infection efficiency
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Author(s):  
Jennifer T. Niones ◽  
Ryan T. Sharp ◽  
Dindo King M. Donayre ◽  
Eula Gems M. Oreiro ◽  
Alice E. Milne ◽  
...  

AbstractBacterial blight (X. oryzae pv. oryzae) is a serious disease in rice across the world. To better control the disease, it is important to understand its epidemiology and how key aspects of this (e.g. infection efficiency, and spatial spread) change according to environment (e.g. local site conditions and season), management, and in particular, variety resistance. To explore this, we analysed data on the disease progress on resistant and susceptible varieties of rice grown at four sites in the Philippines across five seasons using a combination of mechanistic modelling and statistical analysis. Disease incidence was generally lower in the resistant variety. However, we found no evidence that the primary infection efficiency was lower in resistant varieties, suggesting that differences were largely due to reduced secondary spread. Despite secondary spread being attributed to splash dispersal which is exacerbated by wind and rain, the wetter sites of Pila and Victoria in south Luzon tended to have lower infection rates than the drier sites in central Luzon. Likewise, we found spread in the dry season can be substantial and should therefore not be ignored. In fact, we found site to be a greater determinant of the number of infection attempts suggesting that other environmental and management factors had greater effect on the disease than climate. Primary infection was characterised by spatially-random observations of disease incidence. As the season progressed, we observed an emerging short-range (1.6 m–4 m) spatial structure suggesting secondary spread was predominantly short-range, particularly where the resistant variety was grown.


Author(s):  
Haijun Tang ◽  
Long Gao ◽  
Zhao Wu ◽  
Fang Meng ◽  
Xin Zhao ◽  
...  

SARS-coronavirus 2 (SARS-CoV-2), pathogen of coronavirus disease 2019 (COVID-19), is constantly evolving to adapt to the host and evade antiviral immunity. The newly emerging variants N501Y.V1 (B.1.1.7) and N501Y.V2 (B.1.351), first reported in the United Kingdom and South Africa respectively, raised concerns due to the unusually rapid global spread. The mutations in spike (S) protein may contribute to the rapid spread of these variants. Here, with a vesicular stomatitis virus (VSV)-based pseudotype system, we demonstrated that the pseudovirus bearing N501Y.V2 S protein has higher infection efficiency than pseudovirus with wildtype (WT) and D614G S protein. Moreover, pseudovirus with N501Y.V1 or N501Y.V2 S protein has better thermal stability than WT and D614G, suggesting these mutations of variants may increase the stability of SARS-CoV-2 S protein and virion. However, the pseudovirus bearing N501Y.V1 or N501Y.V2 S protein has similar sensitivity to inhibitors of protease and endocytosis with WT and D614G. These findings could be of value in preventing the spread of virus and developing drugs for emerging SARS-CoV-2 variants.


Author(s):  
Wenyang Zhou ◽  
Chang Xu ◽  
Pingping Wang ◽  
Meng Luo ◽  
Zhaochun Xu ◽  
...  

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing an outbreak of coronavirus disease 2019 (COVID-19), has been undergoing various mutations. The analysis of the structural and energetic effects of mutations on protein-protein interactions between the receptor binding domain (RBD) of SARS-CoV-2 and angiotensin converting enzyme 2 (ACE2) or neutralizing monoclonal antibodies will be beneficial for epidemic surveillance, diagnosis, and optimization of neutralizing agents. According to the molecular dynamics simulation, a key mutation N439K in the SARS-CoV-2 RBD region created a new salt bridge with Glu329 of hACE2, which resulted in greater electrostatic complementarity, and created a weak salt bridge with Asp442 of RBD. Furthermore, the N439K-mutated RBD bound hACE2 with a higher affinity than wild-type, which may lead to more infectious. In addition, the N439K-mutated RBD was markedly resistant to the SARS-CoV-2 neutralizing antibody REGN10987, which may lead to the failure of neutralization. The results show consistent with the previous experimental conclusion and clarify the structural mechanism under affinity changes. Our methods will offer guidance on the assessment of the infection efficiency and antigenicity effect of continuing mutations in SARS-CoV-2.


2021 ◽  
Author(s):  
Giorgio Medici ◽  
Marianna Tassinari ◽  
Giuseppe Galvani ◽  
Stefano Bastianini ◽  
Laura Gennaccaro ◽  
...  

No therapy is currently available for CDKL5 (cyclin-dependent kinase-like 5) deficiency disorder (CDD), a severe neurodevelopmental disorder caused by mutations in the CDKL5 gene. Although delivery of a wild-type copy of the mutated gene to cells represents the most curative approach for a monogenic disease, proof-of-concept studies highlight significant efficacy caveats for brain gene therapy. Herein, we used a secretable TATk-CDKL5 protein to enhance the efficiency of a gene therapy for CDD. We found that, although AAVPHP.B_Igk-TATk-CDKL5 and AAVPHP.B_CDKL5 vectors had similar brain infection efficiency, the AAVPHP.B_Igk-TATk-CDKL5 vector led to a higher CDKL5 protein replacement due to secretion and transduction of the TATk-CDKL5 protein into the neighboring cells. Importantly, Cdkl5 KO mice treated with the AAVPHP.B_Igk-TATk-CDKL5 vector showed a behavioral and neuroanatomical improvement in comparison with vehicle-treated Cdkl5 KO mice or Cdkl5 KO mice treated with the AAVPHP.B_CDKL5 vector, indicating that a gene therapy based on a secretable recombinant TATk-CDKL5 protein is more effective at compensating Cdkl5-null brain defects than gene therapy based on the expression of the native CDKL5.


