Transcutaneous auricular vagus nerve stimulation improves social deficits through the inhibition of IL-17a signaling in a mouse model of autism

BackgroundMaternal exposure to inflammation is one of the causes of autism spectrum disorder (ASD). Electrical stimulation of the vagus nerve exerts a neuroprotective effect via its anti-inflammatory action. We thus investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) can enhance social abilities in a mouse model of ASD induced by maternal immune activation (MIA).MethodsASD mouse model were constructed by intraperitoneal injection of polyinosinic:polycytidylic acid (poly (I:C)). TaVNS with different parameters were tested in ASD mouse model and in C57BL/6 mice, then various behavioral tests and biochemical analyses related to autism were conducted. ASD model mice were injected with an interleukin (IL)-17a antibody into the brain, followed by behavioral testing and biochemical analyses.ResultsTaVNS reduced anxiety, improved social function, decreased the number of microglia, and inhibited M1 polarization of microglia. Additionally, taVNS attenuated the expression of the IL-17a protein in the prefrontal cortex and blood of ASD model mice. To examine the possible involvement of IL-17a in taVNS-induced neuroprotection, we injected an IL-17a antibody into the prefrontal cortex of ASD model mice and found that neutralizing IL-17a decreased the number of microglia and inhibited M1 polarization. Furthermore, neutralizing IL-17a improved social function in autism model mice.ConclusionOur study revealed that reduced neuroinflammation is an important mechanism of taVNS-mediated social improvement and neuroprotection against autism. This effect of taVNS could be attributed to the inhibition of the IL-17a pathway

Defining Key Genes Regulating Morphogenesis of Apocrine Sweat Gland in Sheepskin

The apocrine sweat gland is a unique skin appendage in humans compared to mouse and chicken models. The absence of apocrine sweat glands in chicken and murine skin largely restrains further understanding of the complexity of human skin biology and skin diseases, like hircismus. Sheep may serve as an additional system for skin appendage investigation owing to the distributions and histological similarities between the apocrine sweat glands of sheep trunk skin and human armpit skin. To understand the molecular mechanisms underlying morphogenesis of apocrine sweat glands in sheepskin, transcriptome analyses were conducted to reveal 1631 differentially expressed genes that were mainly enriched in three functional groups (cellular component, molecular function and biological process), particularly in gland, epithelial, hair follicle and skin development. There were 7 Gene Ontology (GO) terms enriched in epithelial cell migration and morphogenesis of branching epithelium that were potentially correlated with the wool follicle peg elongation. An additional 5 GO terms were enriched in gland morphogenesis (20 genes), gland development (42 genes), salivary gland morphogenesis and development (8 genes), branching involved in salivary gland morphogenesis (6 genes) and mammary gland epithelial cell differentiation (4 genes). The enriched gland-related genes and two Kyoto Encyclopedia of Genes and Genomes pathway genes (WNT and TGF-β) were potentially involved in the induction of apocrine sweat glands. Genes named BMPR1A, BMP7, SMAD4, TGFB3, WIF1, and WNT10B were selected to validate transcript expression by qRT-PCR. Immunohistochemistry was performed to localize markers for hair follicle (SOX2), skin fibroblast (PDGFRB), stem cells (SOX9) and BMP signaling (SMAD5) in sheepskin. SOX2 and PDGFRB were absent in apocrine sweat glands. SOX9 and SMAD5 were both observed in precursor cells of apocrine sweat glands and later in gland ducts. These results combined with the upregulation of BMP signaling genes indicate that apocrine sweat glands were originated from outer root sheath of primary wool follicle and positively regulated by BMP signaling. This report established the primary network regulating early development of apocrine sweat glands in sheepskin and will facilitate the further understanding of histology and pathology of apocrine sweat glands in human and companion animal skin

Acoustic Properties of Vowel Production in Mandarin-speaking Patients with Post-stroke Dysarthria

© 2018, The Author(s). This study investigated the acoustic features of vowel production in Mandarin-speaking patients with post-stroke dysarthria (PSD). The subjects included 31 native Mandarin-speaking patients with PSD (age: 25–83 years old) and 38 neurologically normal adults in a similar age range (age: 21–76 years old). Each subject was recorded producing a list of Mandarin monosyllables that included six monophthong vowels (i.e., /a, i, u, ɤ, y, o/) embedded in the /CV/ context. The patients’ speech samples were evaluated by two native Mandarin speakers. The evaluation scores were then used to classify all patients into two levels of severity: mild or moderate-to-severe. Formants (F1 and F2) were extracted from each vowel token. Results showed that all vowel categories in the patients with PSD were produced with more variability than in the healthy speakers. Great overlaps between vowel categories and reduced vowel space were observed in the patients. The magnitude of the vowel dispersion and overlap between vowel categories increased as a function of the severity of the disorder. The deviations of the vowel acoustic features in the patients in comparison to the healthy speakers may provide guidance for clinical rehabilitation to improve the speech intelligibility of patients with PSD

