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Transforming Growth Factor-α and Epidermal Growth Factor
Published in Jason Kelley, Cytokines of the Lung, 2022
Another indirect line of evidence linking the EGF family of growth factors to morphogenesis is the striking sequence homology that they share with homeotic genes of lower eukaryotes. For example, the drosophila homeotic gene Notch, which is essential for differentiation of the ectoderm into neural and epidermal tissues, contains 36 EGF-like repeats within its putative extracellular domain (Wharton et al., 1985). Similarly, the nematode homeotic gene lin-12, required for normal cell fate switching during reproductive system development, consists of 11 EGF-like repeats (Greenwald, 1985). The drosophilia gene torpedo, which is involved in establishment of the embryonic dorsal–ventral axis, is a transmembrane protein with an extracellular domain and a tyrosine kinase domain homologous to those of the EGF receptor (Price et al., 1989). These analogies are based on sequence similarities of the genes, without direct biochemical evidence that the mechanisms of signal transduction by the homeotic gene products are similar to those utilized by EGF. Nonetheless, the homology shared between these morphogenically essential genes and EGF or its receptor implicate this growth factor family in developmental regulation.
Impact of Endosymbionts on Antimicrobial Properties of Medicinal Plants
Published in Mahendra Rai, Chistiane M. Feitosa, Eco-Friendly Biobased Products Used in Microbial Diseases, 2022
Flávia Figueira Aburjaile, José Ribamar Costa Ferreira-Neto, Thamara de Medeiros Azevedo, Juan Carlos Ariute, Jéssica Barboza da Silva, Roberta Lane de Oliveira Silva, Valesca Pandolfi, Ana Maria Benko-Iseppon
Hologenomics aims to understand this interaction and how molecular mechanisms may have helped in the adaptation and evolution over time to the generation of the many existing species, including the global study of the genomes of the hosts and their microbiota (microbiomes). Among the main events, the horizontal gene transfer, microbial amplification and acquisition of new symbionts (Douglas et al. 2016; Zilber-Rosenberg and Rosenberg 2008) can be mentioned. The latter is causally linked to the pan and core microbiome, which are essential genes shared between these microbial communities and are transferred and can modulate several crucial functions in the organism. Studies show that part of the microbiome (core microbiome) is always transferred from generation to generation, emphasizing that they are species or population-specific and may play an essential adaptive role.
The Stress Response and Stress Proteins
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Martin E. Feder, Dawn A. Parsell, Susan L. Lindquist
Can tolerance be engineered in multicellular animal models? Gene targeting is one technique that may soon provide answers to this question, but it is presently limited to a few model systems. Without targeting, however, insertion of transgenes in germ-line transformation experiments may inadvertently disrupt essential genes or alter their expression, which can obfuscate the phenotype of the transgene. Golic and Lindquist35 developed an approach that can alleviate this difficulty: The genome is transformed with a construct bearing a transgene of interest between two site-specific recombination targets from yeast. A separate transgene construct bears the region coding for the yeast FLP recombinase protein under control of an inducible promoter. When induced, FLP recombinase will catalyze recombination between sister chromatids bearing FLP recombination targets, producing a chromosome carrying multiple copies of the transgene or a chromosome lacking extra copies but interrupted at the exact same point as the extra copy chromosome. Multiple recombination events can be used to create an allelic series of chromosomes with a common point of transgene disruption but differing in transgene number. Subsequent genetic crosses can then isolate these chromosomes.
Therapeutic potential of RUNX1 and RUNX2 in bone metastasis of breast cancer
Published in Expert Opinion on Therapeutic Targets, 2023
Scientists mainly focus on two aspects of osteoclasts and osteoblasts in the process of bone metastasis for target identification and targeted drug development. For osteoclasts, their role in driving bone metastasis in breast cancer is widely recognized. In the vicious cycle of bone metastasis, as osteoclasts are activated directly or indirectly by tumor cells, they promote enhanced bone metastasis. During metastasis, RANK/RANKL and CSF-1/CSF-1 R activate key transcription factors, which can regulate the expression of key genes (DC-STAMP, TRAP, histone K, MMP9, calcitonin receptor, and avb3) that enhance osteoclast function. Therefore, scientists are currently developing targeted drugs for these essential genes or substances. Osteoblasts, on the other hand, play a crucial role in the process of bone metastasis. Its two targets RUNX1 and RUNX2 are involved in tumor development. Currently, there are some targeted drugs, such as AI-1047, CADD522, XRK3F2, L-Quebrachitol, Muramyl dipeptide, and L-ascorbic acid 2-phosphate sesquimagnesium salt. These drugs are primarily for RUNX1 and RUNX2, but they are not yet officially available for breast cancer and their use in cancer has not been pioneered. As we learn more about breast cancer development and bone metastasis, the pathogenesis of RUNX family and treatment resistance would require further research.
Atrazine neural and reproductive toxicity
Published in Toxin Reviews, 2022
Hamidreza Sadeghnia, Sara Shahba, Alireza Ebrahimzadeh-Bideskan, Shabnam Mohammadi, Amir Mohammad Malvandi, Abbas Mohammadipour
Some studies have also shown that atrazine exposure results in morphological changes in testis efferent ductules. Martins-Santos et al. (2018) reported luminal dilation, reduced epithelial height, and disruption of the epithelial homeostasis in rats' efferent ductules after atrazine exposure (Martins-Santos et al. 2018). These morphological changes may be due to the atrazine-induced downregulation of genes involved in lipid metabolism, molecular transport, and cell morphology (Wirbisky et al. 2016a). Also, atrazine-induced DNA hypomethylation in testis may be involved in morphological abnormalities. Atrazine could decrease DNA methylation in gonads by upregulating the MBD2 and downregulating the DNMTs expression (Xing et al. 2015). Therefore, DNA hypomethylation could lead to dysregulation of essential genes' expression, causing abnormalities in testis function.
Transposon mutagenesis in oral streptococcus
Published in Journal of Oral Microbiology, 2022
Yixin Zhang, Zhengyi Li, Xin Xu, Xian Peng
Van Opijnen et al. first proposed Tn-Seq to determine the fitness of each gene in S. pneumoniae and accurately quantified the genetic interactions across the genome [20]. The genomes of S. sanguinis and S. mutans have also been analysed for gene essentiality. In fact, 9% of the S. sanguinis SK36 genome is essential for translation, transcription, glycan biosynthesis, protein folding, sorting, and degradation [48]. In S. mutans UA159, 11% of the genome is essential and genes encode products that are closely associated with replication, translation, cell wall synthesis, and lipid metabolism. According to S. mutans core genome identified by Cornejo et al, 87% of the essential genes are part of the core genome, and the remaining 13% belong to an accessory genome [49,50]. Predictions indicate that most of the essential genes are part of the core genome; they encode proteins that are needed for basic biological functions and metabolism, and are conserved among strains. Figure 3 shows the major biological pathways of the essential genes in oral streptococci. Some essential genes in the accessory genome, which are also important to the gene-gene network, may be related to coping with unique environmental conditions, such as medium and culture conditions, as well as endogenous metabolic end products. Some genes are condition-specific; that is, they might be necessary for an organism to grow in one environment but not in others. Conditionally essential genes are discrepancies when the mutant libraries are cultured under different conditions, such as in rich or defined medium, acidic conditions or oxidative stress, and rodent models in vivo [51,52].