned different morphology and larger average pore diameter after functionalization, resulting in an improvement of As (III) adsorption capacity. Further analysis confirmed that adsorption was of the monomolecular layer, well-described by the Langmuir isotherm model. The dominant mechanisms for As(III) removal were ion-exchange and complexation. Moreover, HEX-VER was regenerated for five consecutive cycles, and the removal ratio was ≈ 92%, showing its great regeneration potential. These findings suggest that the proposed inexpensive adsorbent has potential for practical applications of As(III) removal from river water.
Water Infrastructure Development in Nigeria: Trend, Size, and Purpose
Authors: Adeniran Adegboyega , Daniell Katherine A. , Pittock Jamie
Published: September 2021

Water infrastructure development is key to attaining sustainable development, especially for water supply, sanitation and health, agricultural development, and energy production. However, sub-Saharan African countries face specific challenges around infrastructure financing, systemic and repeated malfunctioning, and decentralised infrastructure types. Using Nigeria as a case, this article aims to analyse historical water infrastructure development in Nigeria with a specific focus on dams and standpipes. Seven themes are discussed: infrastructure divisions; deprioritising water supply; political infrastructures; infrastructure failure and sustainability; infrastructure classification and typologies; optimal use of water resources and infrastructure; and a commentary on the future of water infrastructure development. The article concludes with policy and research suggestions for policymakers and other relevant stakeholders.
CFD Model of the Density-Driven Bidirectional Flows through the West Crack Breach in the Great Salt Lake Causeway
Authors: Rasmussen Michael , Dutta Som , Neilson Bethany T. , Crookston Brian Mark
Published: September 2021

Stratified flows and the resulting density-driven currents occur in the natural environment and commonly in saline lakes. In the Great Salt Lake, Utah, USA, the northern and southern portions of the lake are divided by an east-to-west railroad causeway that disrupts natural lake currents and significantly increases salt concentrations in the northern section. To support management efforts focused on addressing rising environmental and economic concerns associated with varied saltwater densities throughout the lake, the causeway was recently modified to include a new breach. The purpose of this new breach is to enhance salt exchange between the northern and southern sections of the lake. Since construction, it typically exhibits a strong density-driven bidirectional flow pattern, but estimating flows and salt exchange has proven to be difficult. To obtain much needed insights into the ability of this hydraulic structure to exchange water and salt between the two sections of the lake, a field campaign coupled with CFD modeling was undertaken. Results from this study indicate that the vertical velocity profile in the breach is sensitive to density differences between flow layers along with breach geometry and water surface elevations. The CFD model was able to accurately represent the bidirectional flows through the breach and provides for improved estimates of water and salt exchanges between the north and south sections of the lake.
Effects of Climate Change on Water Quality in the Jucar River Basin (Spain)
Authors: Gómez-Martínez Gabriel , Galiano Lorena , Rubio Toni , Prado-López Carlos , Redolat Darío , Paradinas Blázquez César , Gaitán Emma , Pedro-Monzonís María , Ferriz-Sánchez Sergio , Añó Soto Miguel , Monjo Robert , Pérez-Martín Miguel Ángel , Almenar Llorens Pura , Macián Cervera Javier
Published: September 2021

The Mediterranean region is a climate change hotspot, especially concerning issues of hydrological planning and urban water supply systems. In this context, the Jucar River Basin (Spain) presents an increase of frequency, intensity and duration of extreme meteorological phenomena, such as torrential rains, droughts or heat waves, which directly affect the quantity and quality of raw water available for drinking. This paper aims to analyze the effects of climate change on the raw water quality of the Jucar River Basin District, which mainly supplies the city of Valencia and its metropolitan area, in order to adapt drinking water treatments to new conditions and opportunities. For this purpose, we used observed data of water quality parameters from four stations and climate drivers from seven Earth system models of the latest Coupled Model Intercomparison Project—Phase 6. To model water quality (turbidity and conductivity) in the past and future scenarios, this study employs a backward stepwise regression taking into account daily values of mean temperature, maximum temperature, total rainfall and minimum and maximum relative humidity. Results showed that the model performance of the water quality simulation is more adequate for short moving-average windows (about 2–7 days) for turbidity and longer windows (about 30–60 days) for conductivity. Concerning the future scenarios, the most significant change was found in the projected increase of conductivity for the station of the Júcar river, between 4 and 11% by 2100, respectively, under the medium (SSP2–4.5) and pessimistic (SSP5–8.5) emission scenarios. The joint use of these types of management and monitoring tools may help the managers in charge of carrying out the different water treatments needed to apply a better plan to raw water and may help them identify future threats and investment needs to adapt the urban water supply systems to the changing conditions of raw water, such as turbidity or conductivity, as a consequence of climate change.
Ensemble Projection of Future Climate and Surface Water Supplies in the North Saskatchewan River Basin above Edmonton, Alberta, Canada
Authors: Anis Muhammad Rehan , Sauchyn David J.
Published: September 2021

Changes in temperature and precipitation are expected to alter the seasonal distribution of surface water supplies in snowmelt-dominated watersheds. A realistic assessment of future climate change and inter-annual variability is required to meet a growing demand for water supplies in all major use sectors. This study focuses on changes in climate and runoff in the North Saskatchewan River Basin (NSRB) above Edmonton, AB, Canada, using the MESH (Modélisation Environnementale communautaire—Surface Hydrology) model. The bias-corrected ensemble of Canadian Regional Climate Model (CanRCM4) data is used to drive MESH for two 60-year time periods, a historical baseline (1951–2010) and future projection (2041–2100), under Representative Concentration Pathway (RCP) 8.5. The precipitation is projected to increase in every season, there is significant trend in spring (0.62) and fall (0.41) and insignificant in summer (0.008). Winter extreme minimum temperature and summer extreme maximum temperature are increasing by 2–3 °C in the near future and 5–6 °C in the far future. Annual runoff increases by 19% compared to base period. The results reveal long-term hydrological variability enabling water resource managers to better prepare for climate change and extreme events to build more resilient systems for future water demand in the NSRB.
Analysis and Model of River Basin Sustainable Management by SWOT and AHP Methods
Authors: Bakalár Tomáš , Pavolová Henrieta , Tokarčík Alexander
Published: September 2021

The sustainable management of river basins is a comprehensive problem involving not only environmental quality but also socio-economic aspects. The primary objective of the study is to propose a sustainable management model of a river basin based on a clear identification of the good water quality in the river basin applicable for any river basin. The proposal is based on a monitoring of the quality of surface water in the basin, a quantitative and qualitative analysis of pollution, a questionnaire survey on the sewer systems and wastewater treatment in the basin and the diffuse sources of water pollution. For a better outline, a case study of Hornád river basin, Slovakia, was carried out. Two methodologies were applied: SWOT analysis for identification of indicators and the priorities and AHP analysis for a prioritization of the decisions. These analyses can be carried out for any activity based on identification of indicators and the priorities of the defined indicators to promote sustainable development. Based on the findings and the results of the analyses the model for managing the development of surface water quality in the basin was proposed. Generally applicable principles of sustainable development, accepting legislation in the field of water management, considering the quality of surface water in the basin, the impacts of wastewater discharges into the recipient, the identification and evaluation of positive and negative aspects of surface water quality, and the implementation of the proposed measures and post-implementation monitoring of qualitative development were covered in and by the proposed model.