scholarly journals Screening of viral-vectored P. falciparum pre-erythrocytic candidate vaccine antigens using chimeric rodent parasites

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254498
Author(s):  
Surendra Kumar Kolli ◽  
Ahmed M. Salman ◽  
Jai Ramesar ◽  
Severine Chevalley-Maurel ◽  
Hans Kroeze ◽  
...  

To screen for additional vaccine candidate antigens of Plasmodium pre-erythrocytic stages, fourteen P. falciparum proteins were selected based on expression in sporozoites or their role in establishment of hepatocyte infection. For preclinical evaluation of immunogenicity of these proteins in mice, chimeric P. berghei sporozoites were created that express the P. falciparum proteins in sporozoites as an additional copy gene under control of the uis4 gene promoter. All fourteen chimeric parasites produced sporozoites but sporozoites of eight lines failed to establish a liver infection, indicating a negative impact of these P. falciparum proteins on sporozoite infectivity. Immunogenicity of the other six proteins (SPELD, ETRAMP10.3, SIAP2, SPATR, HT, RPL3) was analyzed by immunization of inbred BALB/c and outbred CD-1 mice with viral-vectored (ChAd63 or ChAdOx1, MVA) vaccines, followed by challenge with chimeric sporozoites. Protective immunogenicity was determined by analyzing parasite liver load and prepatent period of blood stage infection after challenge. Of the six proteins only SPELD immunized mice showed partial protection. We discuss both the low protective immunogenicity of these proteins in the chimeric rodent malaria challenge model and the negative effect on P. berghei sporozoite infectivity of several P. falciparum proteins expressed in the chimeric sporozoites.

2020 ◽  
Vol 25 (4) ◽  
pp. 287-294
Author(s):  
S. I. Kutukova ◽  
N. P. Beliak ◽  
G. A. Raskin ◽  
M. S. Mukhina ◽  
Yu. V. Ivaskova ◽  
...  

Relevance. Prognostic value of PD-L1 expression in oral cavity squamous cell carcinoma (OCSCC) and its effect on survival is still controversial. It should be to determine the prognostic role of PD-L1 expression on tumor and immune cells of OCSCC and assess their effect on overall survival (OS) and progression-free survival (PFS).Materials and methods. A prospective study included 145 patients, first diagnosed with OCSCC. PD-L1 expression on tumor and immune cells, infiltrating tumor and its microenvironment, was assessed in all tumor samples by IHC, CPS was calculated. Cut-off values were determined by ROC analysis for identification of PD-L1 expression effect on OS and PFS.Results. Most patients with oral mucosa squamous cell carcinoma showed positive expression of PD-L1 on tumor (77.2%) and immune cells (92.4%). The median PD-L1 expression on tumor cells was 13.5% [1.0-40.0], the median PD-L1 expression on immune cells was 5.0% [1.0-11.0], and the median CPS – 18.0 [3.0-7.8]. Univariate and multivariate analyses revealed a significant negative effect of PD-L1 expression on immune cells ≤ 7% on OS (HR 0.66; 95% CI 0.45-0.93; p = 0.0498); PD-L1 expression in tumor cells ≤ 15% (HR 0.65; 95% CI 0.43-0.98; p = 0.0416) and CPS ≤ 21 (HR 0.62; 95% CI 0.44-0.92; p = 0.0183) for PFS. PD-L1 expression in tumor cells ≤ 6% (HR 0.71; 95% CI 0.47-1.08; p = 0.1096) and CPS ≤ 7 (RR 0.67; 95% CI 0.44-1.01; p = 0.0575) had a confident tendency to negative impact on OS.Conclusion. Positive PD-L1 expression in tumor and immune cells as well as CPS are effective additional factors in the prognosis of the disease course, OS and PFS in patients with OCSCC.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Haiyan Song ◽  
Zhaoke Dong ◽  
Lili Li ◽  
Zengbin Lu ◽  
Chao Li ◽  
...  

Abstract Apolygus lucorum (Meyer-Dür) (Hemiptera: Miridae) tends to feed on young plant tissues. To explore the relationship between stylet probing behaviors of adult A. lucorum and conditions of cotton leaves, we conducted an experiment using electropenetrography (EPG). Behaviors were recorded on four cotton varieties, in relation to thickness and biochemical traits of differently-aged leaves. Cotton leaf age had a significant effect on the probing behavior of A. lucorum but cotton variety did not. One-day-old leaves of A. lucorum received the highest mean number of stylet probes (penetrations) per insect, and longest mean durations per insect of combined stylet probing or its components, cell rupture and ingestion behaviors. All of the leaf traits (thickness and biochemical substances) were similar among these four cotton varieties. Leaf thickness had a significantly negative effect on the same four variables above. Gossypol and tannin also had a negative impact on combined probing duration. Redundancy analysis showed that the four EPG variables were closely related to nutrient substances (amino acids, sugar, and water) while they had the opposite relationship with plant defense substances (gossypol and tannin). On cotton in the seedling stages, A. lucorum fed more readily on the youngest, thinnest leaves in our no-choice EPG experiments. Nutrients and chemical resistance substances determined the probing duration of A. lucorum. Our findings can contribute to better understanding of patterns of feeding and host consumption by A. lucorum, ultimately improving cotton resistance to A. lucorum.


