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1.
Vet Microbiol ; 289: 109958, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38181600

ABSTRACT

Neonatal mortality has been increasingly reported on swine breeding farms experiencing swine idiopathic vesicular disease (SIVD) outbreaks, which can be accompanied by lethargy, diarrhea, and neurologic signs in neonates. Seneca Valley Virus (SVV), or Senecavirus A, has been detected in clinical samples taken from pigs with SIVD. Experimental SVV inoculation has caused vesicular disease in pigs, particularly during the stages from weaning to finishing. However, it remains crucial to investigate whether SVV directly contributes to the increase in neonatal mortality rates. The following study was conducted to chronicle the pathogenesis of SVV infection in sows and their offspring. Ten sows were intranasally inoculated with 4.75 × 107 plaque-forming units of the virus per sow either late in gestation (n = 5) or within fourteen days of farrowing (n = 5). Each sow replicated SVV following intranasal inoculation, but only one out of ten sows developed a vesicular lesion on the snout. Evidence of transplacental infection was observed in two litters, and an additional two litters became infected following parturition out of five litters from sows inoculated in late gestation. No clinical signs were observed in the infected neonates. Likewise, no clinical signs were observed in the other five litters inoculated after farrowing, although each piglet did replicate the challenge virus. In this study, the experimental challenge of SVV did not result in neonatal mortality in contrast to observations in the field; however, it has shed light on the pathogenesis of the virus, the transmission of SVV between sows and their offspring, and host immune response that can help shape control measures in the field.


Subject(s)
Picornaviridae Infections , Picornaviridae , Swine Diseases , Swine , Animals , Female , Pregnancy , Picornaviridae Infections/veterinary , Disease Outbreaks/veterinary
2.
Pathogens ; 12(12)2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38133308

ABSTRACT

The present study evaluated the potential utility of feather samples for the convenient and accurate detection of avian influenza virus (AIV) in commercial poultry. Feather samples were obtained from AIV-negative commercial layer facilities in Iowa, USA. The feathers were spiked with various concentrations (106 to 100) of a low pathogenic strain of H5N2 AIV using a nebulizing device and were evaluated for the detection of viral RNA using a real-time RT-PCR assay immediately or after incubation at -20, 4, 22, or 37 °C for 24, 48, or 72 h. Likewise, cell culture medium samples with and without the virus were prepared and used for comparison. In the spiked feathers, the PCR reliably (i.e., 100% probability of detection) detected AIV RNA in eluates from samples sprayed with 103 EID50/mL or more of the virus. Based on half-life estimates, the feathers performed better than the corresponding media samples (p < 0.05), particularly when the samples were stored at 22 or 37 °C. In conclusion, feather samples can be routinely collected from a poultry barn as a non-invasive alternative to blood or oropharyngeal-cloacal swab samples for monitoring AIV.

3.
Sci Rep ; 13(1): 1711, 2023 01 31.
Article in English | MEDLINE | ID: mdl-36720913

ABSTRACT

We have previously shown that neoadjuvant chemotherapy can induce the degradation of tumour ribosomal RNA (rRNA) in patients with advanced breast cancer, a phenomenon we termed "RNA disruption". Extensive tumour RNA disruption during chemotherapy was associated with a post-treatment pathological complete response and improved disease-free survival. The RNA disruption assay (RDA), which quantifies this phenomenon, is now being evaluated for its clinical utility in a large multinational clinical trial. However, it remains unclear if RNA disruption (i) is manifested across many tumour and non-tumour cell types, (ii) can occur in response to cell stress, and (iii) is associated with tumour cell death. In this study, we show that RNA disruption is induced by several mechanistically distinct chemotherapy agents and report that this phenomenon is observed in response to oxidative stress, endoplasmic reticulum (ER) stress, protein translation inhibition and nutrient/growth factor limitation. We further show that RNA disruption is dose- and time-dependent, and occurs in both tumourigenic and non-tumourigenic cell types. Northern blotting experiments suggest that the rRNA fragments generated during RNA disruption stem (at least in part) from the 28S rRNA. Moreover, we demonstrate that RNA disruption is reproducibly associated with three robust biomarkers of cell death: strongly reduced cell numbers, lost cell replicative capacity, and the generation of cells with a subG1 DNA content. Thus, our findings indicate that RNA disruption is a widespread phenomenon exhibited in mammalian cells under stress, and that high RNA disruption is associated with the onset of cell death.


