The Cytoplasmic Tail of FPC Antagonizes the Full-Length Protein in the Regulation of mTOR Pathway

FPC (fibrocystin or polyductin) is a single transmembrane receptor-like protein, responsible for the human autosomal recessive polycystic kidney disease (ARPKD). It was recently proposed that FPC undergoes a Notch-like cleavage and subsequently the cleaved carboxy(C)-terminal fragment translocates to the nucleus. To study the functions of the isolated C-tail, we expressed the intracellular domain of human FPC (hICD) in renal epithelial cells. By 3-dimensional (3D) tubulogenesis assay, we found that in contrast to tubule-like structures formed from control cells, hICD-expressing cells exclusively formed cyst-like structures. By western blotting, we showed that the Akt/mTOR pathway, indicated by increased phosphorylation of Akt at serine 473 and S6 kinase 1 at threonine 389, was constitutively activated in hICD-expressing cells, similar to that in FPC knockdown cells and ARPKD kidneys. Moreover, application of mTOR inhibitor rapamycin reduced the size of the cyst-like structures formed by hICD-expressing cells. Application of either LY294002 or wortmannin inhibited the activation of both S6K1 and Akt. Expression of full-length FPC inhibited the activation of S6 and S6 kinase whereas co-expression of hICD with full-length FPC antagonized the inhibitory effect of full-length FPC on mTOR. Taken together, we propose that FPC modulates the PI3K/Akt/mTOR pathway and the cleaved C-tail regulates the function of the full-length protein

CT and MRI imaging and interpretation of hepatic arterioportal shunts

Hepatic arterioportal shunts (HAPS) occur due to organic or functional fistulization of blood flow between arterial hepatic vasculature and venous portal systems. It is a type of hemodynamic abnormality of the liver being observed increasingly with the use of temporal imaging modalities. HAPS occur due to other underlying hepatic abnormalities including the presence of an underlying tumor or malignancy. When a HAPS is present, the appearance of these abnormalities on imaging studies suggests an underlying abnormality, must be considered atypical even if asymptomatic, and warrants careful evaluation. Over time, and as a function of degree of fistulae, symptoms and potential life-threatening complications may arise from the HAPS. These systemic complications may include the development of portal hypertension, splenomegaly, as well as accelerated metastasis in patients with malignant tumors. This manuscript reviews common underlying conditions associated with HAPS and their radiologic interpretation

Microbial community diversity and potential functionality in response to dam construction along the Three Gorge Reservoir, China

River and reservoir bacterial communities are the most basic part of river biomes and ecosystem structure, and play an important role in river biological processes. Yet, it remains unclear how highly regulated dam reservoirs affect both soil and sediment bacterial communities. A temporal distribution pattern of bacterial communities was investigated using Illumina MiSeq sequencing in a transition section of the Three Gorges Reservoir (TGR). In total, 106,682 features belong to the bacteria kingdom, encompassing 95 phyla, 228 classes, 514 orders, 871 families, 1959 genera, and 3,053 species. With water level regulation, Shannon diversity index, and observed species differed significantly, with no significant difference in Simpson evenness. Both in the high water level period (October) and the low water level period (June), Proteobacteria, Acidobacteri, and Chloroflexi were the most abundant phyla. Whereas, based on PCA plots and Circos plot, the microbial community structure has changed significantly. LEfSe method was used to identify the classified bacterial taxa with significant abundance differences between the low water level and high water level periods. KOs (KEGG Orthology) pathway enrichment analysis were conducted to investigate functional and related metabolic pathways in groups. To some extent, it can be inferred that water level regulation affects community growth by affecting the metabolism of the microbial community

Limited Regeneration Potential with Minimal Epicardial Progenitor Conversions in the Neonatal Mouse Heart after Injury

The regeneration capacity of neonatal mouse heart is controversial. In addition, whether epicardial cells provide a progenitor pool for de novo heart regeneration is incompletely defined. Following apical resection of the neonatal mouse heart, we observed limited regeneration potential. Fate-mapping of Tbx18MerCreMer mice revealed that newly formed coronary vessels and a limited number of cardiomyocytes were derived from the T-box transcription factor 18 (Tbx18) lineage. However, further lineage tracing with SM-MHCCreERT2 and Nfactc1Cre mice revealed that the new smooth muscle and endothelial cells are in fact derivatives of pre-existing coronary vessels. Our data show that neonatal mouse heart can regenerate but that its potential is limited. Moreover, although epicardial cells are multipotent during embryogenesis, their contribution to heart repair through "stem" or "progenitor" cell conversion is minimal after birth. These observations suggest that early embryonic heart development and postnatal heart regeneration are distinct biological processes. Multipotency of epicardial cells is significantly decreased after birth

