Genome-wide analysis of copy-number variation in humans with cleft lip and/or cleft palate identifies COBLL1, RIC1, and ARHGEF38 as clefting genes.

Cleft lip with or without cleft palate (CL/P) is a common birth defect with a complex, heterogeneous etiology. It is well established that common and rare sequence variants contribute to the formation of CL/P, but the contribution of copy-number variants (CNVs) to cleft formation remains relatively understudied. To fill this knowledge gap, we conducted a large-scale comparative analysis of genome-wide CNV profiles of 869 individuals from the Philippines and 233 individuals of European ancestry with CL/P with three primary goals: first, to evaluate whether differences in CNV number, amount of genomic content, or amount of coding genomic content existed within clefting subtypes; second, to assess whether CNVs in our cohort overlapped with known Mendelian clefting loci; and third, to identify unestablished Mendelian clefting genes.

TFAP2 paralogs facilitate chromatin access for MITF at pigmentation and cell proliferation genes.

In developing melanocytes and in melanoma cells, multiple paralogs of the Activating-enhancer-binding Protein 2 family of transcription factors (TFAP2) contribute to expression of genes encoding pigmentation regulators, but their interaction with Microphthalmia transcription factor (MITF), a master regulator of these cells, is unclear. Supporting the model that TFAP2 facilitates MITF's ability to activate expression of pigmentation genes, single-cell seq analysis of zebrafish embryos revealed that pigmentation genes are only expressed in the subset of mitfa-expressing cells that also express tfap2 paralogs. To test this model in SK-MEL-28 melanoma cells we deleted the two TFAP2 paralogs with highest expression, TFAP2A and TFAP2C, creating TFAP2 knockout (TFAP2-KO) cells.

Generating Zebrafish RNA-Less Mutant Alleles by Deleting Gene Promoters with CRISPR/Cas9.

Danio rerio (zebrafish), traditionally used in forward genetic screens, has in the last decade become a popular model for reverse genetic studies with the introduction of TALENS, zinc finger nucleases, and CRISPR/Cas9. Unexpectedly, homozygous frameshift mutations generated by these tools frequently result in phenotypes that are less penetrant than those seen in embryos injected with antisense morpholino oligonucleotides targeting the same gene. One explanation for the difference is that some frameshift mutations result in nonsense-mediated decay of the gene transcript, a process which can induce expression of homologous genes.

Electrospun nanofiber-based drug delivery platform: advances in diabetic foot ulcer management.

Introduction: Electrospinning is a facile and viable method for the fabrication of nanofibers. Electrospun nanofiber has a great potential in providing local drug or therapeutic molecule delivery to the wound site. The versatile nature of this technique ensures a broad scope of material used in the fabrication of nanofibers.

Assessing the viability of Soluplus® self-assembled nanocolloids for sustained delivery of highly hydrophobic lapatinib (anticancer agent): Optimisation and in-vitro characterisation.

Nanocolloids are considered ideal carriers for hydrophobic drugs owing to their core-shell structure. Lapatinib is a potential anti-cancer agent, but its clinical use is limited because of its poor aqueous solubility, thus requiring larger oral doses with the associated toxicity. Thus, in the present study, we fabricated self-assembled nanocolloidal polymeric micelles (LP-PMs) of Soluplus® and Pluronic® F127 by the thin-film hydration method and assessed their delivery potential of the hydrophobic anti-cancer drug lapatinib (LP) and optimised these nanocolloidal polymeric micelles using Quality-by-Design approach.