Subject(s)
RNA, Ribosomal , RNA , Animals , Humans , RNA, Ribosomal/genetics , RNA, Neoplasm , Ribosomes , Cell Death/genetics , Mammals
4.
J Virol Methods ; 308: 114594, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35931229

ABSTRACT

The surveillance of migratory wild birds (MWBs) for avian influenza virus (AIV) allows detecting the emergence of highly pathogenic AIV that can infect domestic poultry and mammals, new subtypes, and antigenic/genetic variants. The current AIV surveillance system for MWBs in the United States is based on virus isolation (VI) followed by sequencing isolates. This system primarily focuses on the early detection of H5 and H7 AIVs. However, it is suboptimal in assessing diverse AIV subtypes at any given time because of the low VI success rate. To improve such a shortfall, a SYBR® Green-based real-time reverse transcription-polymerase chain reaction (rtRT-PCR) panel was developed for direct HA subtyping of AIVs in oropharyngeal-cloacal (OPC) swabs from MWBs. Under optimal conditions, the PCR panel detected AIVs of all 16 different HA subtypes with an average limit of detection of 102.6 copies/reaction (2 µl of extract). In testing 90 OPC swabs from 13 MWB species, the PCR provided a significantly faster turnaround of results and demonstrated the presence of more subtypes and concurrent infection among MWBs compared to what the current surveillance testing algorithm showed. In conclusion, newly developed SYBR® Green rtRT-PCR panel can be a useful tool for monitoring MWBs for AIVs.


Subject(s)
Influenza A virus , Influenza in Birds , Animals , Animals, Wild , Hemagglutinins , Mammals , Real-Time Polymerase Chain Reaction/methods
5.
Pathogens ; 11(7)2022 Jul 02.
Article in English | MEDLINE | ID: mdl-35890004

ABSTRACT

The present study was conducted to assess the potential vector role of feedstuffs for the area spreading of avian influenza virus (AIV). Firstly, feed samples were collected from commercial poultry facilities that experienced highly pathogenic avian influenza (H5N2) in 2014−2015 for AIV testing by a real-time RT−PCR specific for the viral matrix gene. Secondly, feed materials obtained from an AIV-negative farm were spiked with various concentrations of a low pathogenic AIV H5N2. Virus-spiked cell culture media were prepared in the same manner and used for comparison. The spiked feed and media samples were tested by a multiplex real-time RT−PCR ran in a quantitative manner, either immediately or after incubation at −20, 4, 22, and 37 °C for 24, 48, and 72 h. Some of the feedstuffs collected from the poultry facilities or feed mills were positive for AIV RNA but negative by the virus isolation (VI) test, while all the formaldehyde-treated feedstuffs were PCR-negative. In the spiked feeds, the AIV titer was 1−3 logs lower than that in the corresponding media, even when tested immediately after spiking, suggesting that feed might have a negative impact on the virus or PCR detection. The half-life of AIV RNA was shorter at a higher temperature. A significant decay in the viral RNA over time was noted at 37 °C (p < 0.05), suggesting that feedstuffs should be maintained in the cold chain when testing is desired. Furthermore, the thermal degradation of AIV suggests that the heat treatment of feeds could be an alternative to chemical treatment when contamination is suspected. Collectively, the study observations indicate that AIV survivability in feed is relatively low, thus rendering it a low risk.

