Nanoparticle-based vaccine development and evaluation against viral infections in pigs

International audienceAbstractVirus infections possess persistent health challenges in swine industry leading to severe economic losses worldwide. The economic burden caused by virus infections such as Porcine Reproductive and Respiratory Syndrome Virus, Swine influenza virus, Porcine Epidemic Diarrhea Virus, Porcine Circovirus 2, Foot and Mouth Disease Virus and many others are associated with severe morbidity, mortality, loss of production, trade restrictions and investments in control and prevention practices. Pigs can also have a role in zoonotic transmission of some viral infections to humans. Inactivated and modified-live virus vaccines are available against porcine viral infections with variable efficacy under field conditions. Thus, improvements over existing vaccines are necessary to: (1) Increase the breadth of protection against evolving viral strains and subtypes; (2) Control of emerging and re-emerging viruses; (3) Eradicate viruses localized in different geographic areas; and (4) Differentiate infected from vaccinated animals to improve disease control programs. Nanoparticles (NPs) generated from virus-like particles, biodegradable and biocompatible polymers and liposomes offer many advantages as vaccine delivery platform due to their unique physicochemical properties. NPs help in efficient antigen internalization and processing by antigen presenting cells and activate them to elicit innate and adaptive immunity. Some of the NPs-based vaccines could be delivered through both parenteral and mucosal routes to trigger efficient mucosal and systemic immune responses and could be used to target specific immune cells such as mucosal microfold (M) cells and dendritic cells (DCs). In conclusion, NPs-based vaccines can serve as novel candidate vaccines against several porcine viral infections with the potential to enhance the broader protective efficacy under field conditions. This review highlights the recent developments in NPs-based vaccines against porcine viral pathogens and how the NPs-based vaccine delivery system induces innate and adaptive immune responses resulting in varied level of protective efficacy

Tectonic geomorphology and paleoseismology of the Lake Heron and Torlesse faults, mid-Canterbury, New Zealand.

A number of reverse and strike-slip faults are distributed throughout mid-Canterbury, South Island, New Zealand, due to oblique continental collision. There is limited knowledge on fault interaction in the region, despite historical multi-fault earthquakes involving both reverse and strike-slip faults. The surface expression and paleoseismicity of these faults can provide insights into fault interaction and seismic hazards in the region. In this thesis, I studied the Lake Heron and Torlesse faults to better understand the key differences between these two adjacent faults located within different ‘tectonic domains’. Recent activity and surface expression of the Lake Heron fault was mapped and analysed using drone survey, Structure-from-Motion (SfM) derived Digital Surface Model (DSM), aerial image, 5 m-Digital Elevation Model (DEM), luminescence dating technique, and fold modelling. The results show a direct relationship between deformation zone width and the thickness of the gravel deposits in the area. Fold modelling using fault dip, net slip and gravel thickness produces a deformation zone comparable to the field, indicating that the fault geometry is sound and corroborating the results. This result Is consistent with global studies that demonstrate deposit (or soil thickness) correlates to fault deformation zone width, and therefore is important to consider for fault displacement hazard. A geomorphological study on the Torlesse fault was conducted using SfM-DSM, DEM and aerial images Ground Penetrating Radar (GPR) survey, trenching, and radiocarbon and luminescence dating. The results indicate that the Torlesse fault is primarily strike-slip with some dip slip component. In many places, the bedding-parallel Torlesse fault offsets post-glacial deposits, with some evidence of flexural slip faulting due to folding. Absolute dating of offset terraces using radiocarbon dating and slip on fault determined from lateral displacement calculating tool demonstrates the fault has a slip rate of around 0.5 mm/year to 1.0 mm/year. The likelihood of multi-fault rupture in the Torlesse Range has been characterised using paleoseismic trenching, a new structural model, and evaluation of existing paleoseismic data on the Porters Pass fault. Identification of overlapping of paleoseismic events in main Torlesse fault, flexural-slip faults and the Porters Pass fault in the Torlesse Range shows the possibility of distinct or multi-fault rupture on the Torlesse fault. The structural connectivity of the faults in the Torlesse zone forming a ‘flower structure’ supports the potential of multi-fault rupture. Multi-fault rupture modelling carried out in the area shows a high probability of rupture in the Porters Pass fault and Esk fault which also supports the co-rupture probability of faults in the region. This study offers a new understanding of the chronology, slip distribution, rupture characteristics and possible structural and kinematic relationship of Lake Heron fault and Torlesse fault in the South Island, New Zealand