The effect of music therapy on language communication and social skills in children with autism spectrum disorder: a systematic review and meta-analysis

BackgroundStudies have shown that music therapy can be used as a therapeutic aid for clinical disorders. To evaluate the effects of music therapy (MT) on language communication and social skills in children with autism spectrum disorder (ASD), a meta-analysis was performed on eligible studies in this field.MethodsA systematic search was conducted in eight databases: PubMed, Embase, Web of Science, Cochrane Library databases, the China National Knowledge Infrastructure (CNKI), Wanfang Data, the Chinese Biomedical Literature (CBM) Database, and the VIP Chinese Science and Technology Periodicals Database. The standard mean difference (SMD) values were used to evaluate outcomes, and the pooled proportions and SMD with their 95% confidence intervals (CIs) were also calculated.ResultsEighteen randomized controlled trial (RCT) studies were included, with a total of 1,457 children with ASD. This meta-analysis revealed that music therapy improved their language communication [SMD = −1.20; 95%CI –1.45, −0.94; χ2 (17) = 84.17, I2 = 80%, p < 0.001] and social skills [SMD = −1. 13; 95%CI –1.49, −0.78; χ2 (17) = 162.53, I2 = 90%, p < 0.001]. In addition, behavior [SMD = −1.92; 94%CI –2.56, −1.28; χ2 (13) = 235.08, I2 = 95%, p < 0.001], sensory perception [SMD = −1.62; 95%CI –2.17, −1.08; χ2 (16) = 303.80, I2 = 95%, p < 0.001], self-help [SMD = −2. 14; 95%CI –3.17, −1.10; χ2 (6) = 173.07, I2 = 97%, p < 0.001] were all improved.ConclusionMusic therapy has a positive effect on the improvement of symptoms in children with ASD.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/

Molecular cloning and preliminary function study of iron responsive element binding protein 1 gene from cypermethrin-resistant Culex pipiens pallens

<p>Abstract</p> <p>Background</p> <p>Insecticide resistance jeopardizes the control of mosquito populations and mosquito-borne disease control, which creates a major public health concern. Two-dimensional electrophoresis identified one protein segment with high sequence homology to part of <it>Aedes aegypti </it>iron-responsive element binding protein (IRE-BP).</p> <p>Method</p> <p>RT-PCR and RACE (rapid amplification of cDNA end) were used to clone a cDNA encoding full length IRE-BP 1. Real-time quantitative RT-PCR was used to evaluate the transcriptional level changes in the Cr-IRE strain <it>Aedes aegypti </it>compared to the susceptible strain of <it>Cx. pipiens pallens</it>. The expression profile of the gene was established in the mosquito life cycle. Methyl tritiated thymidine (³H-TdR) was used to observe the cypermethrin resistance changes in C6/36 cells containing the stably transfected IRE-BP 1 gene of <it>Cx. pipiens pallens</it>.</p> <p>Results</p> <p>The complete sequence of iron responsive element binding protein 1 (IRE-BP 1) has been cloned from the cypermethrin-resistant strain of <it>Culex pipiens pallens </it>(Cr-IRE strain). Quantitative RT-PCR analysis indicated that the IRE-BP 1 transcription level was 6.7 times higher in the Cr-IRE strain than in the susceptible strain of 4th instar larvae. The IRE-BP 1 expression was also found to be consistently higher throughout the life cycle of the Cr-IRE strain. A protein of predicted size 109.4 kDa has been detected by Western blotting in IRE-BP 1-transfected mosquito C6/36 cells. These IRE-BP 1-transfected cells also showed enhanced cypermethrin resistance compared to null-transfected or plasmid vector-transfected cells as determined by ³H-TdR incorporation.</p> <p>Conclusion</p> <p>IRE-BP 1 is expressed at higher levels in the Cr-IRE strain, and may confer some insecticide resistance in <it>Cx. pipiens pallens</it>.</p