6.
Animals (Basel) ; 11(9)2021 Sep 10.
Article in English | MEDLINE | ID: mdl-34573631

ABSTRACT

Precision swine production can benefit from autonomous, noninvasive, and affordable devices that conduct frequent checks on the well-being status of pigs. Here, we present a remote monitoring tool for the objective measurement of some behavioral indicators that may help in assessing the health and welfare status-namely, posture, gait, vocalization, and external temperature. The multiparameter electronic sensor board is characterized by laboratory measurements and by animal tests. Relevant behavioral health indicators are discussed for implementing machine learning algorithms and decision support tools to detect animal lameness, lethargy, pain, injury, and distress. The roadmap for technology adoption is also discussed, along with challenges and the path forward. The presented technology can potentially lead to efficient management of farm animals, targeted focus on sick animals, medical cost savings, and less use of antibiotics.

7.
FASEB J ; 35(5): e21511, 2021 05.
Article in English | MEDLINE | ID: mdl-33826201

ABSTRACT

Hydrogen sulfide (H2 S) can be endogenously produced and belongs to the class of signaling molecules known as gasotransmitters. Cystathionine gamma-lyase (CSE)-derived H2 S is implicated in the regulation of cell differentiation and the aging process, but the involvements of the CSE/H2 S system in myogenesis upon aging and injury have not been explored. In this study, we demonstrated that CSE acts as a major H2 S-generating enzyme in skeletal muscles and is significantly down-regulated in aged skeletal muscles in mice. CSE deficiency exacerbated the age-dependent sarcopenia and cardiotoxin-induced injury/regeneration in mouse skeletal muscle, possibly attributed to inefficient myogenesis. In contrast, supplement of NaHS (an H2 S donor) induced the expressions of myogenic genes and promoted muscle regeneration in mice. In vitro, incubation of myoblast cells (C2C12) with H2 S promoted myogenesis, as evidenced by the inhibition of cell cycle progression and migration, altered expressions of myogenic markers, elongation of myoblasts, and formation of multinucleated myotubes. Myogenesis was also found to upregulate CSE expression, while blockage of CSE/H2 S signaling resulted in a suppression of myogenesis. Mechanically, H2 S significantly induced the heterodimer formation between MEF2c and MRF4 and promoted the binding of MEF2c/MRF4 to myogenin promoter. MEF2c was S-sulfhydrated at both cysteine 361 and 420 in the C-terminal transactivation domain, and blockage of MEF2c S-sulfhydration abolished the stimulatory role of H2 S on MEF2c/MRF4 heterodimer formation. These findings support an essential role for H2 S in maintaining myogenesis, presenting it as a potential candidate for the prevention of age-related sarcopenia and treatment of muscle injury.


Subject(s)
Aging/pathology , Cell Differentiation , Cystathionine gamma-Lyase/metabolism , Hydrogen Sulfide/metabolism , Muscle Development , Muscle, Skeletal/cytology , Myoblasts/cytology , Sarcopenia/prevention & control , Animals , Cystathionine gamma-Lyase/genetics , Male , Mice , Muscle, Skeletal/injuries , Muscle, Skeletal/metabolism , Myoblasts/metabolism , Sarcopenia/etiology , Sarcopenia/metabolism , Sarcopenia/pathology
8.
Vet Microbiol ; 253: 108946, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33341466

ABSTRACT

Senecavirus A (SVA) was discovered as a cell culture contaminant in 2002, and multiple attempts to experimentally reproduce disease were unsuccessful. Field reports of porcine idiopathic vesicular disease (PIVD) cases testing PCR positive for SVA in addition to outbreaks of PIVD in Brazil and the United States in 2015 suggested SVA was a causative agent, which has now been consistently demonstrated experimentally. Ease of experimental reproduction of disease with contemporary strains of SVA raised questions concerning the difficulty of reproducing vesicular disease with historical isolates. The following study was conducted to compare the pathogenicity of SVA between historical and contemporary isolates in growing pigs. Six groups of pigs (n = 8) were intranasally inoculated with the following SVA isolates: SVV001/2002, CAN/2011, HI/2012, IA/2015, NC/2015, SD/2015. All isolates induced vesicular disease in at least half of the inoculated pigs from each group. All pigs replicated virus as demonstrated by serum and/or swab samples positive for SVA by quantitative PCR. Pig sera tested by virus neutralization assay demonstrated cross-neutralizing antibodies against all viruses utilized in the study. Cross-neutralizing antibodies from pigs inoculated with historical isolates were lower than those pigs that were inoculated with contemporary isolates. Phylogenetic analysis revealed two clades with SVV001/2002 being in a separate clade compared to the other five isolates. Although differences in the infection kinetics and sequences of these six isolates were found, clinical presentation of vesicular disease was similar between both historical and contemporary isolates.


