China
Africa
Explore chapters and articles related to this topic
Applications of imaging genomics beyond oncology
Published in Ruijiang Li, Lei Xing, Sandy Napel, Daniel L. Rubin, Radiomics and Radiogenomics, 2019
Xiaohui Yao, Jingwen Yan, Li Shen
As with many other complex diseases, a substantial progress in the discovery of genetic factors contributing to the pathology of bipolar disease has been achieved by genome-wide association studies. Testing 1.8 million variants in 4,387 cases and 6,209 controls, Ferreira et al. identified the region of ankyrin 3 (ANK3) and calcium voltage-gated channel subunit alpha1 C (CACNA1C) in strong association with disease risk [138]. The Psychiatric Genome-Wide Association Study Consortium Bipolar Disorder Working Group (PGC-BD) later reported results with an even larger sample size [139] where genotype data were assembled from a combined analysis of 16,731 samples. They successfully confirmed the genome-wide significance of CACNA1C and identified several other genetic regions, such as teneurin transmembrane protein (TENM4 [ODZ4]), ANK3,and spectrin repeat containing nuclear envelope protein 1 (SYNE1), to be related with bipolar. However, in the subsequent replication study with 46,912 samples, only 18 SNPs from CACNA1C and ODZ4 showed significant signals with the same effect direction. Results from a recent GWAS based on Japanese population support nuclear factor I X (NFIX), mitotic arrest deficient 1 like 1 (MAD1L1), tetratricopeptide repeat and ankyrin repeat containing 1 (TRANK1), and ODZ4 as susceptible genes associated with bipolar disease risk [140].
Molecular mechanisms that change synapse number
Published in Journal of Neurogenetics, 2018
Alicia Mansilla, Sheila Jordán-Álvarez, Elena Santana, Patricia Jarabo, Sergio Casas-Tintó, Alberto Ferrús
A structurally related family of GPCRs is the latrophilin (LPHN) characterized by their high affinity binding to Teneurins, a ubiquitous group of multifunctional transmembrane proteins represented in vertebrates by four members. All Teneurin genes encode in their terminal exons small peptides that can bind to Teneurin C termini, TCAP1–4. TCAP-1 interacts with LPHN, through the association with β-dystroglycan, to induce a tissue-dependent signal cascade that modulates cytoskeletal dynamics. TCAP-1 reduces stress-induced behaviours associated with anxiety, addiction and depression in a variety of models, in part, by regulating synaptic plasticity (Woelfle, D'Aquila, Pavlovic, Husic, & Lovejoy, 2015).
Genome-Wide Repertoire of Transfer RNA-Derived Fragments in a Mouse Model of Age-Related Cataract
Published in Current Eye Research, 2022
Guowei Zhang, Lihua Kang, Pengfei Li, Qiliang Ran, Xiang Chen, Min Ji, Huaijin Guan
To further explore whether the 5 validated tRFs could play a role in ARC development, we first identified their potential target genes according to Miranda algorithms and TargetScan. As shown in Figure 4(A), the target genes were mostly involved in Axon guidance and Hippo signaling pathway through KEGG pathway analysis. Meanwhile, they were mainly associated with the cellular process in BP, intracellular anatomical structure in CC, and protein binding in MF (Figure 4(B)). As tRFs could lead Ago complexes to repress target gene expressions by exerting microRNA-like functions,16 we then focused on the reduced DE target genes of the 5 validated tRFs and obtained 25 downregulated target genes via the Venn diagram (Figure 4(C)). KEGG pathway analysis revealed that the filtered genes were primarily involved in Focal adhesion, ECM-receptor interaction, and PI3K-Akt signaling pathway (Figure 4(D)). Furthermore, the BP of the selected tRFs-targeted DE genes chiefly included camera-type eye development and sensory organ development. There were six genes involved in the two pathways, including aldehyde dehydrogenase 1A1 (Aldh1a1), bone morphogenetic protein 7 (Bmp7), crystallin beta-gamma domain containing 3 (Crybg3), platelet-derived growth factor receptor Alpha (Pdgfra), teneurin transmembrane protein 3 (Tenm3) and twisted gastrulation BMP signaling modulator 1 (Twsg1). The CC of the filtered genes was largely located in the collagen-containing extracellular matrix and extracellular space. In MF, the filtered genes are mostly associated with carbohydrate binding and protein binding (Figure 4(E)). Finally, the interaction network between the 5 validated tRFs and the 25 downregulated target genes was constructed utilizing Cytoscape. The result showed that tRF-1:30-Gly-GCC-1, tRF-1:31-iMet-CAT-1-M2, and tRF-1:31-Gly-CCC-2 might target the same gene Tenm3 (Figure 4(F)).
Opportunities and challenges for drug discovery in modulating Adhesion G protein-coupled receptor (GPCR) functions
Published in Expert Opinion on Drug Discovery, 2020
Andrey D. Bondarev, Misty M. Attwood, Jörgen Jonsson, Vladimir N. Chubarev, Vadim V. Tarasov, Helgi B. Schiöth
The receptors of aGPCR family are primarily known to interact with cellular and matricellular ligands [15] via four mechanisms [7] that can be grouped into two categories based on the spatial configuration of signaling activation. The first category includes mechanisms I and II, with both involving receptor-ligand interactions in cis-configuration, which result in signaling induction within the aGPCR-expressing cell. The second category includes mechanisms III and IV, which includes ligand-receptor interactions in cis- and trans-configurations, which can induce signaling in cells expressing the aGPCR (cis) or in cells either in contact with or distant from the cell expressing the receptor (trans). Mechanism I involves the interaction of an aGPCR with a soluble ligand which then induces Stachel sequence-mediated activation in a manner comparable to the other GPCRs families [17]. Examples of ligands involved are WNT-7 [18], chondroitin sulfate B [19], C1qL4 [20], L-phenylalanine [21], collagen III [22] and the cellular prion protein C (PrP (C)) [23]. Mechanism II is an example of matricellular interactions that occurs between aGPCRs and proteins in the extracellular matrix such as collagen III [22], collagen IV [24], and laminin-211 [25] which result in activation through mechanical perturbations. Mechanism III involves the activation and subsequent release of an aGPCR’s NTF region [26] which acts as a ligand that can modulate distant cell functions [27]. This mechanism is currently only known to be represented by vasculostatins, such as Vstat120 [28]. Mechanism IV involves cell–cell interactions between aGPCRs and other membrane proteins, such as neurexins [29], CD55 [30], CD90 [31], Lasso/teneurin-2 [32], CD81 [33], stabilin-2 [20], and LPAR1 [34]. Table 1 summarizes the currently available evidence regarding cleavability, NTF interactions and signaling partners of aGPCRs.