Exome sequence analysis of affected individuals from two families with autosomal-dominant inheritance of coloboma identified two different cosegregating heterozygous nonsense mutations (c.370C>T ...p.Arg124∗ and c. 1066G>T p.Glu356∗) in YAP1. The phenotypes of the affected families differed in that one included no extraocular features and the other manifested with highly variable multisystem involvement, including hearing loss, intellectual disability, hematuria, and orofacial clefting. A combined LOD score of 4.2 was obtained for the association between YAP1 loss-of-function mutations and the phenotype in these families. YAP1 encodes an effector of the HIPPO-pathway-induced growth response, and whole-mount in situ hybridization in mouse embryos has shown that Yap1 is strongly expressed in the eye, brain, and fusing facial processes. RT-PCR showed that an alternative transcription start site (TSS) in intron 1 of YAP1 and Yap1 is widely used in human and mouse development, respectively. Transcripts from the alternative TSS are predicted to initiate at codon Met179 relative to the canonical transcript (RefSeq NM_001130145). In these alternative transcripts, the c.370C>T mutation in family 1305 is within the 5′ UTR and cannot result in nonsense-mediated decay (NMD). The c. 1066G>T mutation in family 132 should result in NMD in transcripts from either TSS. Amelioration of the phenotype by the alternative transcripts provides a plausible explanation for the phenotypic differences between the families.
We identified four different missense mutations in the single-exon gene MAB21L2 in eight individuals with bilateral eye malformations from five unrelated families via three independent exome ...sequencing projects. Three mutational events altered the same amino acid (Arg51), and two were identical de novo mutations (c.151C>T p.Arg51Cys) in unrelated children with bilateral anophthalmia, intellectual disability, and rhizomelic skeletal dysplasia. c.152G>A (p.Arg51His) segregated with autosomal-dominant bilateral colobomatous microphthalmia in a large multiplex family. The fourth heterozygous mutation (c.145G>A p.Glu49Lys) affected an amino acid within two residues of Arg51 in an adult male with bilateral colobomata. In a fifth family, a homozygous mutation (c.740G>A p.Arg247Gln) altering a different region of the protein was identified in two male siblings with bilateral retinal colobomata. In mouse embryos, Mab21l2 showed strong expression in the developing eye, pharyngeal arches, and limb bud. As predicted by structural homology, wild-type MAB21L2 bound single-stranded RNA, whereas this activity was lost in all altered forms of the protein. MAB21L2 had no detectable nucleotidyltransferase activity in vitro, and its function remains unknown. Induced expression of wild-type MAB21L2 in human embryonic kidney 293 cells increased phospho-ERK (pERK1/2) signaling. Compared to the wild-type and p.Arg247Gln proteins, the proteins with the Glu49 and Arg51 variants had increased stability. Abnormal persistence of pERK1/2 signaling in MAB21L2-expressing cells during development is a plausible pathogenic mechanism for the heterozygous mutations. The phenotype associated with the homozygous mutation might be a consequence of complete loss of MAB21L2 RNA binding, although the cellular function of this interaction remains unknown.
Improved public understanding of the ocean and the importance of sustainable ocean use, or ocean literacy, is essential for achieving global commitments to sustainable development by 2030 and beyond. ...However, growing human populations (particularly in mega-cities), urbanisation and socio-economic disparity threaten opportunities for people to engage and connect directly with ocean environments. Thus, a major challenge in engaging the whole of society in achieving ocean sustainability by 2030 is to develop strategies to improve societal connections to the ocean. The concept of ocean literacy reflects public understanding of the ocean, but is also an indication of connections to, and attitudes and behaviours towards, the ocean. Improving and progressing global ocean literacy has potential to catalyse the behaviour changes necessary for achieving a sustainable future. As part of the Future Seas project (
https://futureseas2030.org/
), this paper aims to synthesise knowledge and perspectives on ocean literacy from a range of disciplines, including but not exclusive to marine biology, socio-ecology, philosophy, technology, psychology, oceanography and human health. Using examples from the literature, we outline the potential for positive change towards a sustainable future based on knowledge that already exists. We focus on four drivers that can influence and improve ocean literacy and societal connections to the ocean: (1) education, (2) cultural connections, (3) technological developments, and (4) knowledge exchange and science-policy interconnections. We explore how each driver plays a role in improving perceptions of the ocean to engender more widespread societal support for effective ocean management and conservation. In doing so, we develop an ocean literacy toolkit, a practical resource for enhancing ocean connections across a broad range of contexts worldwide.
Brief Board and Committee Reports Wilson, Louis Round; Martel, Charles; Brigham, Harold F. ...
Bulletin of the American Library Association,
10/1933, Letnik:
27, Številka:
10
Journal Article
PDF
