The demise of grand narratives?
David Coady, James Chase in The Routledge Handbook of Applied Epistemology, 2018
Faced with today’s proliferation of different, specialized, or technical languages, Lyotard mostly argues that “all we can do” is adopt a kind of second-order stance of openness toward this multiverse. Eschewing any dreams of synthetic comprehension, we can only “gaze in wonderment at the diversity of discursive species, as we do at the diversity of plant or animal species” (26). With that said, The Postmodern Condition does introduce in its closing section a competing, first-order basis for epistemic “legitimation” (60). Lyotard labels it “paralogy”: Postmodern knowledge is not simply a tool of the authorities [sic]; it refines our sensitivity to differences and reinforces our ability to tolerate the incommensurable. Its principle is not the expert’s homology, but the inventor’s paralogy.Lyotard 1984 [1979]: xxv
The mitotic phase of spermatogenesis
C. Yan Cheng in Spermatogenesis, 2018
β-TrCP is another well characterized E3 ligase of the SCF complex that targets a number of the cell cycle and apoptosis regulators. There are two paralogs: β-TrCP1 (also known as BTRC) and β-TrCP2 (also known as Fbxw11). The two paralogs possess indistinguishable biochemical properties but are varied in their expression. β-TrCP1 demonstrated a high expression in the spermatocytes and a median expression in the spermatogonia. In contrast, β-TrCP2 showed a median expression in spermatogonia and low expression in the spermatocytes.82 Of note, the two paralogs showed nonredundant roles in the testis. Knockout of β-TrCP1 leads to impairment in meiotic progression and male subfertility.83 Intriguingly, loss of total β-TrCP activity by inducible knockdown of β-TrCP2 in β-TrCP1 knockout mice leads to an ectopic localization of spermatogonia associated with impaired cell junctions. This phenotype is attributed to the stabilization of Snail1, a bona fide substrate of β-TrCP involved in regulating the transcription of cell adhesion molecules, since knockdown of Snail1 restored the localization of spermatogonia and rescued the entire spermatogenesis. These results suggest that β-TrCP regulates the cell adhesion of spermatogonia by targeting Snail1.
Radiogenomics
Jun Deng, Lei Xing in Big Data in Radiation Oncology, 2019
Thus, several computational approaches have been developed to narrow the space of possible hypotheses about potential protein function, followed by experimental/literature-based validation, thus expediting the overall process. The first natural approach was to use sequence homology assessment tools, such as the Basic Local Alignment Search Tool (BLAST) and Position-Specific Iterative BLAST (PSI-BLAST) (Altschul et al. 1990, 1997), to transfer functional annotations to unannotated proteins from proteins having similar amino acid sequences. However, other studies demonstrated that this approach does not always yield accurate results due to the multidomain structure of proteins and the insufficiency of sequence homology to reflect the effects of the evolutionary process of gene duplication (Gerlt and Babbitt 2000; Whisstock and Lesk 2003). Thus, a much wider spectrum of data types was leveraged to expand the types, specificity, and accuracy of protein functions that can be predicted. Appropriate data analysis methods, including those from machine learning (e.g., clustering, classification, and network analysis), were employed to infer protein function form these data types. Table 13.1 lists the most well-investigated data types, as well as the most prominent data analysis approaches, used to predict protein function. For details of these data types and approaches, we refer the reader to extensive reviews (Pandey et al. 2006; Lee et al. 2007; Sharan et al. 2007) and reports of recent large-scale assessments (Radivojac et al. 2013; Jiang et al. 2016).
Role of computational and structural biology in the development of small-molecule modulators of the spliceosome
Published in Expert Opinion on Drug Discovery, 2022
Riccardo Rozza, Pavel Janoš, Angelo Spinello, Alessandra Magistrato
Regarding the RNA components of the SPL, mutations of U1 and U2 snRNA are implicated in cancer (hepatocellular carcinoma, CCL, and medulloblastoma). These mutations are responsible for 5’ cryptic splicing and intron retention events. Additionally, mutations of U1 snRNA at the 5’SS induce spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease and the leading genetic cause of newborn lethality [26,27,71–73]. The mechanism underlying SMA onset is rather complex. SMA is caused by a homozygous deletion of the survival of motor neuron-1 gene (SMN1) in chromosome 5 encoding for the SMN protein, which plays a critical role in snRNP assembly [72–74]. In humans, two paralog SMN genes exist: SMN1 and SMN2 [75]. The SMN protein produced by the SMN2 gene cannot fully compensate for the loss of SMN1 in SMA patients.
Chronic rhinosinusitis with nasal polyps: mechanistic insights from targeting IL-4 and IL-13 via IL-4Rα inhibition with dupilumab
Published in Expert Review of Clinical Immunology, 2020
In humans, the IL-4 and IL-13 genes are found at adjacent positions on chromosome 5 within a 3000 kb cluster of genes also encoding IL-3 (colony-stimulating factor), IL-5, IL-9 (T2 inflammatory regulation) and GM-CSF. The IL-4 and IL-13 genes display shared cis-(DNA sequence binding sites for transcription factors of the gene) and trans-(DNA sequences that regulate more distal genes) regulatory elements [23]. This would suggest that the IL-4 and IL-13 genes actually arose as a result of gene duplication [23]. Despite only actual overall 25% gene sequence homology they have important shared functions [24]. This would immediately suggest that IL-4 and IL-13 must have a common signaling receptor system.
MYC, MYCL, and MYCN as therapeutic targets in lung cancer
Published in Expert Opinion on Therapeutic Targets, 2020
Daniel Massó-Vallés, Marie-Eve Beaulieu, Laura Soucek
The Myc family of transcription factors consists of three paralogs: MYC, MYCN, and MYCL, which exert critical functions principally during embryogenesis and in tissue regenerative programs in the adults. Although their genes encode proteins with similar domains and function, each Myc paralog is situated on a different chromosome and expressed at distinct timings and locations during development. All Myc proteins (Myc, from now on) control cell proliferation, cell cycle progression, cell growth, metabolism, differentiation, and tissue remodeling, as well as a variety of protective checkpoint mechanisms such as growth arrest and apoptosis.
Related Knowledge Centers
- DNA Sequencing
- Gene Duplication
- Homology
- Horizontal Gene Transfer
- Nucleotide
- Amino Acid
- Nucleic Acid Sequence
- Protein Primary Structure
- History of Life
- Speciation