Publications by authors named "Gabriel Gonzalez"

114 Publications

Children's perceptions of their parent's parenting strategies and child influence on purchases in a supermarket.

Appetite 2021 Jul 4;162:105149. Epub 2021 Feb 4.

San Diego State University, College of Health and Human Services, School of Public Health and the Institute for Behavioral and Community Health, 9245 Sky Park Court, Suite 221, San Diego, CA, 92123, USA. Electronic address:

This field study identified, through observation, child influence on food and beverage purchases within a supermarket, as well as the influence of the children's perceptions of their parents' parenting strategies related to eating behaviors on these purchases. Four supermarkets were recruited to participate and agreed to allow recruitment of parent-child dyads and implementation of data collection protocols within their stores. Parent-child (7-14 yo) dyads were recruited to wear eye-tracking glasses during the supermarket visit, complete separate individual interviews, and have their store receipts scanned. The receipt data provided evidence of what was purchased, including overall purchases, as well as purchases of energy-dense, nutrient-poor foods and beverages. The eye-tracking data, together with the receipt data, identified which items were requested by the child and purchased. The child interviews provided the child's perceptions of parenting strategies (i.e., parental monitoring, control). Seventy-six dyads agreed to participate and completed the study protocols. During most of the shopping trips, items were purchased as a result of child-initiated request interactions. Children's perceptions of their parent's use of monitoring was consistently associated with fewer purchases overall and of energy-dense, nutrient-poor items, and with reduced child influence on what was purchased.
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http://dx.doi.org/10.1016/j.appet.2021.105149DOI Listing
July 2021

Novel pentacyclic triterpenes exhibiting strong neuroprotective activity in SH-SY5Y cells in salsolinol- and glutamate-induced neurodegeneration models.

Eur J Med Chem 2021 Mar 16;213:113168. Epub 2021 Jan 16.

Laboratory of Growth Regulators, Faculty of Science, Palacký University and the Institute of Experimental Botany of the Czech Academy of Sciences, Šlechtitelů 27, CZ-78371, Olomouc, Czech Republic; Department of Neurology, University Hospital Olomouc and Faculty of Medicine and Dentistry, Palacký University Olomouc, CZ-775 20, Olomouc, Czech Republic. Electronic address:

Novel triterpene derivatives were prepared and evaluated in salsolinol (SAL)- and glutamate (Glu)-induced models of neurodegeneration in neuron-like SH-SY5Y cells. Among the tested compounds, betulin triazole 4 bearing a tetraacetyl-β-d-glucose substituent showed a highly potent neuroprotective effect. Further studies revealed that removal of tetraacetyl-β-d-glucose part (free triazole derivative 10) resulted in strong neuroprotection in the SAL model at 1 μM, but this derivative suffered from cytotoxicity at higher concentrations. Both compounds modulated oxidative stress and caspase-3,7 activity, but 10 showed a superior effect comparable to the Ac-DEVD-CHO inhibitor. Interestingly, while both 4 and 10 outperformed the positive controls in blocking mitochondrial permeability transition pore opening, only 4 demonstrated potent restoration of the mitochondrial membrane potential (MMP) in the model. Derivatives 4 and 10 also showed neuroprotection in the Glu model, with 10 exhibiting the strongest oxidative stress reducing effect among the tested compounds, while the neuroprotective activity of 4 was probably due recovery of the MMP.
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http://dx.doi.org/10.1016/j.ejmech.2021.113168DOI Listing
March 2021

Cytoprotective activities of kinetin purine isosteres.

Bioorg Med Chem 2021 Mar 6;33:115993. Epub 2021 Jan 6.

Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, Olomouc CZ-77515, Czech Republic; Laboratory of Growth Regulators, Palacký University & Institute of Experimental Botany AS CR, Šlechtitelů 27, Olomouc CZ-78371, Czech Republic. Electronic address:

Kinetin (N-furfuryladenine), a plant growth substance of the cytokinin family, has been shown to modulate aging and various age-related conditions in animal models. Here we report the synthesis of kinetin isosteres with the purine ring replaced by other bicyclic heterocycles, and the biological evaluation of their activity in several in vitro models related to neurodegenerative diseases. Our findings indicate that kinetin isosteres protect Friedreich́s ataxia patient-derived fibroblasts against glutathione depletion, protect neuron-like SH-SY5Y cells from glutamate-induced oxidative damage, and correct aberrant splicing of the ELP1 gene in fibroblasts derived from a familial dysautonomia patient. Although the mechanism of action of kinetin derivatives remains unclear, our data suggest that the cytoprotective activity of some purine isosteres is mediated by their ability to reduce oxidative stress. Further, the studies of permeation across artificial membrane and model gut and blood-brain barriers indicate that the compounds are orally available and can reach central nervous system. Overall, our data demonstrate that isosteric replacement of the kinetin purine scaffold is a fruitful strategy for improving known biological activities of kinetin and discovering novel therapeutic opportunities.
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http://dx.doi.org/10.1016/j.bmc.2021.115993DOI Listing
March 2021

Cytokinin Plant Hormones Have Neuroprotective Activity in In Vitro Models of Parkinson's Disease.

Molecules 2021 Jan 12;26(2). Epub 2021 Jan 12.

Laboratory of Growth Regulators, Institute of Experimental Botany of the Czech Academy of Sciences, and Faculty of Science, Palacký University, Šlechtitelů 27, CZ-78371 Olomouc, Czech Republic.

