The Combined Effect of Electrical Stimulation and High-Load Isometric Contraction on Protein Degradation Pathways in Muscle Atrophy Induced by Hindlimb Unloading

High-load isometric exercise is considered an effective countermeasure against muscle atrophy, but therapeutic electrical stimulation for muscle atrophy is often performed without loading. In the present study, we investigated the combined effectiveness of electrical stimulation and high-load isometric contraction in preventing muscle atrophy induced by hindlimb unloading. Electrical stimulation without loading resulted in slight attenuation of muscle atrophy. Moreover, combining electrical stimulation with high-load isometric contraction enhanced this effect. In electrical stimulation without loading, inhibition of the overexpression of calpain 1, calpain 2, and MuRF-1 mRNA was confirmed. On the other hand, in electrical stimulation with high-load isometric contraction, inhibition of the overexpression of cathepsin L and atrogin-1 mRNA in addition to calpain 1, calpain 2, and MuRF-1 mRNA was confirmed. These findings suggest that the combination of electrical stimulation and high-load isometric contraction is effective as a countermeasure against muscle atrophy

Zyxin is a novel interacting partner for SIRT1

<p>Abstract</p> <p>Background</p> <p>SIRT1 is a mammalian homologue of NAD+-dependent deacetylase sirtuin family. It regulates longevity in several model organisms and is involved with cell survival, differentiation, metabolism among other processes in mammalian cells. SIRT1 modulates functions of various key targets via deacetylation. Recent studies have revealed SIRT1 protects neurons from axonal degeneration or neurodegeneration. Further, SIRT1 null mice exhibit growth retardation and developmental defects, suggesting its critical roles in neurons and development.</p> <p>Results</p> <p>To identify novel binding partners for SIRT1 in the central nervous system, we performed yeast two-hybrid screening on human fetal brain cDNA library and found that zyxin is a possible binding partner. SIRT1 and zyxin transcript were both preferentially expressed in developmental mouse brain. Zyxin accumulates in the nucleus where it is co-localized with SIRT1 after treatment with leptomycin B in COS-7 cells. Furthermore, SIRT1 deacetylates zyxin, suggesting SIRT1 could interact with nuclear-accumulated zyxin and modulate its function through deacetylation.</p> <p>Conclusion</p> <p>Zyxin could be a novel interacting partner of SIRT1. Zyxin is an adaptor protein at focal adhesion plaque, regulating cytoskeletal dynamics and signal transduction to convey signal from the ECM (extracellular matrix) to the nucleus. Our results raise the possibility that SIRT1 regulates signal transmission from ECM to the nucleus by modulating the functions of zyxin via deacetylation.</p

Effects of safflower seed extract on arterial stiffness

Safflower seed extract (SSE) contains characteristic polyphenols and serotonin derivatives (N-( p-coumaroyl) serotonin and N-feruloylserotonin), which are reported to inhibit oxidation of low-density lipoprotein (LDL), formation of atherosclerotic plaques, and improve arterial stiffness as assessed by pulse wave analysis in animal models. The effects of long-term supplementation with SSE on arterial stiffness in human subjects were evaluated. This doubleblind, placebo-controlled study was conducted in 77 males (35–65 years) and 15 postmenopausal females (55–65 years) with high-normal blood pressure or mild hypertension who were not undergoing treatment. Subjects received SSE (70 mg/day as serotonin derivatives) or placebo for 12 weeks, and pulse wave measurements, ie, second derivative of photoplethysmogram (SDPTG), augmentation index, and brachial-ankle pulse wave velocity (baPWV) were conducted at baseline, and at weeks 4, 8, and 12. Vascular age estimated by SDPTG aging index improved in the SSE-supplemented group when compared with the placebo group at four (P = 0.0368) and 12 weeks (P = 0.0927). The trend of augmentation index reduction (P = 0.072 versus baseline) was observed in the SSE-supplemented group, but reduction of baPWV by SSE supplementation was not observed. The SSE-supplemented group also showed a trend towards a lower malondialdehyde-modified-LDL autoantibody titer at 12 weeks from baseline. These results suggest long-term ingestion of SSE in humans could help to improve arterial stiffness

Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes

1,1-Difluoro-1-alkenes bearing a biaryl-2-yl group effectively underwent site-selective intramolecular iodoarylation by the appropriate cationic iodine species. Iodoarylation of 2-(2-aryl-3,3-difluoroallyl)biaryls proceeded via regioselective carbon–carbon bond formation at the carbon atoms in β-position to the fluorine substituents, thereby constructing dibenzo-fused six-membered carbocycles bearing a difluoroiodomethyl group. In contrast, 2-(3,3-difluoroallyl)biaryls underwent a similar cyclization at the α-carbon atoms to afford ring-difluorinated seven-membered carbocycles

Smoothing out Negative Tension Brane

We propose an extension of the five dimensional gravitational action with an external source in order to allow arbitrary smoothing of the negative tension brane in the Randall-Sundrum model. This extended action can be derived from a model with an auxiliary four form field coupled to the gravity. We point out a further generalization of our model in relation to tachyon condensation. A possible mechanism for radion stabilization in our model is also discussed.Comment: 12 pages, 4 figures (v1); References added (v2); Footnote 7 and a reference added, version to appear in Physics Letters B (v3

Identification of a Novel Quinvirus in the Family Betaflexiviridae That Infects Winter Wheat