2021 ◽  
Author(s):  
Zaozao Wang ◽  
Bin Kang ◽  
Qianqian Gao ◽  
Lei Huang ◽  
Yingcong Fan ◽  
...  

Abstract Background Mutated KRAS promotes the activation of mitogen-activated protein kinase (MAPK) pathway and the progression of colorectal cancer (CRC) cells. Aberrant activation of phosphatidylinositol 3‑kinase (PI3K) pathway strongly attenuates the efficacy of MAPK suppression in KRAS-mutated CRC cells. The development of a novel strategy targeting dual-pathway is therefore highly essential for the therapy of KRAS-mutated CRC cells. Methods In this study, a quadruple-depleting system for KRAS, MEK1, PIK3CA, and mammalian target of rapamycin (MTOR) genes based on Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/SaCas9 was developed. Serotype 5 of adenovirus (ADV5) was used as packaging virus for systemic delivery of the CRISPR system. To enhance infection efficiency and specificity of ADV5 to CRC cells and reduce its non-specific tissue tropism, two engineered proteins, an adaptor and a protector were synthesized and formed an ADV-protein complex (APC) when delivered the quadruple-editing system intravenously in vivo. Results The quadruple-editing significantly inhibited MAPK and PI3K pathways in CRC cells with oncogenic mutations of KRAS and PIK3CA or with KRAS mutation and compensated PI3K activation. Compared with MEK and PI3K/MTOR inhibitors, the quadruple-editing induced more significant survival inhibition on primary CRC cells with oncogenic mutations of KRAS and PIK3CA. The adaptor protein which specifically targeting epithelial cell adhesion molecule (EpCAM) could dramatically enhance infection efficiency of ADV5 to CRC cells. and the protector protein could significantly reduce the off-targeting tropisms in a variety of organs. Moreover, the quadruple-editing intravenously delivered by APC significantly blocked dual-pathway and tumor growth, without influencing normal tissues in cell- and patient-derived xenograft models of KRAS-mutated CRC cells. Conclusions APC-delivered quadruple-editing of MAPK and PI3K pathways effectively and specifically blocked the progression of KRAS-mutated CRC cells.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Timra D. Gilson ◽  
Ryan T. Gibson ◽  
Elliot J. Androphy

Abstract Human papillomavirus (HPV) L1 and L2 capsid proteins self-assemble into virions capable of efficiently packaging either its 8 kilobase genome or non-viral DNA. The ability of HPV capsids to package non-viral DNA makes these a useful tool for delivering plasmids to study proteins of interest in a variety of cell types. We describe optimization of current methods and present new protocols for using HPV capsids to deliver non-viral DNA thereby providing an alternative to DNA transfection. Using keratinocyte generated extracellular matrices can enhance infection efficiency in keratinocytes, hepatocytes and neuronal cells. Furthermore, we describe a suspension-based efficient technique for infecting different cell types.


2020 ◽  
Vol 76 ◽  
pp. 102065 ◽  
Author(s):  
Ana Liempi ◽  
Christian Castillo ◽  
Lisvaneth Medina ◽  
Norbel Galanti ◽  
Juan Diego Maya ◽  
...  

Plant Disease ◽  
2020 ◽  
Vol 104 (6) ◽  
pp. 1817-1823 ◽  
Author(s):  
F. Shahoveisi ◽  
L. E. del Río Mendoza

The impact of wetness duration and incubation temperatures on Sclerotinia sclerotiorum ascospore germination and ascosporic infection efficiency were evaluated. Ascospore germination was optimal when incubated in continuous moisture (free water) at 21°C. Significantly lower germination was observed at 10 or 30°C. Interrupting ascospore wet incubation was detrimental for germination. In infection efficiency studies, dry bean and canola flowers were inoculated with dry ascospores and placed on leaves of dry bean and canola plants, respectively. Dry bean plants were incubated for 196 h at 18 to 20°C in alternating 8 to 16 h wet/12 to 24 h dry periods. Canola plants were incubated for 240 h at 10, 15, 20, 25, or 30°C in alternating 6 to 18 h wet/18 to 6 h dry periods. Interrupting wet incubation delayed symptom appearance and hindered development of the epidemics on both plant types. Logistic regression models estimated at 50% the probability of disease development on dry bean and canola plants when 68 and 48 h of wet incubation at 20°C accumulated in a period of 6 days, respectively. The canola model was validated using data from field trials. Results of these studies will contribute to develop more accurate warning models for diseases caused by S. sclerotiorum.


2020 ◽  
pp. 7-13
Author(s):  
Sh. Мavlyanova ◽  
P. Mavlyanov ◽  
J. Mullakhanov ◽  
A. Ismogilov

The article presents the results of chemical, clinical and experimental studies of siliceous solutions. The results of the study showed that siliceous solutions, due to the chemical composition of medicinal minerals and REE elements, contribute to the enrichment of the chelating protein calprotectin in neutrophils, which further inhibits the growth of mixed bacterial and viral microorganisms, which leads to anti-infection efficiency.


2020 ◽  
Author(s):  
Timra D. Gilson ◽  
Ryan T. Gibson ◽  
Elliot J. Androphy

AbstractHuman papillomavirus (HPV) L1 and L2 capsid proteins self-assemble into virions capable of efficiently packaging either its 8 kilobase genome or non-viral DNA. The ability of HPV capsids to package non-viral DNA makes these a useful tool for delivering plasmids to study proteins of interest in a variety of cell types. We describe optimization of current methods and present new protocols for using HPV capsids to deliver non-viral DNA thereby providing an alternative to DNA transfection. Using keratinocyte generated extracellular matrices can enhance infection efficiency in keratinocytes, hepatocytes and neuronal cells. Furthermore, we describe a suspension-based efficient technique for infecting different cell types.


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