Cytokinins are adenine-based phytohormones that regulate key processes in plants, such as cell division and differentiation, root and shoot growth, apical dominance, branching, and seed germination. In preliminary studies, they have also shown protective activities against human neurodegenerative diseases. To extend knowledge of the protection (protective activity) they offer, we investigated activities of natural cytokinins against salsolinol (SAL)-induced toxicity (a Parkinson's disease model) and glutamate (Glu)-induced death of neuron-like dopaminergic SH-SY5Y cells. We found that kinetin-3-glucoside, -zeatin riboside, and N-isopentenyladenosine were active in the SAL-induced PD model. In addition, -, -zeatin, and kinetin along with the iron chelator deferoxamine (DFO) and the necroptosis inhibitor necrostatin 1 (NEC-1) significantly reduced cell death rates in the Glu-induced model. Lactate dehydrogenase assays revealed that the cytokinins provided lower neuroprotective activity than DFO and NEC-1. Moreover, they reduced apoptotic caspase-3/7 activities less strongly than DFO. However, the cytokinins had very similar effects to DFO and NEC-1 on superoxide radical production. Overall, they showed protective activity in the SAL-induced model of parkinsonian neuronal cell death and Glu-induced model of oxidative damage mainly by reduction of oxidative stress.
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http://dx.doi.org/10.3390/molecules26020361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827283PMC
January 2021

Population-Specific Single-Nucleotide Polymorphisms Have Limited Impact on SARS-CoV-2 Infectivity In Vitro.

Viruses 2021 Jan 6;13(1). Epub 2021 Jan 6.

Laboratory of Emerging Viral Diseases, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Osaka 565-0871, Japan.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), employs host-cell angiotensin-converting enzyme 2 (ACE2) for cell entry. Genetic analyses of have identified several single-nucleotide polymorphisms (SNPs) specific to different human populations. Molecular dynamics simulations have indicated that several of these SNPs could affect interactions between SARS-CoV-2 and ACE2, thereby providing a partial explanation for the regional differences observed in SARS-CoV-2 infectivity and severity. However, the significance of population-specific SNPs in SARS-CoV-2 infectivity is unknown, as no in vitro validation studies have been performed. Here, we analyzed the impact of eight SNPs found in specific populations on receptor binding and cell entry in vitro. Except for a SNP causing a nonsense mutation that reduced ACE2 expression, none of the selected SNPs markedly altered the interaction between ACE2 and the SARS-CoV-2 spike protein (SARS-2-S), which is responsible for receptor recognition and cell entry, or the efficiency of viral cell entry mediated by SARS-2-S. Our findings indicate that polymorphisms have limited impact on the ACE2-dependent cell entry of SARS-CoV-2 and underscore the importance of future studies on the involvement of population-specific SNPs of other host genes in susceptibility toward SARS-CoV-2 infection.
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http://dx.doi.org/10.3390/v13010067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825141PMC
January 2021

Bioactive Steroids from the Red Sea Soft Coral .

Mar Drugs 2020 Dec 10;18(12). Epub 2020 Dec 10.

Section of Pharmacognosy and Chemistry of Natural Products, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece.

Six new (, , , , and ) and twenty previously isolated (-, , -, -, and -) steroids featuring thirteen different carbocycle motifs were isolated from the organic extract of the soft coral collected from the Hurghada reef in the Red Sea. The structures and the relative configurations of the isolated natural products have been determined based on extensive analysis of their NMR and MS data. The cytotoxic, anti-inflammatory, anti-angiogenic, and neuroprotective activity of compounds -, -, -, and -, as well as their effect on androgen receptor-regulated transcription was evaluated in vitro in human tumor and non-cancerous cells. Steroids and showed significant cytotoxicity in the low micromolar range against the HeLa and MCF7 cancer cell lines, while migration of endothelial cells was inhibited by compounds , , and at 20 µM. The results of the androgen receptor (AR) reporter assay showed that compound exhibited the strongest inhibition of AR at 10 µM, while it is noteworthy that steroids , and displayed increased inhibition of AR with decreasing concentrations. Additionally, compounds and showed neuroprotective activity on neuron-like SH-SY5Y cells.
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http://dx.doi.org/10.3390/md18120632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763444PMC
December 2020

Host-directed editing of the SARS-CoV-2 genome.

Biochem Biophys Res Commun 2021 01 5;538:35-39. Epub 2020 Nov 5.

King Abdullah University of Science and Technology (KAUST), Pathogen Genomics Laboratory, Biological and Environmental Science and Engineering (BESE), Thuwal-Jeddah, 23955-6900, Saudi Arabia; Research Center for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, N20 W10 Kita-ku, Sapporo, 001-0020, Japan. Electronic address:

The extensive sequence data generated from SARS-CoV-2 during the 2020 pandemic has facilitated the study of viral genome evolution over a brief period of time. This has highlighted instances of directional mutation pressures exerted on the SARS-CoV-2 genome from host antiviral defense systems. In this brief review we describe three such human defense mechanisms, the apolipoprotein B mRNA editing catalytic polypeptide-like proteins (APOBEC), adenosine deaminase acting on RNA proteins (ADAR), and reactive oxygen species (ROS), and discuss their potential implications on SARS-CoV-2 evolution.
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http://dx.doi.org/10.1016/j.bbrc.2020.10.092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643664PMC
January 2021

The synthesis and cholinesterase inhibitory activities of solasodine analogues with seven-membered F ring.

J Steroid Biochem Mol Biol 2021 Jan 28;205:105776. Epub 2020 Oct 28.

Faculty of Chemistry, University of Białystok, K. Ciołkowskiego 1K, 15-245, Białystok, Poland. Electronic address:

