Robust folding of a de novo designed ideal protein even with most of the core mutated to valine

Rie Koga, Mami Yamamoto, Takahiro Kosugi, Naohiro Kobayashi, Toshihiko Sugiki, Toshimichi Fujiwara, Nobuyasu Koga, Robust folding of a de novo designed ideal protein even with most of the core mutated to valine. Proceedings of the National Academy of Sciences. 117 (49), 31149-31156 (2020). DOI: 10.1073/pnas.2002120117

Beneficial effects of nasal high flow oxygen therapy after weaning from non-invasive ventilation: A prospective observational study

It remains unknown whether application of nasal high flow (NHF) is effective after liberation from non-invasive ventilation (NIV). This study was aimed at investigating the effect of NHF in patients ready for weaning from NIV. With institutional ethic committee approval, patients receiving NIV due to hypoxemic respiratory failure for more than 24 hours were enrolled. After passing the weaning criteria with continuous positive airway pressure (CPAP) mode [fraction of inspiratory oxygen (FIO2) ≦0.5, positive end expiratory pressure (PEEP) 4 cmH2O], patients received NHF (Flow 50 L/min, FIO2 ≦0.5) immediately after liberation from NIV. Before the initiation of the study, eight sequential patients who received oxygen via face mask after NIV treatment, served as the historical control. Respiratory parameters [partial pressure of arterial oxygen (PaO2) to FIO2 ratio (P/F ratio), respiratory rate (RR)] 1 hour after liberation from NIV were evaluated with those during NIV as the primary outcome. The frequency of rescue NIV therapy, intubation, and respiratory failure were also recorded. Nine eligible patients received NHF therapy after liberation from NIV. P/F ratio and RR did not change significantly compared with those during NIV (231 ± 43.6 versus 250.7 ± 34.2 mmHg, 20.8 ± 2.3 versus 21 ± 1.6 /min), while P/F ratio decreased significantly in the historical control group (194.3 ± 20.1 versus 255.9 ± 58.1 mmHg, p=0.013). Rescue NIV therapy, intubation, and respiratory failure never occurred in the NFH group, although two patients received NIV rescue therapy, of whom one was intubated in the historical control. NHF after liberation from NIV might be effective in patients recovering from hypoxemic respiratory failure

Effects of ezetimibe add-on therapy for high-risk patients with dyslipidemia

<p>Abstract</p> <p>Background</p> <p>Ezetimibe (Zetia^®) is a potent inhibitor of cholesterol absorption that has been approved for the treatment of hypercholesterolemia. Statin, an inhibitor of cholesterol synthesis, is the first-choice drug to reduce low-density lipoprotein-cholesterol (LDL-C) for patients with hypercholesterolemia, due to its strong effect to lower the circulating LDL-C levels. Because a high dose of statins cause concern about rhabdomyolysis, it is sometimes difficult to achieve the guideline-recommended levels of LDL-C in high-risk patients with hypercholesterolemia treated with statin monotherapy. Ezetimibe has been reported to reduce LDL-C safely with both monotherapy and combination therapy with statins.</p> <p>Results</p> <p>To investigate the effect of ezetimibe as "add-on" therapy to statin on hypercholesterolemia, we examined biomarkers and vascular endothelial function in 14 patients with hypercholesterolemia before and after the 22-week ezetimibe add-on therapy. Ezetimibe add-on therapy reduced LDL-C by 24% compared with baseline (p < 0.005), with 13 patients (93%) reaching their LDL cholesterol goals. Of the Ezetimibe add-on therapy significantly improved not only LDL-C, high-density lipoprotein-cholesterol (HDL-C), and apolipoprotein (apo)B levels, but also reduced levels of triglyceride (TG), the ratio of LDL/HDL-C, the ratio of apoB/apoA-I, and a biomarker for oxidative stress (d-ROMs). Furthermore, ezetimibe add-on therapy improved vascular endothelial function in high-risk patients with hypercholesterolemia.</p> <p>Conclusion</p> <p>In conclusion, ezetimibe as add-on therapy to statin might be a therapeutic good option for high-risk patients with atherosclerosis.</p

Endogenization and excision of human herpesvirus 6 in human genomes

Sequences homologous to human herpesvirus 6 (HHV-6) are integrated within the nuclear genome of about 1% of humans, but it is not clear how this came about. It is also uncertain whether integrated HHV-6 can reactive into an infectious virus. HHV-6 integrates into telomeres, and this has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 is located on the subtelomere of chromosome 22q (chr22q) and is required to make PIWI-interacting RNAs (piRNAs). As piRNAs block germline integration of transposons, piRNA-mediated repression of HHV-6 integration has been proposed to explain this association.In vitro, recombination of the HHV-6 genome along its terminal direct repeats (DRs) leads to excision from the telomere and viral reactivation, but the expected "solo-DR scar" has not been describedin vivo. Here we screened for integrated HHV-6 in 7,485 Japanese subjects using whole-genome sequencing (WGS). Integrated HHV-6 was associated with polymorphisms on chr22q. However, in contrast to prior work, we find that the reported MOV10L1 polymorphism is physically linked to an ancient endogenous HHV-6A variant integrated into the telomere of chr22q in East Asians. Unexpectedly, an HHV-6B variant has also endogenized in chr22q; two endogenous HHV-6 variants at this locus thus account for 72% of all integrated HHV-6 in Japan. We also report human genomes carrying only one portion of the HHV-6B genome, a solo-DR, supporting in vivo excision and possible viral reactivation. Together these results explain the recently-reported association between integrated HHV-6 and MOV10L1/piRNAs, suggest potential exaptation of HHV-6 in its coevolution with human chr22q, and clarify the evolution and risk of reactivation of the only intact (non-retro)viral genome known to be present in human germlines

A Shock-Induced Pair of Superbubbles in the High-Redshift Powerful Radio Galaxy MRC 0406-244

We present new optical spectroscopy of the high-redshift powerful radio galaxy MRC 0406$-$244 at redshift of 2.429. We find that the two extensions toward NW and SE probed in the rest-frame ultraviolet image are heated mainly by the nonthermal continuum of the active galactic nucleus. However, each extension shows a shell-like morphology, suggesting that they are a pair of superbubbles induced by the superwind activity rather than by the interaction between the radio jet and the ambient gas clouds. If this is the case, the intense starburst responsible for the formation of superbubbles could occur $\sim 1 \times 10^9$ yr ago. On the other hand, the age of the radio jets may be of the order of $\sim 10^6$ yr, being much shorter than the starburst age. Therefore, the two events, i.e., the starburst and the radio-jet activities, are independent phenomena. However, their directions of the expanding motions could be governed by the rotational motion of the gaseous component in the host galaxy. This idea appears to explain the alignment effect of MRC 0406$-$244.Comment: 4 pages (emulateapj.sty), Fig. 1 (jpeg) + Fig.2 (eps). Accepted for publications in ApJ (Letters

Whole genome sequencing of 45 Japanese patients with intellectual disability

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