Methylation of Hypothalamic Tsc1-mTOR Signaling in Regulation of Obesity and Obesity Resistance

The Tsc1-mTOR signaling pathway is often related to obesity, and epigenetic modification may lead to expression changes of obesity-related gene. Therefore, we aim to investigate the methylation of the Tsc1-mTOR signaling pathway in regulation of obesity susceptibility. Wistar rats were fed a normal diet or a high-fat diet to develop animal models. Protein and mRNA expression levels of Tsc1-mTOR signaling in the hypothalamus were determined by Western blot and quantitative real-time PCR. Methylation of Tsc1 gene promoter was detected by bisulfite genomic sequence. Both mRNA and protein expression levels of Tsc1 in DIO group hypothalamus were lower; mTOR and its downstream targets S6K1, 4EBP1, and S6 protein expression levels were higher than those of the DIO-R group and the chow group. The Tsc1 gene promoter methylation rate in the hypothalamus was 92.05±3.07% in the DIO group, 87.27±1.91% in the DIO-R group, and 88.18%±3.20% in the chow group, respectively, with significantly higher levels in the DIO group. Both the expression levels of Tsc1 gene promoter methylation and Tsc1-mTOR signaling pathway in the hypothalamus of DIO rats and DIO-R rats are different. These findings may shed light on the potential mechanism for the differentiation of obesity susceptibility

Study of the Judder Characteristics of Friction Material for an Automobile Clutch and Test Verification

Abstract The friction judder characteristics during clutch engagement have a significant influence on the NVH of a driveline. In this research, the judder characteristics of automobile clutch friction materials and experimental verification are studied. First, considering the stick-slip phenomenon in the clutch engagement process, a detailed 9-degrees-of-freedom (DOF) model including the body, each cylinder of the engine, clutch and friction lining, torsional damper, transmission and other driveline parts is established, and the calculation formula of friction torque in the clutch engagement process is determined. Second, the influence of the friction gradient characteristics on the amplification or attenuation of the automobile friction judder is analyzed, and the corresponding stability analysis and the numerical simulation of different friction gradient values are carried out with MATLAB/Simulink software. Finally, judder bench test equipment and a corresponding damping test program are developed, and the relationship between the friction coefficient gradient characteristics and the system damping is analyzed. After a large number of tests, the evaluation basis of the test is determined. The research results show that the friction lining with negative gradient characteristics of the friction coefficient will have a judder signal. When the friction gradient value is less than −0.005 s/m, the judder signal of the measured clutch cannot be completely attenuated, and the judder phenomenon occurs. When the friction gradient is greater than − 0.005 s/m, the judder signal can be significantly suppressed and the system connection tends to be stable

Modification of the Zn–Co double metal cyanide complex for the synthesis of carbon dioxide–derived poly(ether–carbonate) polyols

The Zn–Co double metal cyanide (DMC) complex is regarded as a promising catalyst for the copolymerization of CO2 and propylene epoxide (PO). Various methods have been adopted to improve the catalytic performance of DMC. In this study, polyvinylpyrrolidone (PVP), as a co-complexing agent, was innovatively used to modify DMC and applied to the synthesis of poly(ether–carbonate) polyols from CO2, PO, and a chain transfer agent. The modified catalysts exhibited higher catalytic activity than the catalysts prepared by conventional methods, with a nearly 10 % increase in PO conversion. The most critical breakthrough was a reduction of nearly 5 wt% in the byproduct propylene–carbonate. The results confirmed that amide groups in PVP could coordinate with active center Zn2+, providing the modified catalysts with advantages such as low-symmetry structure, high specific surface area, and strong acidity. Moreover, the dual effects of PVP coordination and dispersion led to dramatic differences in the microstructure and activity of the catalysts when added during different preparation processes of DMC. The coordination effect of PVP was dominant in the nucleation stages which affected the crystal structure and morphology, whereas, the dispersion effect was dominant in the aging stages which prevented the catalyst particles from growing and thus a higher specific surface area. This is critical for paving the way towards exploring the introduction of groups with high steric hindrance into Zn–Co complex catalysts. In addition, a detailed and in-depth insight into the structure–activity relationship of DMC for poly(ether–carbonate) polyols synthesis was summarized