Solasodine analogues containing a seven-membered F ring with a nitrogen atom placed at position 22a were prepared from diosgenin or tigogenin in a four-step synthesis comprising of the simultaneous opening of the F-ring and introduction of cyanide in position 22α, activation of the 26-hydroxyl group as mesylate, nitrile reduction, and N-cyclization. Solasodine, six obtained 22a(N)-homo analogues, as well as four 26a-homosolasodine derivatives and their open-chain precursors (13 in total) were tested as potential inhibitors of acetyl- and butyryl-cholinesterases and showed activity at micromolar concentrations. The structure-activity relationship study revealed that activities against studied esterases are affected by the structure of E/F rings and the substitution pattern of ring A. The most potent compound 8 acted as non-competitive inhibitors and exerted IC = 8.51 μM and 7.05 μM for eeAChE and eqBChE, respectively. Molecular docking studies revealed the hydrogen bond interaction of 8 with S293 of AChE; further rings are stabilized via hydrophobic interaction (ring A) or interaction with Y341 and W286 (rings B and C). Biological experiments showed no neurotoxicity of differentiated SH-SY5Y cells. More importantly, results from neuroprotective assay based on glutamate-induced cytotoxicity revealed that most derivatives had the ability to increase the viability of differentiated SH-SY5Y cells in comparison to galantamine and lipoic acid assayed as standards. The newly synthesized solasodine analogues are able to inhibit and to bind cholinesterases in noncompetitive mode of inhibition and exhibited neuroprotection potential of differentiated neuroblastoma cells after Glu-induced toxicity.
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http://dx.doi.org/10.1016/j.jsbmb.2020.105776DOI Listing
January 2021

Whole-genome sequencing to track SARS-CoV-2 transmission in nosocomial outbreaks.

Clin Infect Dis 2020 Sep 19. Epub 2020 Sep 19.

Department of Microbiology, St. Vincent's University Hospital, School of Medicine, University College Dublin, Dublin, Ireland.

Background: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthcare institutions posed a significant problem. Due to limited evidence, guidance on appropriate infection prevention and control (IPC) measures such as the wearing of face masks varied. Here, we applied whole virus genome sequencing (WvGS) to analyse transmission routes of SARS-CoV-2 in hospital-acquired (HA) COVID-19.

Methods: An investigation was undertaken for all HA cases of COVID-19 from March to April 2020. Fifty SARS-CoV-2 samples were analysed by WvGS and their phylogenetic relationship established.

Results: WvGS identified transmission events previously undetected by epidemiological analysis and provided evidence for SARS-CoV-2 transmission between healthcare workers (HCW) and patients and among HCW themselves. The majority of HA COVID-19 cases occurred in patients highly dependent on nursing care, suggesting the likely route of transmission was by close contact or droplet, rather than aerosol, transmission. Mortality among HA COVID-19 infections was recorded as 33%.

Conclusions: This study provides evidence that SARS-CoV-2 transmission occurs from symptomatic and asymptomatic HCWs to patients. Interventions including comprehensive screening of HCWs for COVID-19 symptoms, PCR testing of asymptomatic HCWs upon identification of HA cases and implementation of universal use of surgical masks for all clinical care is indicated to prevent viral transmission. Our study highlights the importance of close collaboration between guidance bodies and frontline IPC experts for developing control measures in an emergency pandemic situation caused by a virus with undefined transmission modus.
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http://dx.doi.org/10.1093/cid/ciaa1433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543366PMC
September 2020

Co-Circulation of Multiple Serotypes of Bluetongue Virus in Zambia.

Viruses 2020 08 31;12(9). Epub 2020 Aug 31.

Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan.

Bluetongue (BT) is an arthropod-borne viral disease of ruminants with serious trade and socio-economic implications. Although the disease has been reported in a number of countries in sub-Saharan Africa, there is currently no information on circulating serotypes and disease distribution in Zambia. Following surveillance for BT in domestic and wild ruminants in Zambia, BT virus (BTV) nucleic acid and antibodies were detected in eight of the 10 provinces of the country. About 40% (87/215) of pooled blood samples from cattle and goats were positive for BTV nucleic acid, while one hartebeest pool (1/43) was positive among wildlife samples. Sequence analysis of segment 2 revealed presence of serotypes 3, 5, 7, 12 and 15, with five nucleotypes (B, E, F, G and J) being identified. Segment 10 phylogeny showed Zambian BTV sequences clustering with Western topotype strains from South Africa, intimating likely transboundary spread of BTV in Southern Africa. Interestingly, two Zambian viruses and one isolate from Israel formed a novel clade, which we designated as Western topotype 4. The high seroprevalence (96.2%) in cattle from Lusaka and Central provinces and co-circulation of multiple serotypes showed that BT is widespread, underscoring the need for prevention and control strategies.
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http://dx.doi.org/10.3390/v12090963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552058PMC
August 2020

Characterization of mammalian orthoreoviruses isolated from faeces of pigs in Zambia.

J Gen Virol 2020 10 24;101(10):1027-1036. Epub 2020 Jul 24.

Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University Kita-ku, Sapporo, 001-0020, Japan.

Mammalian orthoreovirus (MRV) has been identified in humans, livestock and wild animals; this wide host range allows individual MRV to transmit into multiple species. Although several interspecies transmission and genetic reassortment events of MRVs among humans, livestock and wildlife have been reported, the genetic diversity and geographic distribution of MRVs in Africa are poorly understood. In this study, we report the first isolation and characterization of MRVs circulating in a pig population in Zambia. In our screening, MRV genomes were detected in 19.7 % (29/147) of faecal samples collected from pigs by reverse transcription PCR. Three infectious MRV strains (MRV-85, MRV-96 and MRV-117) were successfully isolated, and their complete genomes were sequenced. Recombination analyses based on the complete genome sequences of the isolated MRVs demonstrated that MRV-96 shared the S3 segment with a different MRV isolated from bats, and that the L1 and M3 segments of MRV-117 originated from bat and human MRVs, respectively. Our results suggest that the isolated MRVs emerged through genetic reassortment events with interspecies transmission. Given the lack of information regarding MRVs in Africa, further surveillance of MRVs circulating among humans, domestic animals and wildlife is required to assess potential risk for humans and animals.
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http://dx.doi.org/10.1099/jgv.0.001476DOI Listing
October 2020

Bat-borne polyomaviruses in Europe reveal an evolutionary history of intrahost divergence with horseshoe bats distributed across the African and Eurasian continents.

J Gen Virol 2020 10 9;101(10):1119-1130. Epub 2020 Jul 9.

National Virus Reference Laboratory, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.

