Human Sensation of Transcranial Electric Stimulation.

Noninvasive transcranial electric stimulation is increasingly being used as an advantageous therapy alternative that may activate deep tissues while avoiding drug side-effects. However, not only is there limited evidence for activation of deep tissues by transcranial electric stimulation, its evoked human sensation is understudied and often dismissed as a placebo or secondary effect. By systematically characterizing the human sensation evoked by transcranial alternating-current stimulation, we observed not only stimulus frequency and electrode position dependencies specific for auditory and visual sensation but also a broader presence of somatic sensation ranging from touch and vibration to pain and pressure. We found generally monotonic input-output functions at suprathreshold levels, and often multiple types of sensation occurring simultaneously in response to the same electric stimulation. We further used a recording circuit embedded in a cochlear implant to directly and objectively measure the amount of transcranial electric stimulation reaching the auditory nerve, a deep intercranial target located in the densest bone of the skull. We found an optimal configuration using an ear canal electrode and low-frequency (<300 Hz) sinusoids that delivered maximally ~1% of the transcranial current to the auditory nerve, which was sufficient to produce sound sensation even in deafened ears. Our results suggest that frequency resonance due to neuronal intrinsic electric properties need to be explored for targeted deep brain stimulation and novel brain-computer interfaces

Salvianolic acid B Relieves Oxidative Stress in Glucose Absorption and Utilization of Mice Fed High-Sugar Diet

Purpose: To evaluate the influence of Salvianolic acid B (Sal B) on  oxidative stress in mice administrated with glucose, sucrose and high-sugar diet.Methods: 40 Kunming mice were divided into four groups of 10. After a fast of 12 h, mice were treated by oral infusion respectively with physiological saline, 20 % glucose, 20 % sucrose, and 20 % glucose + 0.002 % Sal B. Blood glucose and levels of reactive oxygen species (ROS) were  determined at 0, 0.5, 1.0, 1.5, and 2.0 h after administration. Another 3 groups of 10 Kunming mice each were fed with normal diet, high-sugar diet (20 % sucrose, HSD) and HSD + 0.002 % Sal B. Four weeks later, the levels of ROS as well as antioxidant enzyme activity were determined.Results: Blood ROS showed the first peak at 0.5 h and a higher peak at 1.5 h after high glucose administration. ROS were mainly produced in liver and pancreas with the utilization of glucose. Sal B administration prevented increase in blood glucose and significantly (p < 0.05) reduced ROS produced in the process of glucose absorption and utilization, especially the latter. Sal B decrease oxidative stress induced by HSD through scavenging ROS associated with increased activity of antioxidant enzymes.Conclusion: This study demonstrates that Sal B can decrease oxidative stress in glucose absorption and utilization in HSD mice. Thus, the findings provide a basis for a potential interventional strategy for protecting against oxidative damage induced by HSD.Keywords: Salvianolic acid B, Blood glucose, Reactive oxygen species, Oxidative stress, Sugar di

BMPRIA mediated signaling is essential for temporomandibular joint development in mice

The central importance of BMP signaling in the development and homeostasis of synovial joint of appendicular skeleton has been well documented, but its role in the development of temporomandibular joint (TMJ), also classified as a synovial joint, remains completely unknown. In this study, we investigated the function of BMPRIA mediated signaling in TMJ development in mice by transgenic loss-of- and gain-of-function approaches. We found that BMPRIA is expressed in the cranial neural crest (CNC)-derived developing condyle and glenoid fossa, major components of TMJ, as well as the interzone mesenchymal cells. Wnt1-Cre mediated tissue specific inactivation of BmprIa in CNC lineage led to defective TMJ development, including failure of articular disc separation from a hypoplastic condyle, persistence of interzone cells, and failed formation of a functional fibrocartilage layer on the articular surface of the glenoid fossa and condyle, which could be at least partially attributed to the down-regulation of Ihh in the developing condyle and inhibition of apoptosis in the interzone. On the other hand, augmented BMPRIA signaling by Wnt1-Cre driven expression of a constitutively active form of BmprIa (caBmprIa) inhibited osteogenesis of the glenoid fossa and converted the condylar primordium from secondary cartilage to primary cartilage associated with ectopic activation of Smad-dependent pathway but inhibition of JNK pathway, leading to TMJ agenesis. Our results present unambiguous evidence for an essential role of finely tuned BMPRIA mediated signaling in TMJ development