Effects of planting configuration and row spacing on growth and production of potato under mulched condition in Dadeldhura, Nepal

An experiment was conducted at the research site of Dadeldhura, Nepal in 2019 to identify optimum plant spacing for potato under mulched condition. Three levels of inter row spacing; 60 cm with single row per bed (1RB), 45 cm with double row per bed (2RB) and 30 cm with triple row per bed (3RB) and intra row spacing (20, 30 and 40 cm) were laid out in factorial randomized complete block design with three replications. Results showed that there was significant difference (p<0.05) for all parameters except on days to 50% germination, 90% flowering, 50% maturity and on main stem number and graded large sized tuber number and it's weight. Growth parameters namely canopy, leaf number and leaf area were significantly higher (p<0.05) in 60 cm (1RB) ×30 cm spacing. Plant height and leaf area index was significantly higher (p<0.05) in 60 cm (1RB) × 20 cm and 30(3RB) ×20 cm spacing respectively. Total number of tubers m-2 , weight of tubers  m-2, weight of marketable tubers m-2, harvest index, number of small sized tuber m-2 ,weight of small sized tubers m-2 and weight of medium sized tubers m-2 were found to be 56.24%,39.79%, 47.98%,4.41%,90.56%, 113.23% and 70.15% significantly higher (p<0.05)  in 30 cm (3RB) compared to 60 cm on (1RB) inter row spacing respectively and 59.72%, 61.15%, 58.30%, 4.41%, 114.90%, 137.31%, 55.39% higher in 20cm compared to 40 cm intra row spacing. Interaction effect was significant (p<0.05)  in marketable tuber number and medium sized tuber number in which the average highest number of marketable tubers (134.44) and medium sized tubers (121.08) was found in 30(3RB) ×20 cm spacing which was 165.95% and 235.03% significantly higher compared to  60×40 cm spacing respectively. So, this study showed that 30(3RB) ×20 cm spacing would be best spacing combination under mulched condition

Present status and future prospects to safeguard Nepali citrus industry against Chinese citrus fly (Bactrocera minax Enderlein)

Unlike other Tephrid flies, the Chinese citrus fly (Bactrocera minax Enderlein) is univoltine and oligophagous species strictly restricted to citrus fruits. It has been a serious threat to the citrus industry in China, Bhutan, India and Nepal causing up to 100% of fruit drop before the harvest. Citrus groves, especially tight-skinned cultivars, sweet orange (Citrus sinensis L. Osbeck) in mid-hill districts like Ramechhap, Sindhuli, Dolakha, Kavre, Syangja, Gulmi, etc. have been threatened while in some pockets, lemon, acid lime, and mandarin have vanished due to the Chinese citrus fly (CCF). The driver behind the spread of this invasive pest seems to be poor research works on the phenology of the pest, ill-equipped management practices, flying nature of adult fly and easy movement of infested fruits. Therefore, with reviewing published data, this study aimed to figure out the most appropriate management technology for curbing the CCF and make comprehensive material for safeguarding the citrus industry in the future. Since Area-Wide Integrated Pest Management (AW-IPM) or Area-Wide Control Program (AWCP) was found to be an effective tool to control the CCF, individual practices are crucial to incorporate. Monitoring the pest with the lure of protein hydrolase (PH) and subsequently killing adults with attractive protein baits of 25% hydrolyzed protein + insecticide as lethal dinner is mentioned exceptionally better. In AWCP domestic practice: orchard sanitation is not so effective if the orchards are sloppy while shallow tillage adds less to the natural enemy mechanism of CCF pupae in the soil. Equally, we conclude that Sterile Insect Technology (SIT) is not so economical and the boons of natural enemies, parasitoid and entomo-pathogens against CCF, is yet to be exploited