Polyomaviruses (PyVs) are small, circular dsDNA viruses carried by diverse vertebrates, including bats. Although previous studies have reported several horseshoe bat PyVs collected in Zambia and China, it is still unclear how PyVs evolved in this group of widely dispersed mammals. Horseshoe bats (genus ) are distributed across the Old World and are natural reservoirs of numerous pathogenic viruses. Herein, non-invasive bat samples from European horseshoe bat species were collected in Hungary for PyV identification and novel PyVs with complete genomes were successfully recovered from two different European horseshoe bat species. Genomic and phylogenetic analysis of the Hungarian horseshoe bat PyVs supported their classification into the genera and . Notably, despite the significant geographical distances between the corresponding sampling locations, Hungarian PyVs exhibited high genetic relatedness with previously described Zambian and Chinese horseshoe bat PyVs, and phylogenetically clustered with these viruses in each PyV genus. Correlation and virus-host relationship analysis suggested that these PyVs co-diverged with their European, African and Asian horseshoe bat hosts distributed on different continents during their evolutionary history. Additionally, assessment of selective pressures over the major capsid protein (VP1) of horseshoe bat PyVs showed sites under positive selection located in motifs exposed to the exterior of the capsid. In summary, our findings revealed a pattern of stable intrahost divergence of horseshoe bat PyVs with their mammalian hosts on the African and Eurasian continents over evolutionary time.
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http://dx.doi.org/10.1099/jgv.0.001467DOI Listing
October 2020

Evidence for exposure of asymptomatic domestic pigs to African swine fever virus during an inter-epidemic period in Zambia.

Transbound Emerg Dis 2020 Nov 2;67(6):2741-2752. Epub 2020 Jun 2.

Division of Molecular Pathobiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.

African swine fever (ASF) causes persistent outbreaks in endemic and non-endemic regions in Zambia. However, the epidemiology of the disease is poorly understood, particularly during the inter-epidemic periods. We conducted surveillance for ASF in asymptomatic domestic pigs and soft ticks in selected Zambian provinces. While serum samples (n = 1,134) were collected from crossbred pigs from all study sites between 2014 and 2017, whole blood (n = 300) was collected from both crossbred and indigenous pigs in Eastern Province (EP) in 2017. Soft ticks were collected from Mosi-oa-Tunya National Park in Southern Province (SP) in 2019. Sera were screened for antibodies against ASF by ELISA while genome detection in whole blood and soft ticks was conducted by PCR. Ticks were identified morphologically and by phylogenetic analysis of the 16S rRNA gene. Seroprevalence was highest in EP (50.9%, 95% CI [47.0-54.9]) compared to significantly lower rates in SP (2.9%, 95% CI [1.6-5.1]). No antibodies to ASFV were detected in Lusaka Province. In EP, the prevalence of ASFV genome was 11.7% (35/300), significantly higher (OR = 6.2, 95% CI [2.4-16.6]) in indigenous pigs compared to crossbred pigs. The pooled prevalence of ASFV genome in ticks was 11.0%, 95% CI [8.5-13.9]. Free-range husbandry system was the only factor that was significantly associated with seropositive (p < .0001, OR = 39.3) and PCR-positive results (p < .001, OR = 5.7). Phylogenetically, based on the p72 gene, ASFV from Ornithodoros moubata ticks detected in this study belonged to genotype I, but they separated into two distinct clusters. Besides confirming ASF endemicity in EP and the presence of ASFV-infected ticks in SP, these results provide evidence for exposure of domestic pigs to ASFV in non-endemic regions during the inter-epidemic period.
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http://dx.doi.org/10.1111/tbed.13630DOI Listing
November 2020

Genomic and phylogenetic analysis of two guinea pig adenovirus strains recovered from archival lung tissue.

Virus Res 2020 08 18;285:197965. Epub 2020 Apr 18.

Lovelace Respiratory Research Institute, Albuquerque, NM, USA. Electronic address:

Next generation sequencing was used to determine the whole genome sequence for two different strains of guinea pig adenovirus (GPAdV) detected in association with outbreaks of pneumonia in Australia in 1996, and in Germany in 1997 using total DNA extracted from infected archival frozen lung tissue as a template. The length of the determined genomic sequences was 37,031 bp and 37,070 bp, respectively. The nucleotide composition showed a relatively high content of guanine + cytosine (G + C) of 62 %. The 99.6 % nucleotide identity between the two sequenced viruses suggests that they may represent variants of the same genotype. The GPAdV genome exhibits the genomic features of a typical mastadenovirus with at least 32 open reading frames identified. Five novel open reading frames were found at the right end of the genomic sequence. One of them maps to the predicted E3 region and encodes a putative CR1 protein, two map to the E4 region, and two map to the l strand of L1 and L3, respectively. Our phylogenetic analysis of whole genome sequences showed that among the mammalian AdV species described to date, GPAdV is most closely related to MAdV-2 The characterization of this mastadenovirus species offers an opportunity to develop a new small animal model to study mammalian adenovirus pathogenesis.
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http://dx.doi.org/10.1016/j.virusres.2020.197965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363042PMC
August 2020

Isolation and initial propagation of guinea pig adenovirus (GPAdV) in cell lines.

F1000Res 2019 5;8:1597. Epub 2019 Sep 5.

Lovelace Respiratory Research Institute, Albuquerque, New Mexico, 87108, USA.

