Split hand-split foot malformation or ectrodactyly is a heterogeneous congenital defect of digit formation. The aim of this study is the mapping of the breakpoints and a detailed molecular characterization of the candidate genes for an isolated and syndromic form of ectrodactyly, both associated with de novo apparently balanced chromosome translocations involving the same chromosome 2 band, [t(2;11)(q14.2;q14.2)] and [t(2;4)(q14.1;q35)], respectively. Breakpoints were mapped by fluorescence in situ hybridization using bacterial artificial chromosome clones. Where possible, these breakpoints were further delimited. Candidate genes were screened for pathogenic mutations and the expression levels of two of them analysed. The isolated bilateral split foot malformation-associated chromosome 2 breakpoint was localized at 120.9 Mb, between the two main candidate genes, encoding GLI-Kruppel family member GLI2 and inhibin-bB. The second breakpoint associated with holoprosencephaly, hypertelorism and ectrodactyly syndrome was mapped 2.5 Mb proximal at 118.4 Mb and the candidate genes identified from this region were the insulin-induced protein 2 and the homeobox protein engrailed-1. No clear pathogenic mutations were identified in any of these genes. The breakpoint between INHBB and GLI2 coincides with a previously identified translocation breakpoint associated with ectrodactyly. We propose a mechanism by which translocations in the 2q14.1 -q14.2 region disrupt the specific arrangement of long-range regulatory elements that control the tight quantitative spatiotemporal expression of one or more genes from the breakpoint region.
The biotransformation of the lignan (-)-cubebin by filamentous fungi Aspergillus terreus and Aspergillus niger is an efficient bioprocess for obtaining (-)-hinokinin and (-)-parabenzlactone. The relevance of getting (-)-hinokinin is due to its promising effect against oral pathogens, especially S. sanguinis (both MIC and MBC 12.5 μg/mL), and other previous reported effects against Chagas disease and as anti-inflammatory. The advantage of using fungal transformation is the use of non-toxic and/or non-pollutant reagents and/or solvents in comparison with semi-synthesis. Microbial transformation of (-)-cubebin is also important to evaluate its human metabolism, since Aspergillus species are capable of mimicking P450 reactions, providing possible products of the metabolism, which is important in the assessment of its efficacy and safety. Furthermore, the present study describes a reliable RP-HPLC method to perform quantification of (-)-hinokinin in fungal extracts. It is simple, fast, selective, linear, precise, accurate and robust according to validation guidelines.
pela amizade e pela orientação no desenvolvimento deste trabalho. Terei sempre comigo o reconhecimento pelo importante papel que tiveste neste início de vida acadêmica.Ao Dr. Carlos Augusto Pereira, o qual abriu espaço para que eu fizesse parte do grupo temático Expressão de genes heterólogos em células de dípteros: biologia molecular e engenharia de processos .
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.