Subject(s)
Antibodies, Neutralizing/blood , Picornaviridae Infections/veterinary , Picornaviridae/genetics , Picornaviridae/isolation & purification , Swine Diseases/virology , Animals , Antibodies, Viral/blood , Brazil/epidemiology , Cell Line , Disease Outbreaks , Genome, Viral , History, 20th Century , History, 21st Century , Male , Phylogeny , Picornaviridae/classification , Picornaviridae/pathogenicity , Picornaviridae Infections/epidemiology , Picornaviridae Infections/history , Swine , Swine Diseases/epidemiology , Swine Diseases/history , United States/epidemiology
9.
Sci Rep ; 10(1): 8671, 2020 05 26.
Article in English | MEDLINE | ID: mdl-32457334

ABSTRACT

Conventional drug sensitivity assays used to screen prospective anti-cancer agents for cytotoxicity monitor biological processes associated with active growth and proliferation, used as proxies of cell viability. However, these assays are unable to distinguish between growth-arrested (but otherwise viable) cells and non-viable/dead cells. As a result, compounds selected based on the results of these assays may only be cytostatic, halting or slowing tumour progression temporarily, without tumour eradication. Because agents capable of killing tumour cells (cytotoxic drugs) are likely the most promising in the clinic, there is a need for drug sensitivity assays that reliably identify cytotoxic compounds that induce cell death. We recently developed a drug sensitivity assay, called the RNA disruption assay (RDA), which measures a phenomenon associated with tumour cell death. In this study, we sought to compare our assay's performance to that of current commonly used drug sensitivity assays (i.e, the clonogenic, the cell counting kit-8 and the Trypan blue exclusion assays). We found that RNA disruption occurred almost exclusively when total cell numbers decreased (cytotoxic concentrations), with little to no signal detected until cells had lost viability. In contrast, conventional assays detected a decrease in their respective drug sensitivity parameters despite cells retaining their viability, as assessed using a recovery assay. We also found that the RDA can differentiate between drug-sensitive and -resistant cells, and that it can identify agents capable of circumventing drug resistance. Taken together, our study suggests that the RDA is a superior drug discovery tool, providing a unique assessment of cell death.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Discovery/methods , Drug Screening Assays, Antitumor/methods , Ovarian Neoplasms/drug therapy , RNA/analysis , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Doxorubicin/pharmacology , Drug Resistance, Neoplasm/genetics , Female , Humans , Ovarian Neoplasms/genetics , Prospective Studies
10.
J Vet Diagn Invest ; 32(3): 369-381, 2020 May.
Article in English | MEDLINE | ID: mdl-32306863

ABSTRACT

Microcystis is a widespread freshwater cyanobacterium that can produce microcystin, a potent hepatotoxin harmful to animals and humans. Therefore, it is crucial to monitor for the presence of toxigenic Microcystis spp. to provide early warning of potential microcystin contamination. Microscopy, which has been used traditionally to identify Microcystis spp., cannot differentiate toxigenic from non-toxigenic Microcystis. We developed a PCR-based method to detect toxigenic Microcystis spp. based on detection of the microcystin synthetase C (mcyC) gene and 16S rRNA gene. Specificity was validated against toxic and nontoxic M. aeruginosa strains, as well as 4 intergeneric freshwater cyanobacterial strains. Analytical sensitivity was as low as 747 fg/µL genomic DNA (or 3 cells/µL) for toxic M. aeruginosa. Furthermore, we tested 60 water samples from 4 farm ponds providing drinking water to swine facilities in the midwestern United States using this method. Although all water samples were positive for Microcystis spp. (i.e., 16S rRNA gene), toxigenic Microcystis spp. were detected in only 34 samples (57%). Seventeen water samples contained microcystin (0.1-9.1 µg/L) determined with liquid chromatography-mass spectrometry, of which 14 samples (82%) were positive for mcyC. A significant correlation was found between the presence of toxigenic Microcystis spp. and microcystin in water samples (p = 0.0004). Our PCR method can be a low-cost molecular tool for rapid and specific identification of toxigenic Microcystis spp. in farm ponds, improving detection of microcystin contamination, and ensuring water safety for farm animals.