 The lack of adequate systems to isolate and propagate guinea pig adenovirus (GPAdV), a prevalent cause of respiratory illness of varaible severity in laboratory guinea pig colonies worldwide, has precluded its formal characterization to allow for the development of comprehensive diagnostic assays, and for the execution of complex pathogenesis and basic virology studies. Two strains of GPAdV were isolated in guinea pig ( ) cell cultures from frozen archival infected animal tissue originated from colony outbreaks of pneumonia in Australia and the Czech Republic in 1996. Commercially available guinea pig cell lines from colorectal carcinoma (GPC-16), fetal fibroblast (104-C1) and lung fibroblast (JH4 C1), and the tracheal epithelial cell line GPTEC-T developed in this study were able to support viral infection and early propagation. Sufficient viral DNA was recovered from cell cultures to PCR-amplify and obtain sequence data for the complete hexon gene and partial DNA polymerase and penton base genes. Phylogenetic analysis for the three regions of the genome provided strong evidence confirming GPAdV as a unique species in the genus Mastadenovirus. This study demonstrated the feasibility of propagating GPAdV in cultures of immortalized lines of GP cells of a variety of types, thus establishing a critical foundation for the development of a robust culture platform for virus stock production and titration. The generation and analysis of whole GPAdV genome sequences will provide additional data for a comprehensive description of the genetic organization of the viral genome and for a better assessment of genetic diversity between the two isolated strains.
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http://dx.doi.org/10.12688/f1000research.20135.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096189PMC
June 2020

Extensive Genetic Diversity of Polyomaviruses in Sympatric Bat Communities: Host Switching versus Coevolution.

J Virol 2020 04 16;94(9). Epub 2020 Apr 16.

Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin Province, China

Polyomaviruses (PyVs) are small DNA viruses carried by diverse vertebrates. The evolutionary relationships of viruses and hosts remain largely unclear due to very limited surveillance in sympatric communities. In order to investigate whether PyVs can transmit among different mammalian species and to identify host-switching events in the field, we conducted a systematic study of a large collection of bats ( = 1,083) from 29 sympatric communities across China which contained multiple species with frequent contact. PyVs were detected in 21 bat communities, with 192 PyVs identified in 186 bats from 15 species within 6 families representing at least 28 newly described PyVs. Surveillance results and phylogenetic analyses surprisingly revealed three interfamily PyV host-switching events in these sympatric bat communities: two distinct PyVs were identified in two bat species in restricted geographical locations, while another PyV clustered phylogenetically with PyVs carried by bats from a different host family. Virus-host relationships of all discovered PyVs were also evaluated, and no additional host-switching events were found. PyVs were identified in different horseshoe bat species in sympatric communities without observation of host-switching events, showed high genomic identities, and clustered with each other. This suggested that even for PyVs with high genomic identities in closely related host species, the potential for host switching is low. In summary, our findings revealed that PyV host switching in sympatric bat communities can occur but is limited and that host switching of bat-borne PyVs is relatively rare on the predominantly evolutionary background of codivergence with their hosts. Since the discovery of murine polyomavirus in the 1950s, polyomaviruses (PyVs) have been considered highly host restricted in mammals. Sympatric bat communities commonly contain several different bat species in an ecological niche facilitating viral transmission, and they therefore represent a model to identify host-switching events of PyVs. In this study, we screened PyVs in a large number of bats in sympatric communities from diverse habitats across China. We provide evidence that cross-species bat-borne PyV transmission exists, though is limited, and that host-switching events appear relatively rare during the evolutionary history of these viruses. PyVs with close genomic identities were also identified in different bat species without host-switching events. Based on these findings, we propose an evolutionary scheme for bat-borne PyVs in which limited host-switching events occur on the background of codivergence and lineage duplication, generating the viral genetic diversity in bats.
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http://dx.doi.org/10.1128/JVI.02101-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163151PMC
April 2020

Connected Elbow Exoskeleton System for Rehabilitation Training Based on Virtual Reality and Context-Aware.

Sensors (Basel) 2020 Feb 6;20(3). Epub 2020 Feb 6.

Expert Systems and Applications Lab, Faculty of Science, University of Salamanca, Plaza de los Caídos s/n, 37002 Salamanca, Spain.

Traditional physiotherapy rehabilitation systems are evolving into more advanced systems based on exoskeleton systems and Virtual Reality (VR) environments that enhance and improve rehabilitation techniques and physical exercise. In addition, due to current connected systems and paradigms such as the Internet of Things (IoT) or Ambient Intelligent (AmI) systems, it is possible to design and develop advanced, effective, and low-cost medical tools that patients may have in their homes. This article presents a low-cost exoskeleton for the elbow that is connected to a Context-Aware architecture and thanks to a VR system the patient can perform rehabilitation exercises in an interactive way. The integration of virtual reality technology in rehabilitation exercises provides an intensive, repetitive and task-oriented capacity to improve patient motivation and reduce work on medical professionals. One of the system highlights is the intelligent ability to generate new exercises, monitor the exercises performed by users in search of progress or possible problems and the dynamic modification of the exercises characteristics. The platform also allows the incorporation of commercial medical sensors capable of collecting valuable information for greater accuracy in the diagnosis and evolution of patients. A case study with real patients with promising results has been carried out.
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http://dx.doi.org/10.3390/s20030858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038710PMC
February 2020

Genetic and Biological Diversity of Porcine Sapeloviruses Prevailing in Zambia.

Viruses 2020 02 5;12(2). Epub 2020 Feb 5.

Department of Disease Control, School of Veterinary Medicine, the University of Zambia, P.O. Box 32379, Lusaka 10101, Zambia.

Porcine sapelovirus (PSV) has been detected worldwide in pig populations. Although PSV causes various symptoms such as encephalomyelitis, diarrhea, and pneumonia in pigs, the economic impact of PSV infection remains to be determined. However, information on the distribution and genetic diversity of PSV is quite limited, particularly in Africa. In this study, we investigated the prevalence of PSV infection in Zambia and characterized the isolated PSVs genetically and biologically. We screened 147 fecal samples collected in 2018 and found that the prevalences of PSV infection in suckling pigs and fattening pigs were high (36.2% and 94.0%, respectively). Phylogenetic analyses revealed that the Zambian PSVs were divided into three different lineages (Lineages 1-3) in the clade consisting of Chinese strains. The Zambian PSVs belonging to Lineages 2 and 3 replicated more efficiently than those belonging to Lineage 1 in Vero E6 and BHK cells. Bioinformatic analyses revealed that genetic recombination events had occurred and the recombination breakpoints were located in the L and 2A genes. Our results indicated that at least two biologically distinct PSVs could be circulating in the Zambian pig population and that genetic recombination played a role in the evolution of PSVs.
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http://dx.doi.org/10.3390/v12020180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077239PMC
February 2020

Pediatric Infections by Types 2, 89, and a Recombinant Type Detected in Japan between 2011 and 2018.