Mathematics ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1341
Author(s):  
Tinggui Chen ◽  
Lijuan Peng ◽  
Jianjun Yang ◽  
Guodong Cong

With highly developed social media, English learning Applications have become a new type of mobile learning resources, and online comments posted by users after using them have not only become an important source of intellectual competition for enterprises, but can also help understand customers’ requirements, thereby improving product functionalities and service quality, and solve the pain points of product iteration and innovation. Based on this, this paper crawled the online user comments of three typical APPs (BaiCiZhan, MoMoBeiDanCi and BuBeiDanCi), through emotion analysis and hotspot mining technology, to obtain user requirements and then the K-means clustering method was used to analyze user requirements. Finally, quantile regression is used to find out which user needs have an impact on the downloads of English vocabulary APPs. The results show that: (1) Positive comments have a more significant impact on users’ downloads behavior than negative online comments. (2) English vocabulary APPs with higher downloads, both the 5-star user ratings and the increase of emotional requirement have a negative effect on the increase in APP downloads, while the enterprise’s service requirement improvement has a positive effect on the increase of APP downloads. (3) Regarding English vocabulary APPs with average or high downloads, improving the adaptability and Appearance requirements have significant negative impact on downloads. (4) The functional requirements to improve products will have a significant positive impact on the increase in downloads of English vocabulary APPs.


2007 ◽  
Vol 75 (8) ◽  
pp. 3758-3768 ◽  
Author(s):  
Mehdi Labaied ◽  
Anke Harupa ◽  
Ronald F. Dumpit ◽  
Isabelle Coppens ◽  
Sebastian A. Mikolajczak ◽  
...  

ABSTRACT Malaria infection starts when sporozoites are transmitted to the mammalian host during a mosquito bite. Sporozoites enter the blood circulation, reach the liver, and infect hepatocytes. The formation of a parasitophorous vacuole (PV) establishes their intracellular niche. Recently, two members of the 6-Cys domain protein family, P52 and P36, were each shown to play an important albeit nonessential role in Plasmodium berghei sporozoite infectivity for the rodent host. Here, we generated p52/p36-deficient Plasmodium yoelii parasites by the simultaneous deletion of both genes using a single genetic manipulation. p52/p36-deficient parasites exhibited normal progression through the life cycle during blood-stage infection, transmission to mosquitoes, mosquito-stage development, and sporozoite infection of the salivary glands. p52/p36-deficient sporozoites also showed normal motility and cell traversal activity. However, immunofluorescence analysis and electron microscopic observations revealed that p52/p36-deficient parasites did not form a PV within hepatocytes in vitro and in vivo. The p52/p36-deficient parasites localized as free entities in the host cell cytoplasm or the host cell nucleoplasm and did not develop as liver stages. Consequently, they did not cause blood-stage infections even at high sporozoite inoculation doses. Mice immunized with p52/p36-deficient sporozoites were completely protected against infectious sporozoite challenge. Our results demonstrate for the first time the generation of two-locus gene deletion-attenuated parasites that infect the liver but do not progress to blood-stage infection. The study will critically guide the design of Plasmodium falciparum live attenuated malaria vaccines.


1984 ◽  
Vol 62 (9) ◽  
pp. 1968-1970 ◽  
Author(s):  
William G. Roland ◽  
L. Michael Coon

Recovery of intertidal Porphyra beds following hand harvest was studied near the northwest tip of the Queen Charlotte Islands, B.C. Twenty-six percent of the standing crop of Porphyra perforata J. Ag. was removed in a large plot in June 1981; no negative effect on standing crop was apparent in May 1982 as compared with the adjacent control area. There was no negative impact on percent cover of Porphyra (mostly P. perforata) within 1 year after hand harvest of seven, approximately 1-m2 plots, as compared with respective controls. Annual fluctuation in cover, biomass, and relative mix of Porphyra species was large. Porphyra cover in a small plot harvested in early June 1981 increased to 86% of the June value by mid-July 1981, indicating substantial growth of the remaining thallus fragments and small, whole plants within one season. It was concluded that sustained yield of Porphyra beds can be assured if harvest is restricted to gathering by hand.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Xianchun Zhang ◽  
Zhu Yao ◽  
Wan Qunchao ◽  
Fu-Sheng Tsai