Harpin-induced expression and transgenic overexpression of the phloem protein gene AtPP2-A1 in Arabidopsis repress phloem feeding of the green peach aphid Myzus persicae

<p>Abstract</p> <p>Background</p> <p>Treatment of plants with HrpN_Ea, a protein of harpin group produced by Gram-negative plant pathogenic bacteria, induces plant resistance to insect herbivores, including the green peach aphid <it>Myzus persicae</it>, a generalist phloem-feeding insect. Under attacks by phloem-feeding insects, plants defend themselves using the phloem-based defense mechanism, which is supposed to involve the phloem protein 2 (PP2), one of the most abundant proteins in the phloem sap. The purpose of this study was to obtain genetic evidence for the function of the <it>Arabidopsis thaliana </it>(Arabidopsis) PP2-encoding gene <it>AtPP2-A1 </it>in resistance to <it>M. persicae </it>when the plant was treated with HrpN_Eaand after the plant was transformed with <it>AtPP2-A1</it>.</p> <p>Results</p> <p>The electrical penetration graph technique was used to visualize the phloem-feeding activities of apterous agamic <it>M. persicae </it>females on leaves of Arabidopsis plants treated with HrpN_Eaand an inactive protein control, respectively. A repression of phloem feeding was induced by HrpN_Eain wild-type (WT) Arabidopsis but not in <it>atpp2-a1</it>/E/142, the plant mutant that had a defect in the <it>AtPP2-A1 </it>gene, the most HrpN_Ea-responsive of 30 <it>AtPP2 </it>genes. In WT rather than <it>atpp2-a1</it>/E/142, the deterrent effect of HrpN_Eatreatment on the phloem-feeding activity accompanied an enhancement of <it>AtPP2-A1 </it>expression. In PP2OETAt (<it>AtPP2-A1</it>-overexpression transgenic <it>Arabidopsis thaliana</it>) plants, abundant amounts of the <it>AtPP2-A1 </it>gene transcript were detected in different organs, including leaves, stems, calyces, and petals. All these organs had a deterrent effect on the phloem-feeding activity compared with the same organs of the transgenic control plant. When a large-scale aphid population was monitored for 24 hours, there was a significant decrease in the number of aphids that colonized leaves of HrpN_Ea-treated WT and PP2OETAt plants, respectively, compared with control plants.</p> <p>Conclusions</p> <p>The repression in phloem-feeding activities of <it>M. persicae </it>as a result of <it>AtPP2-A1 </it>overexpression, and as a deterrent effect of HrpN_Eatreatment in WT Arabidopsis rather than the <it>atpp2-a1</it>/E/142 mutant suggest that <it>AtPP2-A1 </it>plays a role in plant resistance to the insect, particularly at the phloem-feeding stage. The accompanied change of aphid population in leaf colonies suggests that the function of <it>AtPP2-A1 </it>is related to colonization of the plant.</p

Identification and Characterization of Two Novel Compounds: Heterozygous Variants of Lipoprotein Lipase in Two Pedigrees With Type I Hyperlipoproteinemia

