In this study, ultrafast transient signals were detected on a single-shot basis using chirped-pulse up-conversion spectroscopy with dispersion compensation. Unlike in the conventional time-encoding ...technique using chirped pulses, distortion of the ultrafast waveform was reduced by applying dispersion compensation to the chirped probe pulses and using sum-frequency generation with the chirped readout pulses. The method was applied to terahertz time-domain spectroscopy and near-infrared pump–probe spectroscopy, providing ultrafast observations with an improved temporal resolution comparable to the transform-limited pulse durations. Terahertz waveforms, Kerr rotation signals, and phonon-polariton oscillations were measured accurately with no significant waveform distortion, thereby showing the proposed scheme to be promising for single-shot pump–probe spectroscopy in a wide range of spectroscopic applications.
HMG‐CoA reductase (HMGR) is a key enzyme in the mevalonate pathway for sterols and cytosolic isoprenoid production. Although HMGR kinases from spinach, barley, and cauliflower tissues have been ...strongly suggested as members of SNF1‐related protein kinases 1 (SnRK1), the phosphorylation and inactivation of HMGR by plant SnRK1s has not been demonstrated. In this study, we elucidated that AKIN10, an Arabidopsis SnRK1, acts as an HMGR kinase. The recombinant AKIN10 phosphorylates and inactivates AtHMGR1S using recombinant GRIK1 as the AKIN10 activator. In contrast, AKIN10‐GRIK1 fails to inactivate AtHMGR1S‐S577A, suggesting that this is achieved through Ser577 phosphorylation. Moreover, phosphorylation is detected not only in AtHMGR1S but also in AtHMGR1S‐S577A, suggesting the presence of a novel regulatory mechanism of plant HMGR.
Active participation of the older adults in the society is crucial; however, frailty prevents social participation. Meanwhile, many older adults participate daily in social activities, even with ...frailty. This study aims to examine whether older adults with frailty have lower social participation than those without frailty in Japan. We also investigated whether older adults with frailty and higher subjective health participate in society to the same extent as the general older population. This study included 1,082 Japanese individuals aged 65 years and older participating in the online survey. Participants answered questions on social participation, frailty, subjective health, and demographics.
Participants in the robust group had higher social participation rates than those in the frailty and pre-frailty groups. Meanwhile, frail older participants with higher subjective health had similar social participation as the robust participants. Many older adults acquire frailty despite their individual effort. Meanwhile, improving subjective health may be effective, even with frailty. The relationship between subjective health, frailty, and social participation is primitive and further studies are needed.
The efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) ablation for essential tremor (ET) is well known; however, no prognostic factors have been established. The authors aimed to ...retrospectively investigate MRgFUS ablation outcomes and associated factors and to define the cutoff values for each prognostic factor.
Sixty-four Japanese patients who underwent unilateral ventral intermediate nucleus thalamotomy with MRgFUS for ET were included. Follow-up evaluations were performed at 1 week and 1, 3, 6, 12, and 24 months postoperatively. Tremor suppression was evaluated using the Clinical Rating Scale for Tremor (CRST), and adverse effects were recorded postoperatively. Outcome-associated factors were examined preoperatively, intraoperatively, and postoperatively using multivariate analyses. The cutoff values for the prognostic factors were calculated using receiver operating characteristics.
Percentage improvements in the CRST scores of the affected upper limb were 82.4%, 72.2%, 68.6%, and 65.9% at 1, 3, 6, and 12 months, respectively. Preoperatively, a high skull density ratio (SDR) (p ≤ 0.047), low CRST part B score (used to assess tremors during several tasks) (cutoff value 25, p ≤ 0.041), and nonoccurrence of resting tremors (p = 0.027) were significantly associated with improved tremor control. An intraoperatively high maximum mean temperature (cutoff value 52.5°C, p ≤ 0.047), postoperatively large lesion (cutoff value 3.9 mm in the anterior-posterior direction, p ≤ 0.002; cutoff value 5.0-5.55 mm in the superior-inferior direction, p ≤ 0.026), and small transducer focus correction (p ≤ 0.015) were also associated with improved tremor control. No valid cutoff value was found for SDR. Adverse effects (limb weakness, sensory disturbance, ataxia/walking disturbance, dysgeusia, dysarthria, and facial swelling) occurred transiently and were associated with high SDR, high temperature, high number of sonication sessions, large lesion, and occurrence of resting tremor. Patients who developed leg weakness experienced greater percentage improvement in tremors at 3 months postoperatively than those who did not.
