BackgroundBotulinum neurotoxins (BoNTs), the causative agents for life-threatening human disease botulism, have been recognized as biological warfare agents. Monoclonal antibody (mAb) therapeutics hold considerable promise as BoNT therapeutics, but the potencies of mAbs against BoNTs are usually less than that of polyclonal antibodies (or oligoclonal antibodies). The confirmation of key epitopes with development of effective mAb is urgently needed.Methods and FindingsWe selected 3 neutralizing mAbs which recognize different non-overlapping epitopes of BoNT/B from a panel of neutralizing antibodies against BoNT/B. By comparing the neutralizing effects among different combination groups, we found that 8E10, response to ganglioside receptor binding site, could synergy with 5G10 and 2F4, recognizing non-overlapping epitopes within Syt II binding sites. However, the combination of 5G10 with 2F4 blocking protein receptor binding sites did not achieve synergistical effects. Moreover, we found that the binding epitope of 8E10 was conserved among BoNT A, B, E, and F, which might cross-protect the challenge of different serotypes of BoNTs in vivo.ConclusionsThe combination of two mAbs recognizing different receptors' binding domain in BoNTs has a synergistic effect. 8E10 is a potential universal partner for the synergistical combination with other mAb against protein receptor binding domain in BoNTs of other serotypes.
The concept of the neutrosophic set was introduced by Smarandache; it is a mathematical tool for handling problems involving imprecise, indeterminacy and inconsistent data. The notion of pseudo-BCI algebra was introduced by Dudek and Jun; it is a kind of nonclassical logic algebra and has a close connection with various noncommutative fuzzy logics. In this paper, neutrosophic set theory is applied to pseudo-BCI algebras. The new concepts of neutrosophic filter, neutrosophic normal filter, antigrouped neutrosophic filter, and neutrosophic p-filter in pseudo-BCI algebras are proposed, and their basic properties are presented. Moreover, by using the concept of (alpha, beta, gamma)-level set in neutrosophic sets, the relationships between fuzzy filters and neutrosophic filters are discussed.
Clostridium difficile (C. difficile) is a kind of obligate anaerobic gram-positive Bacillus related with intestinal diseases and antibiotic treatment. In present study, the C. difficile genome was studied employing met genomic technology. Genome sequencing identified C. difficile LCL126 has total size of 4,301,949 bp with a 27.97% of GC content. Specifically, 4119 predicted coding genes, 188 repeat sequences, 13 prophages and 8 gene islands were detected. Additionally, gene function analysis aspect of the function annotation, effector, and virulence were concluded that total of 3367 cluster of orthologous groups of proteins genes and classified into 24 categories, while the most outstanding class was metabolic process (1533) and catalytic activity (1498). The carbohydrate-active enzymes have been detected 127 genes, pathogenicity analysis revealed that 133 reduced and 22 increased virulence (hypervirulence) genes, while 54 unaffected and 10 loss of pathogenicity genes were found. Furthermore, perform the visualization and methylation expression were revealed that the dominant types comprised m4C, m5C, and m6C with the number of 6989, 36,666, and 3534, respectively. Overall, whole genome sequence information of C. difficile LCL126 was obtained and functional prediction was revealed its possible toxicological potential genes existence.
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