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The Parasite's Way of Life
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
The ability of kinetoplastids to undergo sexual, genetic recombination has been debated for decades; traditionally, these parasites were believed to reproduce primarily or exclusively asexually. Yet with the development of modern techniques, numerous studies now indicate that most of these parasites also engage in genetic recombination. Evidence supporting sexual reproduction in trypanosomes was presented in Figure 2.1. Similar evidence also exists for Leishmania. These parasites are transmitted by sand flies in the genera Phlebotomus (in Africa and Asia) and Lutzomyia (in the Americas). In the vector, replication of a flagellated stage known as a promastigote occurs in the sand fly gut. Promastigotes are ultimately transferred to the vertebrate host as the sand fly feeds. Within the vertebrate, promastigotes are ingested by phagocytic cells such as macrophages, where they develop into amastigotes. Amastigotes also undergo extensive binary fission within the phagocytic cell. Following their release from phagocytic cells, newly formed amastigotes, may be taken up by a different cell, resulting in a new round of replication. Ultimately a sand fly may ingest an infected phagocytic cell as it feeds, completing the cycle.
The Viruses
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
The neuraminidase enables influenza virus to penetrate mucous secretions by virtue of its enzymatic activity. Neuraminidase also promotes the release of the virions as they bud from the cell surface. The envelope hemagglutinin serves to attach the virus to cells by binding to cell receptors. The virus then enters the cell in an endosomal vesicle. As the pH of the vesicle becomes acidic, the hemagglutinin changes conformation and allows fusion of the viral envelope with the endosomal membrane, resulting in uncoating and release of the viral nucleocapsid into the cell cytoplasm. Influenza viruses, unlike most RNA viruses, replicate in the cell nucleus rather than in the cytoplasm. The influenza virus has a negative stranded RNA, which is not translated directly by the host cell. Initiation of replication is possible because the virus encodes and packages its own RNA-dependent RNA polymerase. The viral RNA consists of eight different single-stranded segments, each coding for at least one of the major viral proteins. If two strains of influenza A virus infect the same cell, an interchange of entire genomic segments can occur (reassortment). Unlike classical genetic recombination, splicing and rejoining of the nucleic acid is not required in this process. Related influenza A viruses also infect animals of a variety of species, including pigs and many types of birds. These viral strains represent potential pools of genetic material for pathogenic human influenza strains by reassortment of genomic segments between animal and human influenza strains that infect a common host.
Surface Engineered Graphene Oxide and Its Derivatives
Published in Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji, Viral and Antiviral Nanomaterials, 2022
Zaira Zaman Chowdhury, Abu Nasser Faisal, Shahjalal Mohammad Shibly, Devarajan Thangadurai, Saher Islam, Jeyabalan Sangeetha
Legitimate genetic recombination for treating human diseases, as well genetic abnormalities such as cancer, Parkinson’s disease, and cystic fibrosis, necessitates the use of a vector that safeguards the DNA from degradation and enables a higher transfection efficacy (Zhang et al. 2011a). Immune system destruction, cytotoxicity, chromosomal inclusion, mutagenesis, and high input costs are the potential drawbacks associated with viral vectors. Cationic lipids, cationic polymers, and cationic peptides are regarded as nonviral gene carriers, which have relatively fewer restrictions (Guo and Huang 2011; Kim and Kim 2014). Polyethylenimine (PEI) had already been widely studied as a nonviral gene carrier due to its strong binding tendency with the nucleic acid molecules and rapid cellular absorption. It protects against disintegration and enhances endosomal liberation of the RNA or DNA (Jaeger et al. 2012; Ren et al. 2012). PEI has limited biocompatibility as well as significant toxicity. Because GO has negative charges over its surface, electrostatic repulsion between the negative charges of the phosphate structure of the DNA molecule frequently takes place. This must be mitigated by surface functionalization with the cationic polymers, such as polyethylenimine (PEI). As a result, PEI-functionalized GO may be able to solve these limitations, resulting in an efficient gene-delivery mechanism. Branched polyethylenimine (bPEI) has reduced molecular weight and lower toxicity but inadequate transfection efficiency.
Molecular engineering tools for the development of vaccines against infectious diseases: current status and future directions
Published in Expert Review of Vaccines, 2023
Wenhui Xue, Tingting Li, Ying Gu, Shaowei Li, Ningshao Xia
The Lambda Red recombination system is a powerful genetic recombination system found in bacteriophage λ, consisting of three proteins: Exo, Beta, and Gam. Exo is a 5’−3“ exonuclease that degrades single-stranded DNA (ssDNA) in a 5”−3’ direction, generating 3’ overhangs. Beta is a single-strand annealing protein that binds to the ssDNA overhangs produced by Exo and facilitates the annealing of complementary sequences [39]. Together, these proteins enable homologous recombination between two DNA molecules, rendering the Red recombination system a valuable tool for genetic manipulation, including gene knockouts, insertions, and modifications (Figure 1b). One common application of the Red system is in creating ‘knockout’ strains of bacteria, in which a specific gene is removed from the genome [40].
Challenges in antibody structure prediction
Published in mAbs, 2023
Monica L. Fernández-Quintero, Janik Kokot, Franz Waibl, Anna-Lena M. Fischer, Patrick K. Quoika, Charlotte M. Deane, Klaus R. Liedl
Antibodies are crucial components of the adaptive immune response.15 Genetic recombination and somatic hypermutation events enable the adaptive immune system to produce a vast number of antibodies against a variety of pathogens.14 To understand and optimize antigen recognition and to enable rational design of antibodies, accurate structure models are essential.16 Despite these recent advances, accurate structure prediction of antibodies remains challenging and still needs to be extensively validated. In particular, the flexible loops involved in recognizing the antigen pose a major challenge.17,18 In comparison to other protein superfamilies, the fold of antibodies is generally highly conserved.19–21 In particular, the framework of the antigen-binding fragment (Fab) is structurally almost identical for all antibodies.22,23 However, the area hardest to predict accurately is the six hypervariable loops that can form, together with several framework residues, the antigen-binding site, engaging with the respective epitope. These loops are also known as the complementarity-determining region (CDR) and provide the sequence and structure diversity essential to recognize a wide range of antigens. Five of the six loops tend to adopt canonical cluster folds based on their length and sequence composition. However, the third CDR loop of the heavy chain, the CDR-H3 loop, is the most diverse in length, sequence and structure and therefore is the most challenging loop to predict accurately.
Molecular radiobiology and the origins of the base excision repair pathway: an historical perspective
Published in International Journal of Radiation Biology, 2023
In the early 1970s, a number of laboratories, including my own, began to look at the cellular responses to the vast majority of ionizing radiation damages that included base damages, alkali- labile lesions (abasic sites) and single-strand breaks (Figure 1). As stated above, this work was stimulated originally by the studies of Setlow (Setlow and Carrier 1964), Howard Flanders (Boyce and Howard-Flanders 1964) and Hanawalt (Pettijohn and Hanawalt 1963, 1964) who showed that ultraviolet light damages in DNA could be removed and repaired in Escherichia coli. Moreover, Ruth Hill had isolated E. coli mutants that were highly sensitive to ionizing radiation as well as ultraviolet light (Hill 1958; Hill and Simson 1961). It turns out that E. coli mutants that lacked RecA, thus deficient in genetic recombination, were also sensitive to ionizing radiation and conversely, those that were radiation sensitive were also recombination deficient (Howard-Flanders and Boyce 1966; Howard-Flanders and Theriot 1966; Clark 1973). Although double strand breaks are important lethal lesions caused by ionizing radiation, they represent a small fraction of the total lesions produced (Ward 1988).