MRgFUS ablation could be used to achieve good tremor control with acceptable adverse effects in Japanese patients with ET. The relatively low SDR in Asian ethnic groups as compared with that of Western populations makes treatment difficult; however, the cutoff values obtained in this study may be useful for achieving good treatment outcomes even in such patients. Clinical trial registration no.: UMIN000026952 (University Hospital Medical Information Network).
ACPC = anterior commissure-posterior commissure; AP = anterior to posterior; CRST = Clinical Rating Scale for Tremor; ET = essential tremor; MRgFUS = magnetic resonance-guided focused ultrasound; PC = posterior commissure; PSA = posterior subthalamic area; RL = right to left; ROC = receiver operating characteristic; SDR = skull density ratio; SI = superior to inferior; T2WI = T2-weighted imaging; VIM = ventral intermediate nucleus.
Insulin resistance has been characterized as attenuation of insulin sensitivity at target organs and tissues, such as muscle and fat tissues and the liver. The insulin signaling cascade is divided ...into major pathways such as the PI3K/Akt pathway and the MAPK/MEK pathway. In insulin resistance, however, these pathways are not equally impaired. For example, in the liver, inhibition of gluconeogenesis by the insulin receptor substrate (IRS) 2 pathway is impaired, while lipogenesis by the IRS1 pathway is preserved, thus causing hyperglycemia and hyperlipidemia. It has been recently suggested that selective impairment of insulin signaling cascades in insulin resistance also occurs in the kidney. In the renal proximal tubule, insulin signaling via IRS1 is inhibited, while insulin signaling via IRS2 is preserved. Insulin signaling via IRS2 continues to stimulate sodium reabsorption in the proximal tubule and causes sodium retention, edema, and hypertension. IRS1 signaling deficiency in the proximal tubule may impair IRS1-mediated inhibition of gluconeogenesis, which could induce hyperglycemia by preserving glucose production. In the glomerulus, the impairment of IRS1 signaling deteriorates the structure and function of podocyte and endothelial cells, possibly causing diabetic nephropathy. This paper mainly describes selective insulin resistance in the kidney, focusing on the proximal tubule.
The differences between the biosynthesis of sterols in higher plants and yeast/mammals are believed to originate at the cyclization step of oxidosqualene, which is cyclized to cycloartenol in higher ...plants and lanosterol in yeast/mammals. Recently, lanosterol synthase genes were identified from dicotyledonous plant species including Arabidopsis, suggesting that higher plants possess dual biosynthetic pathways to phytosterols via lanosterol, and through cycloartenol. To identify the biosynthetic pathway to phytosterol via lanosterol, and to reveal the contributions to phytosterol biosynthesis via each cycloartenol and lanosterol, we performed feeding experiments by using 6-¹³C²H₃mevalonate with Arabidopsis seedlings. Applying ¹³C-{¹H}{²H} nuclear magnetic resonance (NMR) techniques, the elucidation of deuterium on C-19 behavior of phytosterol provided evidence that small amounts of phytosterol were biosynthesized via lanosterol. The levels of phytosterol increased on overexpression of LAS1, and phytosterols derived from lanosterol were not observed in a LAS1-knockout plant. This is direct evidence to indicate that the biosynthetic pathway for phytosterol via lanosterol exists in plant cells. We designate the biosynthetic pathway to phytosterols via lanosterol "the lanosterol pathway." LAS1 expression is reported to be induced by the application of jasmonate and is thought to have evolved from an ancestral cycloartenol synthase to a triterpenoid synthase, such as β-amyrin synthase and lupeol synthase. Considering this background, the lanosterol pathway may contribute to the biosynthesis of not only phytosterols, but also steroids as secondary metabolites.
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