Resource use efficiency of maize production with and without irrigation system in Kaski, Nepal

The study examined the resource use efficiency of maize production in rainfed and irrigated conditions in Kaski, Nepal. It focused specially on the production function of maize, resource use efficiency and socioeconomic characteristics of the farmers. A well-structured interview schedule was used in this study. Out of the 368 households interviewed, 165 farmers cultivated maize and a total of 157 farmers (59 from irrigated and 98 from rainfed) provided useful data. The data analysis was done by using Microsoft excel and SPSS. Cobb-Douglas production function was used to determine the resource use efficiency of maize production.  Compared to rainfed system, maize productivity in irrigated system was higher despite the use of fewer input implying irrigation. Increase in seed use by 10% increased the yield by 1.9% in case of rainfed system and 0.05% in case of the irrigated system. The major implication for the study is that farmers should make proper utilization of their resources to achieve higher level of resource use efficiency

Effect of Low Temperature Baking in Nitrogen on the Performance of a Niobium Superconducting Radio Frequency Cavity

We report the rf performance of a single-cell superconducting radiofrequency cavity after low temperature baking in a nitrogen environment. A significant increase in quality factor has been observed when the cavity was heat treated in the temperature range of 120-160 {\deg}C with a nitrogen partial pressure of ~25 mTorr. This increase in quality factor as well as the Q-rise phenomenon (anti-Q-slope) is similar to those previously obtained with high temperature nitrogen doping as well as titanium doping. In this study, a cavity N2-treated at 120 {\deg}C and at140 {\deg}C, showed no degradation in accelerating gradient, however the accelerating gradient was degraded by 25 with a 160 {\deg}C N2 treatment. Sample coupons treated in the same conditions as the cavity were analyzed by scanning electron microscope, x-ray photoelectron spectroscopy and secondary ion mass spectroscopy revealed a complex surface composition of Nb_2O5, NbO and NbN(1-x)Ox within the rf penetration depth. Furthermore, magnetization measurements showed no significant change on bulk superconducting properties

Nitrogen uptake and economics of black rice (Oryza sativa L. indica) under different crop geometries and nitrogen management practices

Black rice has more antioxidants than any other rice variety.  It is considered to have multiple benefits in human health due to the presence of different antioxidants. A field experiment was conducted during rainy season of 2015-2016 to assess the nitrogen uptake, use efficiency and economics of black rice production under different crop geometry and nitrogen (N) management practices in Rampur, Chitwan, Nepal. The experiment was laid out in strip plot design with three replications. The experiment consisted of  treatment combination of three crop geometry (20 cm × 20 cm, 20 cm × 15 cm and 15 cm × 15 cm) in vertical plots and three nitrogen management practices (N level: 30 kg N ha-1, 60 kg N ha-1, and LCC based N-management) in horizontal plots. The results showed that the highest N uptake was recorded from closer spacing (15 cm × 15 cm) with LCC based N management. The net return and B: C ratios were higher at a closer spacing of 15 cm × 15 cm with LCC based N management and closer spacing of 15 cm × 15 cm with N application of 60 kg ha-1. The overall analysis revealed that LCC based N management under closer crop geometry (15 cm × 15 cm) was the best management practices because of high nitrogen uptake and highest monetary return with B: C ratio of 5.76

Performance of ChatGPT on USMLE: Unlocking the Potential of Large Language Models for AI-Assisted Medical Education

