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1.
Appl Opt ; 54(6): 1443-52, 2015 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-25968212

RESUMO

Fresnel transform implementation methods using numerical preprocessing techniques are investigated in this paper. First, it is shown that up-sampling dramatically reduces the minimum reconstruction distance requirements and allows maximal signal recovery by eliminating aliasing artifacts which typically occur at distances much less than the Rayleigh range of the object. Second, zero-padding is employed to arbitrarily scale numerical resolution for the purpose of resolution matching multiple holograms, where each hologram is recorded using dissimilar geometric or illumination parameters. Such preprocessing yields numerical resolution scaling at any distance. Both techniques are extensively illustrated using experimental results.

2.
Mol Diagn Ther ; 26(6): 569-579, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35962910

RESUMO

Despite decades of investigation into the genetics of autism spectrum disorder (ASD), a current consensus in the field persists that ASD risk is too heterogeneous to be diagnosed by a single set of genetic variants. As such, ASD research has broadened to include assessment of other molecular biomarkers implicated in the condition that may be reflective of environmental exposures or gene by environment interactions. Epigenetic variance, and specifically differential DNA methylation, have emerged as areas of particularly high interest to ASD, as the epigenetic markers from specific chromatin loci collectively can reflect influences of multiple genetic and environmental factors and can also result in differential gene expression patterns. This review examines recent studies of the ASD epigenome, detailing common gene pathways found to be differentially methylated in people with ASD, and considers how these discoveries may inform our understanding of ASD etiology. We also consider future applications of epigenetics in ASD research and clinical practice, focusing on substratification, biomarker development, and experimental preclinical models of ASD that test causality. In combination with other -omics approaches, epigenomics allows an improved conceptualization of the multifactorial nature of ASD, and opens future lines of inquiry for both basic research and clinical practice.


Assuntos
Transtorno do Espectro Autista , Humanos , Transtorno do Espectro Autista/metabolismo , Epigenômica , Epigênese Genética , Metilação de DNA
3.
Genome Biol ; 23(1): 46, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35168652

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) involves complex genetics interacting with the perinatal environment, complicating the discovery of common genetic risk. The epigenetic layer of DNA methylation shows dynamic developmental changes and molecular memory of in utero experiences, particularly in placenta, a fetal tissue discarded at birth. However, current array-based methods to identify novel ASD risk genes lack coverage of the most structurally and epigenetically variable regions of the human genome. RESULTS: We use whole genome bisulfite sequencing in placenta samples from prospective ASD studies to discover a previously uncharacterized ASD risk gene, LOC105373085, renamed NHIP. Out of 134 differentially methylated regions associated with ASD in placental samples, a cluster at 22q13.33 corresponds to a 118-kb hypomethylated block that replicates in two additional cohorts. Within this locus, NHIP is functionally characterized as a nuclear peptide-encoding transcript with high expression in brain, and increased expression following neuronal differentiation or hypoxia, but decreased expression in ASD placenta and brain. NHIP overexpression increases cellular proliferation and alters expression of genes regulating synapses and neurogenesis, overlapping significantly with known ASD risk genes and NHIP-associated genes in ASD brain. A common structural variant disrupting the proximity of NHIP to a fetal brain enhancer is associated with NHIP expression and methylation levels and ASD risk, demonstrating a common genetic influence. CONCLUSIONS: Together, these results identify and initially characterize a novel environmentally responsive ASD risk gene relevant to brain development in a hitherto under-characterized region of the human genome.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Transtorno do Espectro Autista/genética , Transtorno Autístico/complicações , Transtorno Autístico/genética , Transtorno Autístico/metabolismo , Encéfalo/metabolismo , Metilação de DNA , Epigênese Genética , Epigenoma , Feminino , Genes Reguladores , Humanos , Recém-Nascido , Placenta/metabolismo , Gravidez , Estudos Prospectivos
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