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Molecular Biology Tools to Boost the Production of Natural Products
Published in Luzia Valentina Modolo, Mary Ann Foglio, Brazilian Medicinal Plants, 2019
Luzia Valentina Modolo, Samuel Chaves-Silva, Thamara Ferreira da Silva, Cristiane Jovelina da-Silva
The RNA interference (RNAi) or posttranscriptional gene silencing technology has become an important tool to speed up the breeding of medicinal plants, from which a conventional mutation breeding approach was shown to fail (Allen et al., 2004). The RNAi works by knocking down the expression of the target gene (Abbai et al., 2017). This provides an alternative to block the activity of enzymes that are encoded by a multigene family and are expressed in different plant tissues at distinct developmental stages. This technique has been employed to modulate the biosynthesis of morphine-like alkaloids (psychoactive drugs) by interfering with the activity of codeinone reductase (Allen et al., 2004). The gene that encodes for codeinone reductase was knocked down in Papaver somniferum plants (opium poppy) through DNA-directed RNAi, which resulted in the accumulation of (S)-reticuline, the precursor of isoquinoline alkaloid biosynthesis, at the expense of morphine, codeine, oripavine and thebaine (Allen et al., 2004). This same technique was used to block the activity of the berberine bridge enzyme in California poppy culture cells, also resulting in the accumulation of (S)-reticuline (Fujii et al., 2007). Recently, RNAi technology was used to elucidate the role of cytochrome CYP76AH1 in the metabolism of hairy roots of Salvia miltiorrhiza. The silencing of the CYP76AH1 gene affected the production of tanshinones (Ma et al., 2016). Therefore, this gene is a potential target for metabolic engineering in medicinal plants.
Kinetic Abnormalities of the Na+,K+ Pump in Essential Hypertension
Published in Antonio Coca, Ricardo P. Garay, Ionic Transport in Hypertension: New Perspectives, 2019
Na+,K+-ATPase belongs to a multigene family.21-23 Three α subunit ((α1, α2, α3) and two β subunit (β1, β2) isoforms have been described. Tissue-specific and developmental stage-dependent expression have been recently reviewed.21-23 Two distinct explanations have been proposed to account for the existence of several Na+,K+-ATPase isoforms differentially expressed in various tissues.24 One possible explanation for the existence of a multigene family is that it represents a selective advantage in evolution because it simplifies the problem of regulating gene expression to suit the needs of each developmental stage or each cell type of the organism. Alternatively, each isoform could be distinct from each specific functional characteristic.24
Genetic Testing of Y-Chromosome Microdeletion
Published in Nicolás Garrido, Rocio Rivera, A Practical Guide to Sperm Analysis, 2017
Jason C. Chandrapal, James M. Hotaling
The AZFc region is 3.5 Mb in length and is located between amplicons b2 and b4 (Figure 5.6). The most recognized gene for spermatogenesis within this region is the DAZ (deleted in azoospermia) gene44 (Table 5.3). This gene belongs to a multigene family and is clustered within the AZFc region.45 Additionally, DAZ is testis specific and expressed throughout all stages of spermatogenesis.46,47 Deletion of AZFc is the most common Y-chromosome microdeletion, accounting for 12% of nonobstructive azoospermia and 6% of oligoozospermia cases.11,48 The increased incidence of AZFc deletion is the result of a high arm-to-arm sequence identity (99.97%) that allows for more nonhomologous recombination. The phenotypic outcomes of complete AZFc deletions are very favorable with the potential for hypospermatogenesis. Although a majority of these cases are azoospermic, the testicular sperm retrieval rate is significant; therefore these patients are appropriate candidates for micro-TESE and ICSI.49
Reg3β: A Potential Therapeutic Target for Tissue Injury and Inflammation-Associated Disorders
Published in International Reviews of Immunology, 2022
Yuwen Cao, Yu Tian, Yueqin Liu, Zhaoliang Su
In 1979, a major protein was extracted from pancreatic stones and juices of patients suffering from chronic calcifying pancreatitis named PSP [19]. In 1984, an additional protein in rat pancreatic juice was observed, it was present in healthy rats after pancreatic duct cannulation or in rats in which experimental pancreatitis was induced by either cerulein or taurocholate, but was absent in the pancreatic juice of healthy rats. The authors refer to this protein as PAP [20]. Given the significant homology between PSP and PAP, it is assumed that both originated from the same ancestral gene [21]. Administration of nicotinamide, a poly(ADP-ribose) synthetase inhibitor, to partially pancreatectomized rats induces regeneration of pancreatic islets [22]. Terazono et al. [23] identified a novel gene encoding a 165-amino acid protein by screening the regenerating islet-derived cDNA library. Therefore, these authors proposed naming the novel gene reg, that is regenerating gene. In 1991, Rouquier et al. [24] cloned rat PSP mRNA sequences. A complete sequence identity was observed between the rat PSP transcript and the reg mRNA described by Terazono et al. [23]. Henceforth, this gene was therefore referred to as the reg/PSP gene. Several Reg and Reg-related genes were isolated from humans, rats, and mice, constituting a multigene family: the Reg family.
A Narrative Review of the Ocular Manifestations in Noonan Syndrome
Published in Seminars in Ophthalmology, 2022
Evita Evangelia Christou, Paraskevas Zafeiropoulos, Dimitrios Rallis, Maria Baltogianni, Christoforos Asproudis, Maria Stefaniotou, Vasileios Giapros, Ioannis Asproudis
It must be underlined that RAS genes constitute a multigene family. RAS proteins are small guanosine nucleotide-bound GTPases that function as a critical signaling hub within the cell; the inactive, GDP-bound RAS converts to its active GTP-bound form. Activated RAS proteins alter gene transcription and modulate function through a series of modifications. Therefore, dysregulation of the RAS/MAPK molecular pathway results in profound deleterious effects on developmental processes. Interestingly, due to a common underlying RAS/MAPK pathway pathology, the RASopathies exhibit overlapping phenotypic features. Additional mutations may affect specific locations of relevant genes resulting in distinctive phenotype. Indeed, while each syndrome in the spectrum of RASopathies has a unique phenotype, commonalities have been identified regarding the clinical characteristics. The phenotypic features may indicate a potential diagnosis, though clinical criteria have intrinsic limitations. We may not dispute that an initial clinical decision consists of challenging overlapping features and should in turn be confirmed by molecular genetic testing. Genotype-phenotype correlations may contribute to a better approach to the diagnosis of the syndromes and amelioration of treatment management in the future.5,13,20
Integration of transcriptomic and proteomic approaches for snake venom profiling
Published in Expert Review of Proteomics, 2021
Cassandra M. Modahl, Anthony J. Saviola, Stephen P. Mackessy
Venom from the rear-fanged Brown Treesnake (Boiga irregularis) is predominately composed of 3FTxs. The number of 3FTx isoforms is quite large, with 65 3FTx transcripts identified in the venom gland transcriptome of B. irregularis from Guam [8] and 58 from B. irregularis native to Indonesia [36] (both venom gland transcriptomes were from only one individual in each of these populations). There were extensive differences in 3FTx sequences between these geographic populations, with only a single 3FTx transcript found to share 100% identity between the two populations [8]. Irditoxin, a taxon-specific 3FTx complex [39], has been characterized from B. irregularis venom from Guam, and interestingly, neither venom gland transcriptomes had a transcript sequence that was 100% identical to those reported for either irditoxin A or B subunits, although transcripts were present that after translation and signal peptide removal would produce identical subunit sequences [8,36]. These results highlight the high diversity and rapid evolution of 3FTxs genes, consistent with the birth-and-death model of multigene family evolution [8,40].