Subject(s)
Microcystins/isolation & purification , Microcystis/isolation & purification , Polymerase Chain Reaction/veterinary , Ponds/microbiology , Bacterial Proteins/analysis , Bacterial Toxins/analysis , Eutrophication , Farms , Midwestern United States , Polymerase Chain Reaction/methods , RNA, Bacterial/analysis , RNA, Ribosomal, 16S/analysis
11.
BMC Vet Res ; 15(1): 453, 2019 Dec 16.
Article in English | MEDLINE | ID: mdl-31842875

ABSTRACT

BACKGROUND: Assessment of the efficacy of a multi-agent chemotherapy protocol in which cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) are administered in canine lymphoma is generally performed by physical measurement of lymph node diameter. However, no consistent correlation has been made with prognostic indicators and the length or absence of clinical remission based on lymph node size. RNA disruption measured mid-therapy has been correlated with increased disease-free survival in recent studies of human cancer and was assessed in this study of canine lymphoma patients. Fine needle aspirate samples were taken before treatment and at weeks 3, 6, and 11 of CHOP therapy. RNA was isolated from these samples and assessed using an Agilent Bioanalyzer. RNA disruption assay (RDA) analysis was performed on the data from the resulting electropherograms. RESULTS: An increased RNA disruption index (RDI) score was significantly associated with improved progression-free survival. CONCLUSIONS: Predicting the risk of early relapse during chemotherapy could benefit veterinary patients by reducing ineffective treatment and could allow veterinary oncologists to switch earlier to a more effective drug regimen.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dog Diseases/drug therapy , Lymphoma, Non-Hodgkin/veterinary , RNA, Neoplasm/analysis , Animals , Cyclophosphamide/therapeutic use , Dogs , Doxorubicin/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Prednisone/therapeutic use , Progression-Free Survival , Vincristine/therapeutic use
12.
Opt Express ; 27(19): 27168-27182, 2019 Sep 16.
Article in English | MEDLINE | ID: mdl-31674583

ABSTRACT

The principle of superposition is a key ingredient for quantum mechanics. A recent work [Phys. Rev. Lett.116, 110403 (2016)10.1103/PhysRevLett.116.110403] has shown that a quantum adder that deterministically generates a superposition of two unknown states is forbidden. Here we consider the implementation of the probabilistic quantum adder in the 3D cavity-transmon system. Our implementation is based on a three-level superconducting transmon qubit dispersively coupled to two cavities. Numerical simulations show that high-fidelity generation of the superposition of two coherent states is feasible with current circuit QED technology. Our method also works for other physical systems such as two optical cavities coupled to a three-level atom or two nitrogen-vacancy center ensembles interacted with one three-level superconducting flux qubit.

