ATF6α/β-mediated adjustment of ER chaperone levels is essential for development of the notochord in medaka fish.

ATF6α and ATF6β are membrane-bound transcription factors activated by regulated intramembrane proteolysis in response to endoplasmic reticulum (ER) stress to induce various ER quality control proteins. ATF6α- and ATF6β single-knockout mice develop normally, but ATF6α/β double knockout causes embryonic lethality, the reason for which is unknown. Here we show in medaka fish that ATF6α is primarily responsible for transcriptional induction of the major ER chaperone BiP and that ATF6α/β double knockout, but not ATF6α- or ATF6β single knockout, causes embryonic lethality, as in mice. Analyses of ER stress reporters reveal that ER stress occurs physiologically during medaka early embryonic development, particularly in the brain, otic vesicle, and notochord, resulting in ATF6α- and ATF6β-mediated induction of BiP, and that knockdown of the α1 chain of type VIII collagen reduces such ER stress. The absence of transcriptional induction of several ER chaperones in ATF6α/β double knockout causes more profound ER stress and impaired notochord development, which is partially rescued by overexpression of BiP. Thus ATF6α/β-mediated adjustment of chaperone levels to increased demands in the ER is essential for development of the notochord, which synthesizes and secretes large amounts of extracellular matrix proteins to serve as the body axis before formation of the vertebra

Major histocompatibility complex (Mhc) class Ib gene duplications, organization and expression patterns in mouse strain C57BL/6

<p>Abstract</p> <p>Background</p> <p>The mouse has more than 30 <it>Major histocompatibility complex </it>(<it>Mhc</it>) class Ib genes, most of which exist in the <it>H2 </it>region of chromosome 17 in distinct gene clusters. Although recent progress in <it>Mhc </it>research has revealed the unique roles of several <it>Mhc </it>class Ib genes in the immune and non-immune systems, the functions of many class Ib genes have still to be elucidated. To better understand the roles of class Ib molecules, we have characterized their gene duplication, organization and expression patterns within the <it>H2 </it>region of the mouse strain C57BL/6.</p> <p>Results</p> <p>The genomic organization of the <it>H2-Q</it>, -<it>T </it>and -<it>M </it>regions was analyzed and 21 transcribed <it>Mhc </it>class Ib genes were identified within these regions. Dot-plot and phylogenetic analyses implied that the genes were generated by monogenic and/or multigenic duplicated events. To investigate the adult tissue, embryonic and placental expressions of these genes, we performed RT-PCR gene expression profiling using gene-specific primers. Both tissue-wide and tissue-specific gene expression patterns were obtained that suggest that the variations in the gene expression may depend on the genomic location of the duplicated genes as well as locus specific mechanisms. The genes located in the <it>H2-T </it>region at the centromeric end of the cluster were expressed more widely than those at the telomeric end, which showed tissue-restricted expression in spite of nucleotide sequence similarities among gene paralogs.</p> <p>Conclusion</p> <p>Duplicated <it>Mhc </it>class Ib genes located in the <it>H2-Q</it>, -<it>T </it>and -<it>M </it>regions are differentially expressed in a variety of developing and adult tissues. Our findings form the basis for further functional validation studies of the <it>Mhc </it>class Ib gene expression profiles in specific tissues, such as the brain. The duplicated gene expression results in combination with the genome analysis suggest the possibility of long-range regulation of <it>H2-T </it>gene expression and/or important, but as yet unidentified nucleotide changes in the promoter or enhancer regions of the genes. Since the <it>Mhc </it>genomic region has diversified among mouse strains, it should be a useful model region for comparative analyses of the relationships between duplicated gene organization, evolution and the regulation of expression patterns.</p

Loosely Coupled Joint Driven by SMA Coil Actuators”,

Abstract-We introduce a robotic prototype of an arm with a loosely coupled joint, modeled on the human joint. A viscoelastic object functions as cartilage and soft actuators as muscles. First, we show that although viscoelastic object affords smooth movement owing to shift in the center of rotation, the repeat accuracy of the joint is poor under open-loop control. The repeat accuracy was much improved by visual feedback. Under P control, the prototype was shown to be highly robust against mechanical disturbance owing to its good mechanical compliance

Intrasaccular Flow Disruptor-Assisted Coiling of Intracranial Aneurysms Using the Novel Contour Neurovascular Systems and NEQSTENT: A Single-Center Safety and Feasibility Study

Brain aneurysms; Endovascular treatment; Intrasaccular devicesAneurismas cerebrales; Tratamiento endovascular; Dispositivos intrasacularesAneurismes cerebrals; Tractament endovascular; Dispositius intrasacularsBackground: Intrasaccular flow disruptors (IFD) have been introduced in the treatment of intracranial aneurysms (IAs) to overcome the low aneurysm occlusion rate and the high recanalization rate of the coiling technique. Among them, the Contour Neurovascular System (CNS) and the Neqstent (NQS) were designed to reconstruct the aneurysmal neck and both can be used as assisting coiling devices. We aimed to report our preliminary experience with the flow disruptor-assisted coiling (IFD-AC) technique. Methods: We performed a retrospective analysis of prospectively collected data of all patients with IAs treated with the IFD-AC. Results: Between February 2021 and April 2022, we treated 15 IAs with the IFD-AC: 10 ruptured and 5 unruptured. The IFD-AC was successfully performed in 13 cases, with a post-operative RROC 1 in 12 cases (92.3%) and RROC 2 in 1 case (7.7%). There was one ischemic event (6.7%) and no hemorrhagic complications. Twelve patients underwent a mid-term radiologic follow-up: Ten IAs (83.4%) presented an adequate occlusion, while 2 (16.7%) had a recurrence. Conclusions: The IFD-AC, both with the CNS and the NQS, seems a safe technique with promising efficacy profile. The IFD-AC has proved to be safe without antiplatelet therapy in ruptured cases. Further studies are needed to confirm our preliminary results