IκB kinase phosphorylates cytoplasmic TDP-43 and promotes its proteasome degradation.

Cytoplasmic aggregation of TDP-43 in neurons is a pathological feature common to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We demonstrate that the IκB kinase (IKK) complex promotes the degradation of cytoplasmic TDP-43 through proteasomes. While IKKβ is a major factor in TDP-43 degradation, IKKα acts as a cofactor, and NEMO functions as a scaffold for the recruitment of TDP-43 to the IKK complex.

Synthesis of P-Modified DNA from Boranophosphate DNA as a Precursor via Acyl Phosphite Intermediates.

In this study, we successfully synthesized several kinds of -modified nucleic acids from boranophosphate DNAs via an acyl phosphite intermediate in solution and on a solid support. In the solution-phase synthesis, phosphorothioate diester, phosphotriester, and phosphoramidate diester were synthesized in a one-pot reaction from boranophosphodiester via the conversion of an acyl phosphite as a key intermediate. In addition, doubly -modified nucleic acid derivatives which were difficult to synthesize by the phosphoramidite and -phosphonate methods were also obtained by the conversion reaction.

Solid-Phase Synthesis of Boranophosphate/Phosphorothioate/Phosphate Chimeric Oligonucleotides and Their Potential as Antisense Oligonucleotides.

In this study, we successfully synthesized boranophosphate (PB), phosphorothioate (PS), and phosphate (PO) chimeric oligonucleotides (ODNs) as a candidate for the antisense oligonucleotides (ASOs). The PB/PS/PO-ODNs were synthesized utilizing -boranophosphonate, -phosphonothioate, and -phosphonate monomers. Each monomer was condensed with a hydroxy group to create -boranophosphonate, -phosphonothioate, and -phosphonate diester linkages, which were oxidized into PB, PS, and PO linkages in the final stage of the synthesis, respectively.

Graphics processing unit accelerated intensity-based optical coherence tomography angiography using differential frames with real-time motion correction.

We demonstrate intensity-based optical coherence tomography (OCT) angiography using the squared difference of two sequential frames with bulk-tissue-motion (BTM) correction. This motion correction was performed by minimization of the sum of the pixel values using axial- and lateral-pixel-shifted structural OCT images. We extract the BTM-corrected image from a total of 25 calculated OCT angiographic images.