Viruses 2019 12 6;11(12). Epub 2019 Dec 6.

Division 4, Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.

Between 2011 and 2018, 518 respiratory adenovirus infections were diagnosed in a pediatric clinic in Shizuoka, Japan. Detection and typing were performed by partial sequencing of both hexon- and fiber-coding regions which identified: adenovirus type 1 (Ad-1, = 85), Ad-2 ( = 160), Ad-3 ( = 193), Ad-4 ( = 18), Ad-5 ( = 27), Ad-11 ( = 2), Ad-54 ( = 3), and Ad-56 ( = 1). Considering previous reports of the circulation of an endemic recombinant Ad-2, e.g., Ad-89, 100 samples typed as Ad-2 were randomly selected for further molecular typing by sequencing the penton base-coding region. Despite the high nucleotide sequence conservation in the penton base- coding region, 27 samples showed 98% identity to Ad-2. Furthermore, 14 samples showed 97.7% identity to Ad-2 and 99.8% identity to Ad-89, while the remaining 13 samples showed an average 98% pairwise identity to other Ad-C types and clustered with Ad-5. The samples typed as Ad-89 ( = 14) and as a recombinant Ad type (P5H2F2) ( = 13) represented 27% of cases originally diagnosed as Ad-2, and were detected sporadically. Therefore, two previously uncharacterized types in Japan, Ad-89 and a recombinant Ad-C, were shown to circulate in children. This study creates a precedent to evaluate the epidemiology and divergence among Ad-C types by comprehensively considering the type classification of adenoviruses.
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http://dx.doi.org/10.3390/v11121131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950085PMC
December 2019

Disinfectant potential in inactivation of epidemic keratoconjunctivitis-related adenoviruses by potassium peroxymonosulfate.

Eur J Ophthalmol 2019 Dec 9:1120672119891408. Epub 2019 Dec 9.

Division of Signalling in Cancer and Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.

Purpose: The aim of this study was to test the antiviral effectivity of potassium peroxymonosulfate (RUBYSTA, KYORIN) against five epidemic keratoconjunctivitis-related types of in vitro.

Methods: Five types of (8, 37, 53, 54 and 56) were incubated with 1% potassium peroxymonosulfate, 0.1% sodium hypochlorite (NaClO) or alcohol-based disinfectant for 30 s or 1 min. These solutions were subjected to measurements of viral titres by infection assays in A549 cells. At day 6 post-infection, both, supernatants and cells, were collected and the viral genome was assessed by real-time polymerase chain reaction analysis.

Results: Treatments with 1% potassium peroxymonosulfate led to significant reduction in all tested types comparable to disinfecting effects by 0.1% NaClO. Overall, potassium peroxymonosulfate demonstrated sufficient inactivation of the major epidemic keratoconjunctivitis-causing to be considered for disinfection and prevention purposes in ophthalmological clinics and hospitals.

Conclusion: This study demonstrated that potassium peroxymonosulfate is a promising disinfectant for the prevention of epidemic keratoconjunctivitis nosocomial infections in ophthalmological clinics.
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http://dx.doi.org/10.1177/1120672119891408DOI Listing
December 2019

Fowl Adenovirus (FAdV) Recombination with Intertypic Crossovers in Genomes of FAdV-D and FAdV-E, Displaying Hybrid Serological Phenotypes.

Viruses 2019 11 26;11(12). Epub 2019 Nov 26.

Christian Doppler Laboratory for Innovative Poultry Vaccines, University of Veterinary Medicine, 1210 Vienna, Austria.

After analyzing 27 new genomes from fowl adenovirus (FAdV) field isolates and so-far unsequenced prototypes, we report the first evidence for recombination in FAdVs. Recombination was confined to species FAdV-D and FAdV-E, accommodating the largest number of, and the intraspecies-wise most differentiated, types. The majority of detected events occurred in FAdV-E, involving segments with parental origin of all constitutive types. Together with the diversity of breakpoints, this suggests widespread recombination in this species. With possible constraints through species-specific genes and diversification patterns, the recombinogenic potential of FAdVs attains particular interest for inclusion body hepatitis (IBH), an important disease in chickens, caused by types from the recombination-prone species. Autonomously evolving, recombinant segments were associated with major sites under positive selection, among them the capsid protein hexon and fiber genes, the right-terminal ORFs 19, 25, and the ORF20/20A family. The observed mosaicism in genes indicated as targets of adaptive pressures points toward an immune evasion strategy. Intertypic hexon/fiber-recombinants demonstrated hybrid neutralization profiles, retrospectively explaining reported controversies on reference strains B3-A, T8-A, and X11-A. Furthermore, cross-neutralization supported sequence-based evidence for interdomain recombination in fiber and contributed to a tentatively new type. Overall, our findings challenge the purported uniformity of types responsible for IBH, urging more complete identification strategies for FAdVs. Finally, important consequences arise for studies investigating cross-protection against IBH.
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http://dx.doi.org/10.3390/v11121094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950264PMC
November 2019

Epidemic Myalgia Associated with Human Parechovirus Type 3 Infection.

Intern Med 2020 Mar 31;59(5):739-744. Epub 2019 Oct 31.

Department of Internal and Geriatric Medicine, Kita-Harima Medical Center, Japan.

A 42-year-old man was hospitalized due to a fever, orchiodynia, and extremely severe myalgia predominantly in the extremities, which made it difficult for him to stand or walk. He had a history of contact with his son who had acute upper respiratory infection. Based on the characteristic clinical symptoms and detection of the partial sequence of human parechovirus type 3 (HPeV3) in throat swabs as well as stool and serum samples, he was diagnosed with epidemic myalgia associated with HPeV3 infection. Because HPeV3 infection is widespread among children in Japan, HPeV3-associated myalgia should be considered when adult patients manifest such distinguishing clinical characteristics.
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http://dx.doi.org/10.2169/internalmedicine.3326-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086318PMC
March 2020

Enterovirus-Associated Hand-Foot and Mouth Disease and Neurological Complications in Japan and the Rest of the World.