13.
Sensors (Basel) ; 19(14)2019 Jul 11.
Article in English | MEDLINE | ID: mdl-31336814

ABSTRACT

Foreign object intrusion is a great threat to high-speed railway safety operations. Accurate foreign object intrusion detection is particularly important. As a result of the lack of intruding foreign object samples during the operational period, artificially generated ones will greatly benefit the development of the detection methods. In this paper, we propose a novel method to generate railway intruding object images based on an improved conditional deep convolutional generative adversarial network (C-DCGAN). It consists of a generator and multi-scale discriminators. Loss function is also improved so as to generate samples with a high quality and authenticity. The generator is extracted in order to generate foreign object images from input semantic labels. We synthesize the generated objects to the railway scene. To make the generated objects more similar to real objects, on scale in different positions of a railway scene, a scale estimation algorithm based on the gauge constant is proposed. The experimental results on the railway intruding object dataset show that the proposed C-DCGAN model outperforms several state-of-the-art methods and achieves a higher quality (the pixel-wise accuracy, mean intersection-over-union (mIoU), and mean average precision (mAP) are 80.46%, 0.65, and 0.69, respectively) and diversity (the Fréchet-Inception Distance (FID) score is 26.87) of generated samples. The mIoU of the real-generated pedestrian pairs reaches 0.85, and indicates a higher scale of accuracy for the generated intruding objects in the railway scene.

14.
Sensors (Basel) ; 19(11)2019 Jun 06.
Article in English | MEDLINE | ID: mdl-31174417

ABSTRACT

Video surveillance-based intrusion detection has been widely used in modern railway systems. Objects inside the alarm region, or the track area, can be detected by image processing algorithms. With the increasing number of surveillance cameras, manual labeling of alarm regions for each camera has become time-consuming and is sometimes not feasible at all, especially for pan-tilt-zoom (PTZ) cameras which may change their monitoring area at any time. To automatically label the track area for all cameras, video surveillance system requires an accurate track segmentation algorithm with small memory footprint and short inference delay. In this paper, we propose an adaptive segmentation algorithm to delineate the boundary of the track area with very light computation burden. The proposed algorithm includes three steps. Firstly, the image is segmented into fragmented regions. To reduce the redundant calculation in the evaluation of the boundary weight for generating the fragmented regions, an optimal set of Gaussian kernels with adaptive directions for each specific scene is calculated using Hough transformation. Secondly, the fragmented regions are combined into local areas by using a new clustering rule, based on the region's boundary weight and size. Finally, a classification network is used to recognize the track area among all local areas. To achieve a fast and accurate classification, a simplified CNN network is designed by using pre-trained convolution kernels and a loss function that can enhance the diversity of the feature maps. Experimental results show that the proposed method finds an effective balance between the segmentation precision, calculation time, and hardware cost of the system.

15.
Vet Microbiol ; 231: 7-10, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30955826

ABSTRACT

Seneca Valley virus (SVV) is a picornavirus that causes vesicular disease in swine. Since it is clinically indistinguishable from vesicular disease caused by food-and-mouth disease virus (FMDV), investigations must be performed to rule out this high consequence pathogen. A large portion of these investigations have involved market-weight swine at slaughter plants. The objective of this study was to describe acute infection dynamics of market-weight gilts (8 months of age) experimentally infected with SVV. At 0 days post inoculation (dpi) all gilts (n=15) were given an intranasal SVV inoculation. Vesicular lesions on the coronary band were first observed on one or more feet by 2 dpi in 4 of the 15 gilts and in all by 5 dpi. Vesicles on the snout were observed in 6 of the 15 gilts beginning at 4 dpi. All gilts became viremic post challenge for about 7 days and developed anti-SVV neutralizing antibodies by 7 dpi. Most vesicular lesions were resolved by 14 dpi. Understanding the pathogenesis of SVV is critical in order to inform decisions that veterinarians and producers must make at the farm level to control this disease.


Subject(s)
Antibodies, Viral/blood , Picornaviridae Infections/veterinary , Picornaviridae , Swine Diseases/virology , Abattoirs , Acute Disease , Animals , Antibodies, Neutralizing/blood , Body Weight , Female , Picornaviridae Infections/pathology , Polymerase Chain Reaction , Sus scrofa , Swine , Swine Diseases/pathology , Viremia/pathology
16.
Phys Rev E ; 99(3-1): 032112, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30999448