Purpose Time pressure is the most common kind of work pressure that employees face in the workplace; the existing research results on the effect of time pressure are highly controversial (positive, negative, inverted U-shaped). Especially in the era of knowledge economy, there remains a research gap in the impact of time pressure on individual knowledge hiding. The purpose of this paper is to explore the impact of different time pressure (challenge and hindrance) on knowledge hiding and to explain why there is controversy about the effect of time pressure in the academics. Design/methodology/approach The authors collected two waves of data and surveyed 341 R&D employees in China. Moreover, they used regression analysis, bootstrapping and Johnson–Neyman statistical technique to verify research hypotheses. Findings The results show that challenge time pressure (CTP) has a significant negative effect on knowledge hiding, whereas hindrance time pressure (HTP) has a significant positive effect on knowledge hiding; job security mediates the relationship between time pressure and knowledge hiding; temporal leadership strengthen the positive impact of CTP on job security; temporal leadership can mitigate the negative impact of HTP on job security. Originality/value The findings not only respond to the academic debate about the effect of time pressure and point out the reasons for the controversy but also enhance the scholars’ attention and understanding of the internal mechanism between time pressure and knowledge hiding.


2021 ◽  
Author(s):  
Rudolf Siegel ◽  
Cornelius J. König ◽  
Veronika Lazar

Electronic monitoring is more and more widespread and affects many employees around the globe. The current meta analysis collected data of 59 independent samples (with 223 effect sizes) to estimate the effect of electronic monitoring on job satisfaction, stress, and performance. A random-effects model indicated a small negative effect of monitoring on job satisfaction, r=-.09, and a small positive effect on stress, r=.12. There was no relationship with performance, r=-.01. Even if the effects of monitoring on job satisfaction and stress are small, taking the large number of employees who are monitored for several hours a day into account, these effects may have a severe and negative impact on employees’ well-being. Performance maintenance is the main justification for the use of electronic monitoring, but the non-existing relationship of monitoring with performance questions the validity of this justification.


2019 ◽  
Vol 26 ◽  
pp. 1-10
Author(s):  
Hector Nava-Trujillo

The aim of this study was to determine the effect of clinical mastitis occurring between calving and the first service on the percentage of cows that achieve two reproductive targets: be served before 70 days postpartum and be pregnant before 110 days postpartum (dpp). Relative frequency and odds ratio (OR) with the corresponding confidence interval (CI) were calculated. Fewer mastitic cows were served before 70 dpp than non-mastitic (24.86% vs 36.59% respectively P = 0.0137); mastitic cows had lower odds to be served than non-mastitic cows (OR: 0.57; 95% CI: 0.3679-0.8938, P = 0.0141). Fewer mastitic cows became pregnant before 110 dpp than non-mastitic cows (36.72% vs 50.73%, respectively, P = 0.006) and mastitic cows had lower odds to become pregnant than non-mastitic cows (OR: 0.56; 95% CI: 0.3739-0.8495, P = 0.0062).  Negative effect of clinical mastitis on percentage of cows served only was observed in primiparous cows, with 4.76% of mastitic cows being served in comparison with 30.19% of non-mastitic cows (P = 0.0017); primiparous mastitic cows had lower odds (0.11; 95% CI: 0.0249-0.5374, P = 0.0059) to be served than non-mastitic primiparous cows. Percentage of primiparous mastitic cows pregnant before 110 dpp was lower than non-mastitic cows (16.67% vs 37.74%, P = 0.0245) and mastitic cows had only 0.3300 odds (95% CI: 0.1234-0.8822, P = 0.0271) to become pregnant that primiparous non-mastitic. In multiparous, 42.96% of mastitic and 55.26% of non-mastitic cows (P = 0.0378) became pregnant before 110 dpp and mastitic cows had 0.6098 odd (95% CI: 0.3821-0.9730, P = 0.0380) to become pregnant than non-mastitic. In conclusion, clinical mastitis reduced the possibility of cows to be served and become pregnant during the first 70 and 110 dpp respectively, and the negative impact of clinical mastitis was more harmful in primiparous cows.


Author(s):  
Elvira Vitaljevna Burtseva ◽  
Olga Chepak ◽  
Olga Kulikova

The subject of this research is the implementation of digital technologies in educational process of a university. The goal consists in studying the impact of digital technologies upon the students’ learning activities. The article presents the results of questionnaire-based survey among students by the three question pools. In the course of research, the author examines such aspects of the problem, as the positive and negative impact of technologies upon learning activities of the students of digital generation. Particular attention is given to consideration of students’ attitude on digitalization of higher education. The opinions of pedagogues on the results of conducted research are presented. The scientific novelty lies in mainstreaming the question on the negative impact of digital technologies upon learning activities of the modern generation of students that deserves special attention. On the background of common passion of the scholars of researchers and pedagogues for the ideas of digitalization of education, when digital technologies are viewed as virtually the key factor for modernization of educational process; second come the problems of growing pathological dependence of youth on digital technologies, undesired to switch to digitalized educational process to the disadvantage of communication in social networks and pleasant pastime online. The problem of the negative effect of digital technologies on learning activities must be recognized in order to find the ways for its solution.


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