Int J Mol Sci 2019 Oct 20;20(20). Epub 2019 Oct 20.

Division 4, Infectious Disease Surveillance Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.

Enteroviruses (EVs) are responsible for extremely large-scale, periodic epidemics in pediatric cohorts, particularly in East and Southeast Asia. Clinical presentation includes a diverse disease spectrum, including hand-foot and mouth disease (HFMD), aseptic meningitis, encephalitis, acute flaccid paralysis, and acute flaccid myelitis. HFMD is predominantly attributable to EV-A types, including the major pathogen EV-A71, and coxsackieviruses, particularly CV-A6, CV-A16, and CV-A10. There have been multiple EV-A71 outbreaks associated with a profound burden of neurological disease and fatal outcomes in Asia since the early 1980s. Efficacious vaccines against EV-A71 have been developed in China but widespread pediatric vaccination programs have not been introduced in other countries. Encephalitis, as a consequence of complications arising from HFMD infection, leads to damage to the thalamus and medulla oblongata. Studies in Vietnam suggest that myoclonus is a significant indicator of central nervous system (CNS) complications in EV-A71-associated HFMD cases. Rapid response in HFMD cases in children is imperative to prevent the progression to a CNS infection; however, prophylactic and therapeutic agents have not been well established internationally, therefore surveillance and functional studies including development of antivirals and multivalent vaccines is critically important to reduce disease burden in pediatric populations.
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http://dx.doi.org/10.3390/ijms20205201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834195PMC
October 2019

Assessment of clinical signs associated with adenoviral epidemic keratoconjunctivitis cases in southern Japan between 2011 and 2014.

Diagn Microbiol Infect Dis 2019 Dec 7;95(4):114885. Epub 2019 Aug 7.

Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan; Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo, Japan. Electronic address:

Adenoviral epidemic keratoconjunctivitis (EKC) is a major cause of ocular morbidity worldwide and specific antiviral therapies are not available. EKC is primarily caused by Human adenovirus D (HAdV-D) types 8, 37, 53, 54, 56 and 64. Considering the genomic variation in HAdV-D, we hypothesized that clinical signs could be differentiated by virus type. The hypothesis was retrospectively tested with clinical signs recorded from 250 patients with ocular infections visiting an ophthalmological clinic in southern Japan between 2011 and 2014. The results showed that conjunctival opacity, corneal epithelial disorders and pre-auricular lymphadenopathy, were more frequently associated with EKC than other ocular infections. Furthermore, HAdV types 8, 37 and 54, caused corneal complications and longer infections significantly more frequently than infections by types 53 and 56 (P < 0.05). Our descriptive results supported that symptoms severity vary with the infecting type, however, further research is needed to improve diagnosis of EKC.
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http://dx.doi.org/10.1016/j.diagmicrobio.2019.114885DOI Listing
December 2019

[Neuromyelitis optica].

Medicina (B Aires) 2019 ;79 Suppl 3:60-65

Centro Hospitalario Pereira Rossell, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay. E-mail:

Neuromyelitis optica (NMO) is an autoimmune, inflammatory and de myelinat ing disorder of the central nervous system with a predilection for the optic nerves and spinal cord. In 2004 the association of NMO with an antibody against the water channel aquaporin 4 (anti-AQP4) was published as a different pathology from multiple sclerosis (MS). Currently the term NMO spectrum disorders (NMOSD) is proposed, because the manifestations of the disease can be more extensive, affecting in addition to the optic nerve and spinal cord, the area postrema of the dorsal medulla, brainstem, diencephalon and typical brain areas (periependymal, corpus callosum, internal capsule and subcortical white matter). NMOSD is also applied to patients who meet the NMO criteria and are negative for AQP4-IgG. Within the latter group, the presence of another antibody, anti-MOG, has been detected in 20%, with a different physiopathological mechanism, but with a similar clinic and a better prognosis. The immunosuppressive treatment in the attack, as well as the long-term treatment in the cases that are indicated, is fundamental to avoid sequelaes and recurrences. The correct diagnosis of this entity is essential since it can be aggravated with the use of drugs useful in the treatment of MS. In this publication we will review the pathophysiology, clinical and diagnostic criteria of NMOSD, and discuss the different therapeutic options.
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October 2019

PRISEC: Comparison of Symmetric Key Algorithms for IoT Devices.

Sensors (Basel) 2019 Oct 5;19(19). Epub 2019 Oct 5.

Departamento de Informática, Universidade da Beira Interior, 6201-601 Covilhã, Portugal.

With the growing number of heterogeneous resource-constrained devices connected to the Internet, it becomes increasingly challenging to secure the privacy and protection of data. Strong but efficient cryptography solutions must be employed to deal with this problem, along with methods to standardize secure communications between these devices. The PRISEC module of the UbiPri middleware has this goal. In this work, we present the performance of the AES (Advanced Encryption Standard), RC6 (Rivest Cipher 6), Twofish, SPECK128, LEA, and ChaCha20-Poly1305 algorithms in Internet of Things (IoT) devices, measuring their execution times, throughput, and power consumption, with the main goal of determining which symmetric key ciphers are best to be applied in PRISEC. We verify that ChaCha20-Poly1305 is a very good option for resource constrained devices, along with the lightweight block ciphers SPECK128 and LEA.
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http://dx.doi.org/10.3390/s19194312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6806263PMC
October 2019

Genomic characterization of human adenovirus type 4 strains isolated worldwide since 1953 identifies two separable phylogroups evolving at different rates from their most recent common ancestor.

Virology 2019 12 8;538:11-23. Epub 2019 Sep 8.