ABSTRACT

Quantum thermal devices which can manage heat as their electronic analogs for the electronic currents have attracted increasing attention. Here a three-terminal quantum thermal device is designed by three coupling qubits interacting with three heat baths with different temperatures. Based on the steady-state behavior solved from the dynamics of this system, it is demonstrated that such a device integrates multiple interesting thermodynamic functions. It can serve as a heat current transistor to use the weak heat current at one terminal to effectively amplify the currents through the other two terminals, to continuously modulate them ranging in a large amplitude, and even to switch on or off the heat currents. It is also found that the three currents are not sensitive to the fluctuation of the temperature at the low-temperature terminal, so it can behave as a thermal stabilizer. In addition, we can utilize one terminal temperature to ideally turn off the heat current at any one terminal and to allow the heat currents through the other two terminals, so it can be used as a thermal valve. Finally, we illustrate that this thermal device can control the heat currents to flow unidirectionally, so it has the function of a thermal rectifier.

17.
Biomater Sci ; 7(3): 809-821, 2019 Feb 26.
Article in English | MEDLINE | ID: mdl-30663733

ABSTRACT

Immunosenescence poses a formidable challenge in designing effective influenza vaccines for aging populations. While approved vaccines against influenza viruses exist, their efficacy in older adults is significantly decreased due to the diminished capabilities of innate and adaptive immune responses. In this work, the ability of a combination nanovaccine containing both recombinant hemagglutinin and nucleoprotein to provide protection against seasonal influenza virus infection was examined in young and aged mice. Vaccine formulations combining two nanoadjuvants, polyanhydride nanoparticles and pentablock copolymer micelles, were shown to enhance protection against challenge compared to each adjuvant alone in young mice. Nanoparticles were shown to enhance in vitro activation of dendritic cells isolated from aged mice, while both nanoadjuvants did not induce proinflammatory cytokine secretion which may be detrimental in aged individuals. In addition, the combination nanovaccine platform was shown to induce demonstrable antibody titers in both young and aged mice that correlated with the maintenance of body weight post-challenge. Collectively, these data demonstrate that the combination nanovaccine platform is a promising technology for influenza vaccines for older adults.


Subject(s)
Aging , Influenza Vaccines/immunology , Nanoparticles/chemistry , Orthomyxoviridae Infections/prevention & control , Adjuvants, Immunologic/chemistry , Animals , Antibodies, Viral/blood , Antibodies, Viral/immunology , Dendritic Cells/cytology , Dendritic Cells/immunology , Dendritic Cells/metabolism , Female , Influenza A virus/pathogenicity , Influenza Vaccines/chemistry , Lung/virology , Mice , Mice, Inbred BALB C , Micelles , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/mortality , Polyanhydrides/chemistry , Polymers/chemistry , Survival Rate
18.
BMC Vet Res ; 14(1): 352, 2018 Nov 20.
Article in English | MEDLINE | ID: mdl-30453952

ABSTRACT

BACKGROUND: Senecavirus A, commonly known as Seneca Valley virus (SVV), is a picornavirus that has been infrequently associated with porcine idiopathic vesicular disease (PIVD). In late 2014 there were multiple PIVD outbreaks in several states in Brazil and samples from those cases tested positive for SVV. Beginning in July of 2015, multiple cases of PIVD were reported in the United States in which a genetically similar SVV was also detected. These events suggested SVV could induce vesicular disease, which was recently demonstrated with contemporary US isolates that produced mild disease in pigs. It was hypothesized that stressful conditions may exacerbate the expression of clinical disease and the following experiment was performed. Two groups of 9-week-old pigs were given an intranasal SVV challenge with one group receiving an immunosuppressive dose of dexamethasone prior to challenge. After challenge animals were observed for the development of clinical signs and serum and swabs were collected to study viral shedding and antibody production. In addition, pigs were euthanized 2, 4, 6, 8, and 12 days post inoculation (dpi) to demonstrate tissue distribution of virus during acute infection. RESULTS: Vesicular disease was experimentally induced in both groups with the duration and magnitude of clinical signs similar between groups. During acute infection [0-14 days post infection (dpi)], SVV was detected by PCR in serum, nasal swabs, rectal swabs, various tissues, and in swabs from ruptured vesicles. From 15 to 30 dpi, virus was less consistently detected in nasal and rectal swabs, and absent from most serum samples. Virus neutralizing antibody was detected by 5 dpi and lasted until the end of the study. CONCLUSION: Treatment with an immunosuppressive dose of dexamethasone did not drastically alter the clinical disease course of SVV in experimentally infected nursery aged swine. A greater understanding of SVV pathogenesis and factors that could exacerbate disease can help the swine industry with control and prevention strategies directed against this virus.