Artificial intelligence is gaining traction in more ways than ever before. The popularity of language models and AI-based businesses has soared since ChatGPT was made available to the general public via OpenAI. It is becoming increasingly common for people to use ChatGPT both professionally and personally. Considering the widespread use of ChatGPT and the reliance people place on it, this study determined how reliable ChatGPT can be for answering complex medical and clinical questions. Harvard University gross anatomy along with the United States Medical Licensing Examination (USMLE) questionnaire were used to accomplish the objective. The paper evaluated the obtained results using a 2-way ANOVA and posthoc analysis. Both showed systematic covariation between format and prompt. Furthermore, the physician adjudicators independently rated the outcome's accuracy, concordance, and insight. As a result of the analysis, ChatGPT-generated answers were found to be more context-oriented and represented a better model for deductive reasoning than regular Google search results. Furthermore, ChatGPT obtained 58.8% on logical questions and 60% on ethical questions. This means that the ChatGPT is approaching the passing range for logical questions and has crossed the threshold for ethical questions. The paper believes ChatGPT and other language learning models can be invaluable tools for e-learners; however, the study suggests that there is still room to improve their accuracy. In order to improve ChatGPT's performance in the future, further research is needed to better understand how it can answer different types of questions.Comment: 12 pages, 4 Figues, 4 table

Mutations in a Highly Conserved Motif of nsp1? Protein Attenuate the Innate Immune Suppression Function of Porcine Reproductive and Respiratory Syndrome Virus

Citation: Li Y, Shyu D-L, Shang P, Bai J, Ouyang K, Dhakal S, Hiremath J, Binjawadagi B, Renukaradhya GJ, Fang Y. 2016. Mutations in a highly conserved motif of nsp1? protein attenuate the innate immune suppression function of porcine reproductive and respiratory syndrome virus. J Virol 90:3584–3599. doi:10.1128/JVI.03069-15.Porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 1? (nsp1?) is a multifunctional viral protein, which is involved in suppressing the host innate immune response and activating a unique ?2/?1 programmed ribosomal frameshifting (PRF) signal for the expression of frameshifting products. In this study, site-directed mutagenesis analysis showed that the R128A or R129A mutation introduced into a highly conserved motif (123GKYLQRRLQ131) reduced the ability of nsp1? to suppress interferon beta (IFN-?) activation and also impaired nsp1?'s function as a PRF transactivator. Three recombinant viruses, vR128A, vR129A, and vRR129AA, carrying single or double mutations in the GKYLQRRLQ motif were characterized. In comparison to the wild-type (WT) virus, vR128A and vR129A showed slightly reduced growth abilities, while the vRR129AA mutant had a significantly reduced growth ability in infected cells. Consistent with the attenuated growth phenotype in vitro, pigs infected with nsp1? mutants had lower levels of viremia than did WT virus-infected pigs. Compared to the WT virus in infected cells, all three mutated viruses stimulated high levels of IFN-? expression and exhibited a reduced ability to suppress the mRNA expression of selected interferon-stimulated genes (ISGs). In pigs infected with nsp1? mutants, IFN-? production was increased in the lungs at early time points postinfection, which was correlated with increased innate NK cell function. Furthermore, the augmented innate response was consistent with the increased production of IFN-? in pigs infected with mutated viruses. These data demonstrate that residues R128 and R129 are critical for nsp1? function and that modifying these key residues in the GKYLQRRLQ motif attenuates virus growth ability and improves the innate and adaptive immune responses in infected animals

Regional variation in pig farmer awareness and actions regarding Japanese encephalitis in Nepal : implications for public health education

The objective was to explore regional variations in farmer awareness and actions towards Japanese Encephalitis (JE) in Nepal; the association of awareness and actions with farm and farmer variables; and the implications for public health education and extension services. Social factors such as literacy, gender, and cultural practices were associated with farmer attitudes, knowledge and practices for JE control. The low uptake of vaccine and lack of infrastructure or financial capacity to house pigs adequately suggest that farmer personal protection should be a priority for education. JE is a mosquito-borne zoonotic disease with pigs as the amplifying hosts