Infectious Disease Program, Lovelace Respiratory Research Institute, New Mexico, USA. Electronic address:

Species Human mastadenovirus E (HAdV-E) comprises several simian types and a single human type: HAdV-E4, a respiratory and ocular pathogen. RFLP analysis for the characterization of intratypic genetic variability has previously distinguished two HAdV-E4 clusters: prototype (p)-like and a-like. Our analysis of whole genome sequences confirmed two distinct lineages, which we refer to as phylogroups (PGs). PGs I and II comprise the p- and a-like genomes, respectively, and differ significantly in their G + C content (57.7% ± 0.013 vs 56.3% ± 0.015). Sequence differences distinguishing the two clades map to several regions of the genome including E3 and ITR. Bayesian analyses showed that the two phylogroups diverged approximately 602 years before the present. A relatively faster evolutionary rate was identified for PG II. Our data provide a rationale for the incorporation of phylogroup identity to HAdV-E4 strain designation to reflect the identified unique genetic characteristics that distinguish PGs I and II.
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http://dx.doi.org/10.1016/j.virol.2019.08.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448680PMC
December 2019

Quantitative comparison between single-photon emission computed tomography and positron emission tomography imaging of lung ventilation with Tc-technegas and Ga-gallgas in patients with chronic obstructive pulmonary disease: A pilot study.

World J Nucl Med 2019 Jul-Sep;18(3):251-257

Center for Nuclear Medicine, Clinics Hospital, Medicine Faculty, UDELAR, Montevideo, Uruguay.

The aim of this study was quantitative comparison between Ga-Gallgas positron emission tomography (PET) and Tc-Technegas single photon emission computed tomography (SPECT) for lung ventilation function assessment in patients with moderate-to-severe obstructive pulmonary disease and to identify image-derived texture features correlating to the physiologic parameters. Five patients with moderate-to-severe chronic obstructive pulmonary disease with PET and SPECT lung ventilation scans were selected for this study. Threshold-based segmentations were used to compare ventilated regions between both imaging techniques. Histograms of both scans were compared to reveal main differences in distributions of radiotracers. Volumes of segmentation as well as 50 textural features measured in the pulmonary region were correlated to the forced expiratory volume in 1 s (FEV1) as the relevant physiological variable. A better peripheral distribution of the radiotracer was observed in PET scans for three out of five patients. A segmentation threshold of 27% and 31% for normalized scans, for PET and SPECT respectively, was found optimal for volume correlation with FEV1. A high correlation (Pearson correlation coefficient >0.9) was found between 16 texture features measured from SPECT and 7 features measured from PET and FEV1. Quantitative measurements revealed different tracer distribution in both techniques. These results suggest that tracer distribution patterns may depend on the cause of the pulmonary obstruction. We found several texture features measured from SPECT to correlate to FEV1.
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http://dx.doi.org/10.4103/wjnm.WJNM_45_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714146PMC
September 2019

PRISER: Managing Notification in Multiples Devices with Data Privacy Support.

Sensors (Basel) 2019 Jul 13;19(14). Epub 2019 Jul 13.

Department of Computer Engineering, University of Coimbra, 3000-370 Coimbra, Portugal.

With the growing number of mobile devices receiving daily notifications, it is necessary to manage the variety of information produced. New smart devices are developed every day with the ability to generate, send, and display messages about their status, data, and information about other devices. Consequently, the number of notifications received by a user is increasing and their tolerance may decrease in a short time. With this, it is necessary to develop a management system and notification controls. In this context, this work proposes a notification and alert management system called PRISER. Its focus is on user profiles and environments, applying data privacy criteria.
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http://dx.doi.org/10.3390/s19143098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679164PMC
July 2019

Upregulated expression of the antioxidant sestrin 2 identified by transcriptomic analysis of Japanese encephalitis virus-infected SH-SY5Y neuroblastoma cells.

Virus Genes 2019 Oct 10;55(5):630-642. Epub 2019 Jul 10.

Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, N20, W10, Kita-ku, Sapporo, 001-0020, Japan.

Japanese encephalitis virus (JEV) exerts a profound burden of viral encephalitis. We have investigated the differentially expressed transcripts in the neuronal transcriptome during JEV infection by RNA sequencing (RNA-Seq) of virus-infected SH-SY5Y human neuroblastoma cells. Gene ontology analysis revealed significant enrichment from two main pathways: endoplasmic reticulum (ER)-nucleus signaling (P value: 5.75E-18; false discovery rate [FDR] 3.11E-15) and the ER unfolded protein response (P value: 7.58E-18; FDR 3.11E-15). qPCR validation showed significant upregulation and differential expression (P < 0.01) of ER stress-signaling transcripts (SESN2, TRIB3, DDIT3, DDIT4, XBP1, and ATF4) at 24 h post-infection for both low (LN) and high (HN) neurovirulence JEV strains. Immunoblot analysis following JEV infection of SH-SY5Y cells showed an increase in levels of SESN2 protein following JEV infection. Similarly, Zika virus (MR766) infection of SH-SY5Y showed a titer-dependent increase in ER stress-signaling transcripts; however, this was absent or diminished for DDIT4 and ATF4, respectively, suggestive of differences in the induction of stress-response transcripts between flaviviruses. Interestingly, SLC7A11 and SLC3A2 mRNA were also both deregulated in JEV-infected SH-SY5Y cells and encode the two constituent subunits of the plasma membrane xCT amino acid antiporter that relieves oxidative stress by export of glutamate and import of cystine. Infection of SH-SY5Y and HEK293T cells by the JEV HN strain Sw/Mie/40/2004 lead to significant upregulation of the SLC7A11 mRNA to levels comparable to DDIT3. Our findings suggest upregulation of antioxidants including SESN2 and, also, the xCT antiporter occurs to counteract the oxidative stress elicited by JEV infection.
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http://dx.doi.org/10.1007/s11262-019-01683-xDOI Listing
October 2019