Subject(s)
Dexamethasone/pharmacology , Immunosuppressive Agents/pharmacology , Picornaviridae Infections/veterinary , Picornaviridae , Swine Diseases/virology , Animals , Animals, Newborn , Antibodies, Viral/blood , Swine , Swine Vesicular Disease/virology , Virus Shedding/drug effects
19.
Life Sci ; 213: 116-125, 2018 Nov 15.
Article in English | MEDLINE | ID: mdl-30343125

ABSTRACT

AIMS: Hydrogen sulfide (H2S), an important gasotransmitter, is involved in a variety of cellular functions and pathophysiologic processes. Drug resistance due to alterations in drug trafficking and metabolism severely limits the effectiveness of cancer therapy. This study examined the role of H2S in drug resistance in liver cancer cells. MATERIALS AND METHODS: Human primary hepatocellular carcinoma cell line (HepG2) and doxorubicin (Dox)-resistant cells were used in this study. Cell survival was analyzed by MTT, Annexin V-FITC/propidium iodide staining and clonogenic assay. Western blotting was used for analysis of protein expression, and immunoprecipitation was used to determine interactions of LXR/RXR. KEY FINDINGS: The expression of H2S-generating enzyme cystathionine gamma-lyase (CSE) was inhibited by doxorubicin treatment in HepG2 cells, and H2S sensitized Dox-inhibited cell survival and colony formation. In addition, H2S promoted cellular retention of Dox by suppressing the expressions of ABCA1 and ABCG8. H2S significantly blocked Dox-induced heterodimer formation between LXRα and RXRß and attenuated the binding of LXRα/RXRß to the promoters of ABCA1 and ABCG8 genes. RXRß but not LXRα was S-sulfhydrated by H2S, and blockage of RXRß S-sulfhydration abolished the inhibitory role of H2S on LXRα/RXRß heterodimer formation. CSE expression was reduced in Dox-resistant cells in comparison with their parental cells, while H2S could reverse drug resistance in Dox-resistant cells. SIGNIFICANCE: Our study provides a novel solution for reversing drug resistance in cancer cells by targeting H2S signalling.


Subject(s)
Hydrogen Sulfide/metabolism , Hydrogen Sulfide/pharmacology , ATP Binding Cassette Transporter 1/drug effects , ATP Binding Cassette Transporter, Subfamily G, Member 8/drug effects , Carcinoma, Hepatocellular/drug therapy , Cell Death/drug effects , Cell Movement/drug effects , Cell Survival/drug effects , Cystathionine gamma-Lyase/drug effects , Doxorubicin/metabolism , Drug Resistance, Neoplasm/physiology , Hep G2 Cells , Humans , Liver Neoplasms/drug therapy , Retinoid X Receptors/drug effects , Signal Transduction/drug effects
20.
Phys Rev E ; 98(2-1): 022118, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30253594

ABSTRACT

A quantum thermal transistor is designed by the strong coupling between one qubit and one qutrit which are in contact with three heat baths with different temperatures. The thermal behavior is analyzed based on the master equation by both the numerical and the approximately analytic methods. It is shown that the thermal transistor, as a three-terminal device, allows a weak modulation heat current (at the modulation terminal) to switch on and off and effectively modulate the heat current between the other two terminals. In particular, the weak modulation heat current can induce the strong heat current between the other two terminals with the multiple-region amplification of heat current. Furthermore, the heat currents are quite robust to the temperature (current) fluctuation at the lower-temperature terminal within a certain range of temperature, and so it can behave as a heat current stabilizer.

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