Yellow mosaic disease in winter wheat is usually attributed to the infection by bymoviruses or furoviruses; however, there is still limited information on whether other viral agents are also associated with this disease. To investigate the wheat viromes associated with yellow mosaic disease, we carried out de novo RNA sequencing (RNA-seq) analyses of symptomatic and asymptomatic wheat-leaf samples obtained from a field in Hokkaido, Japan, in 2018 and 2019. The analyses revealed the infection by a novel betaflexivirus, which tentatively named wheat virus Q (WVQ), together with wheat yellow mosaic virus (WYMV, a bymovirus) and northern cereal mosaic virus (a cytorhabdovirus). Basic local alignment search tool (BLAST) analyses showed that the WVQ strains (of which there are at least three) were related to the members of the genus Foveavirus in the subfamily Quinvirinae (family Betaflexiviridae). In the phylogenetic tree, they form a clade distant from that of the foveaviruses, suggesting that WVQ is a member of a novel genus in the Quinvirinae. Laboratory tests confirmed that WVQ, like WYMV, is potentially transmitted through the soil to wheat plants. WVQ was also found to infect rye plants grown in the same field. Moreover, WVQ-derived small interfering RNAs accumulated in the infected wheat plants, indicating that WVQ infection induces antiviral RNA silencing responses. Given its common coexistence with WYMV, the impact of WVQ infection on yellow mosaic disease in the field warrants detailed investigation

Five-point Likert scaling on MRI predicts clinically significant prostate carcinoma

Background: To clarify the relationship between the probability of prostate cancer scaled using a 5-point Likert system and the biological characteristics of corresponding tumor foci. Methods: The present study involved 44 patients undergoing 3.0-Tesla multiparametric MRI before laparoscopic radical prostatectomy. Tracing based on pathological and MRI findings was performed. The relationship between the probability of cancer scaled using the 5-point Likert system and the biological characteristics of corresponding tumor foci was evaluated. Results: A total of 102 tumor foci were identified histologically from the 44 specimens. Of the 102 tumors, 55 were assigned a score based on MRI findings (score 1: n = 3; score 2: n = 3; score 3: n = 16; score 4: n = 11 score 5: n = 22), while 47 were not pointed out on MRI. The tracing study revealed that the proportion of >0.5 cm3 tumors increased according to the upgrade of Likert scores (score 1 or 2: 33 %; score 3: 68.8 %; score 4 or 5: 90.9 %, χ2 test, p 7 also increased from scale 2 to scale 5 (scale 2: 0 %; scale 3: 56.3 %; scale 4: 72.7 %; 5: 90.9 %, χ2 test, p = 0.0001). On using score 3 or higher as the threshold of cancer detection on MRI, the detection rate markedly improved if the tumor volume exceeded 0.5 cm3 (<0.2 cm3: 10.3 %; 0.2-0.5 cm3: 25 %; 0.5-1.0 cm3: 66.7 %; 1.0 < cm3: 92.1 %). Conclusions: Each Likert scale favobably reflected the corresponding tumor’s volume and Gleason score. Our observations show that “score 3 or higher” could be a useful threshold to predict clinically significant carcinoma when considering treatment options

The Subaru Deep Field Project: Lymanα\alpha Emitters at Redshift of 6.6

We present new results of a deep optical imaging survey using a narrowband filter ($NB921$) centered at $\lambda =$ 9196 \AA ~ together with $B$, $V$, $R$, $i^\prime$, and $z^\prime$ broadband filters in the sky area of the Subaru Deep Field which has been promoted as one of legacy programs of the 8.2m Subaru Telescope. We obtained a photometric sample of 58 Ly$\alpha$ emitter candidates at $z \approx$ 6.5 -- 6.6 among $\sim 180$ strong $NB921$-excess ($z^\prime - NB921 > 1.0$) objects together with a color criterion of $i^\prime - z^\prime > 1.3$. We then obtained optical spectra of 20 objects in our $NB921$-excess sample and identified at least nine Ly$\alpha$ emitters at $z \sim 6.5$ -- 6.6 including the two emitters reported by Kodaira et al. (2003). Since our Ly$\alpha$ emitter candidates are free from strong amplification of gravitational lensing, we are able to discuss their observational properties from a statistical point of view. Based on these new results, we obtain a lower limit of the star formation rate density of $\rho_{\rm SFR} \simeq 5.5 \times 10^{-4}$ $h_{0.7}$ $M_\odot$ yr$^{-1}$ Mpc$^{-3}$ at $z \approx 6.6$, being consistent with our previous estimate. We discuss the nature of star-formation activity in galaxies beyond $z=6$.Comment: 49 pages, 16 figures, PASJ, Vol. 57, No. 1, in pres

Relationships between Markers of Bone Metabolism Used in the Treatment of Osteoporosis

Various markers of bone metabolism are used in the treatment of osteoporosis as they can help assess the condition of bony tissue/bone metabolism and can help predict the likelihood of fractures and bone loss in the near future. We investigated correlations between various bone metabolism markers to ascertain which could be used as a universal marker of bone metabolism and its associated care. Subjects comprised 144 female patients treated for osteoporosis at this facility between January and December 2009, in whom the following bone metabolism markers were measured on the same day: BAP, urine NTX, OC, ucOC, and TRACP-5b. The mean age of the subjects was 71.2 years. All subjects were analyzed as an entire group (total group), and subjects were also divided into 2 groups and analyzed based on whether they were using an osteoporosis drug or not. Subjects currently being treated were included in the treated group (n=113; mean age: 71.9 years). Subjects with no treatment experience were included in the untreated group (n=31; mean age: 68.6 years). In the total group and treated group, significant correlations were revealed between BAP, urine NTX, OC, ucOC, and TRACP-5b. In the untreated group, no correlation was observed between BAP and ucOC, but correlations between BAP, urine NTX, OC, ucOC, and TRACP-5b were observed. ucOC is a marker of bone metabolism, and is also an indicator of the state of vitamin K intake. Based on the correlations with both bone resorption markers and osteoplastic markers found in this study, ucOC was found to be the best universal marker to use in the clinical setting