BackgroundType I hyperlipoproteinemia, characterized by severe hypertriglyceridemia, is caused mainly by loss-of-function mutation of the lipoprotein lipase (LPL) gene. To date, more than 200 mutations in the LPL gene have been reported, while only a limited number of mutations have been evaluated for pathogenesis.ObjectiveThis study aims to explore the molecular mechanisms underlying lipoprotein lipase deficiency in two pedigrees with type 1 hyperlipoproteinemia.MethodsWe conducted a systematic clinical and genetic analysis of two pedigrees with type 1 hyperlipoproteinemia. Postheparin plasma of all the members was used for the LPL activity analysis. In vitro studies were performed in HEK-293T cells that were transiently transfected with wild-type or variant LPL plasmids. Furthermore, the production and activity of LPL were analyzed in cell lysates or culture medium.ResultsProband 1 developed acute pancreatitis in youth, and her serum triglycerides (TGs) continued to be at an ultrahigh level, despite the application of various lipid-lowering drugs. Proband 2 was diagnosed with type 1 hyperlipoproteinemia at 9 months of age, and his serum TG levels were mildly elevated with treatment. Two novel compound heterozygous variants of LPL (c.3G&gt;C, p. M1? and c.835_836delCT, p. L279Vfs*3, c.188C&gt;T, p. Ser63Phe and c.662T&gt;C, p. Ile221Thr) were identified in the two probands. The postheparin LPL activity of probands 1 and 2 showed decreases of 72.22 ± 9.46% (p&lt;0.01) and 54.60 ± 9.03% (p&lt;0.01), respectively, compared with the control. In vitro studies showed a substantial reduction in the expression or enzyme activity of LPL in the LPL variants.ConclusionsTwo novel compound heterozygous variants of LPL induced defects in the expression and function of LPL and caused type I hyperlipoproteinemia. The functional characterization of these variants was in keeping with the postulated LPL mutant activity

Multiplex digital PCR: a superior technique to qPCR for the simultaneous detection of duck Tembusu virus, duck circovirus, and new duck reovirus

Duck Tembusu virus (DTMUV), duck circovirus (DuCV), and new duck reovirus (NDRV) have seriously hindered the development of the poultry industry in China. To detect the three pathogens simultaneously, a multiplex digital PCR (dPCR) was developed and compared with multiplex qPCR in this study. The multiplex dPCR was able to specifically detect DTMUV, DuCV, and NDRV but not amplify Muscovy duck reovirus (MDRV), Muscovy duck parvovirus (MDPV), goose parvovirus (GPV), H4 avian influenza virus (H4 AIV), H6 avian influenza virus (H6 AIV), and Newcastle disease virus (NDV). The standard curves showed excellent linearity in multiplex dPCR and qPCR and were positively correlated. The sensitivity results showed that the lowest detection limit of multiplex dPCR was 1.3 copies/μL, which was 10 times higher than that of multiplex qPCR. The reproducibility results showed that the intra- and interassay coefficients of variation were 0.06–1.94%. A total of 173 clinical samples were tested to assess the usefulness of the method; the positive detection rates for DTMUV, DuCV, and NDRV were 18.5, 29.5, and 14.5%, respectively, which were approximately 4% higher than those of multiplex qPCR, and the kappa values for the clinical detection results of multiplex dPCR and qPCR were 0.85, 0.89, and 0.86, indicating that the two methods were in excellent agreement

Altered FGF Signaling Pathways Impair Cell Proliferation and Elevation of Palate Shelves

In palatogenesis, palatal shelves are patterned along the mediolateral axis as well as the anteroposterior axis before the onset of palatal fusion. Fgf10 specifically expressed in lateral mesenchyme of palate maintains Shh transcription in lateral epithelium, while Fgf7 activated in medial mesenchyme by Dlx5, suppressed the expansion of Shh expression to medial epithelium. How FGF signaling pathways regulate the cell behaviors of developing palate remains elusive. In our study, we found that when Fgf8 is ectopically expressed in the embryonic palatal mesenchyme, the elevation of palatal shelves is impaired and the posterior palatal shelves are enlarged, especially in the medial side. The palatal deformity results from the drastic increase of cell proliferation in posterior mesenchyme and decrease of cell proliferation in epithelium. The expression of mesenchymal Fgf10 and epithelial Shh in the lateral palate, as well as the Dlx5 and Fgf7 transcription in the medial mesenchyme are all interrupted, indicating that the epithelial-mesenchymal interactions during palatogenesis are disrupted by the ectopic activation of mesenchymal Fgf8. Besides the altered Fgf7, Fgf10, Dlx5 and Shh expression pattern, the reduced Osr2 expression domain in the lateral mesenchyme also suggests an impaired mediolateral patterning of posterior palate. Moreover, the ectopic Fgf8 expression up-regulates pJak1 throughout the palatal mesenchyme and pErk in the medial mesenchyme, but down-regulates pJak2 in the epithelium, suggesting that during normal palatogenesis, the medial mesenchymal cell proliferation is stimulated by FGF/Erk pathway, while the epithelial cell proliferation is maintained through FGF/Jak2 pathway