Breathers driven by polarization instabilities

Using an Er-doped fiber laser passively mode-locked fiber laser based on nonlinear polarization rotation (NPR) as a testbed, here we, for the first time, experimentally demonstrate the effect of the slow scale (thousands round-trip time) polarization instabilities on the emergence of breather-like spatiotemporal structures

Inverse correlation between vitamin D and C-reactive protein in newborns

Some studies suggested that adequate vitamin D might reduce inflammation in adults. However, little is known about this association in early life. We aimed to determine the relationship between cord blood 25-hydroxyvitamin D (25(OH)D) and C-reactive protein (CRP) in neonates. Cord blood levels of 25(OH)D and CRP were measured in 1491 neonates in Hefei, China. Potential confounders including maternal sociodemographic characteristics, perinatal health status, lifestyle, and birth outcomes were prospectively collected. The average values of cord blood 25(OH)D and CRP were 39.43 nmol/L (SD = 20.35) and 6.71 mg/L (SD = 3.07), respectively. Stratified by 25(OH)D levels, per 10 nmol/L increase in 25(OH)D, CRP decreased by 1.42 mg/L (95% CI: 0.90, 1.95) among neonates with 25(OH)D <25.0 nmol/L, and decreased by 0.49 mg/L (95% CI: 0.17, 0.80) among neonates with 25(OH)D between 25.0 nmol/L and 49.9 nmol/L, after adjusting for potential confounders. However, no significant association between 25(OH)D and CRP was observed among neonates with 25(OH)D ≥50 nmol/L. Cord blood 25(OH)D and CRP levels showed a significant seasonal trend with lower 25(OH)D and higher CRP during winter-spring than summer-autumn. Stratified by season, a significant linear association of 25(OH)D with CRP was observed in neonates born in winter-spring (adjusted β = −0.11, 95% CI: −0.13, −0.10), but not summer-autumn. Among neonates born in winter-spring, neonates with 25(OH)D <25 nmol/L had higher risk of CRP ≥10 mg/L (adjusted OR = 3.06, 95% CI: 2.00, 4.69), compared to neonates with 25(OH)D ≥25 nmol/L. Neonates with vitamin D deficiency had higher risk of exposure to elevated inflammation at birth

Quantitation of glutathione S-transferases in rice (Oryza sativa L.) roots exposed to cadmium by liquid chromatography–tandem mass spectrometry using isotope-labeled wing peptides as an internal standard

Abstract Background Plant glutathione S-transferases (GSTs, EC 2.5.1.18) are multifunctional enzymes involved in heavy metal cellular detoxification by conjugating the tripeptide (g-Glu-Cys-Gly) glutathione to heavy metals. Previous studies demonstrated that individual rice GSTs were differentially induced by heavy metal exposure at the mRNA transcript level. However, little information is available concerning changes in protein concentration of rice GSTs under heavy metal stress. Because the correlation between changes in protein concentration and gene expression under abiotic stress is poor, direct determination of rice GSTs protein concentrations during cadmium (Cd) exposure is a more effective and reliable approach to explore possible mechanisms of rice Cd translocation and accumulation. Results This study established an optimized and advanced liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based targeted proteomics assay for quantification of OsGSTF14 and OsGSTU6 proteins in Cd-stressed rice roots. The tryptic signature peptides were chosen as surrogate analytes and winged peptides containing the isotope-labeled signature peptides were used as the internal standards. The signature peptides exhibited good linearity in the range of 0.6–60 and 0.3–30 nM, respectively. The limit of detection and limit of quantification were 4.5 and 14.5 µg/g for OsGSTF14, respectively, and 2.1 and 7.0 µg/g for OsGSTU6. The spiking recoveries rates at low, medium and high levels were in the range of 72.5–93.4%, with intra- and inter-day precisions of 5.5–9.1 and 4.2–10.2%, respectively. Conclusions The assay successfully quantified the temporal and dose responses of OsGSTF14 and OsGSTU6 proteins in Cd-stressed rice roots, with good accuracy, precision and high-throughput. This assay will have significant application in developing quantification methods of other proteins in Cd-stressed rice, which may provide more insight into the mechanisms of Cd translocation and accumulation in rice

Development of Certified Reference Materials for the Determination of Apparent Amylose Content in Rice

Apparent amylose content (AAC) is one of the most important parameters in rice quality evaluation. In this study, four rice reference materials used to test rice AAC were developed. The AAC of rice reference materials were measured by a spectrophotometric method with a defatting procedure, calibrated from potato amylose and waxy rice amylopectin at the absorption wavelengths of 620 and 720 nm. Homogeneity test (n = 20) was judged by F-test based on the mean squares of among and within bottles, and short- and long-term stability monitoring was performed by T-test to check if there was significant degradation at the delivery temperature of under 40 &deg;C (14 days) and at 0&ndash;4 &deg;C storage condition (18 months), respectively. After joint evaluation by ten laboratories, Dixion and Cochran statistical analyses were presented. The expanded uncertainties were calculated based on the uncertainty of homogeneity, short- and long-term stability, and inter-laboratory validation containing factor k = 2. It found that the four reference materials were homogenous and stable, and had the AAC (g/100 g, k = 2) of 2.96 &plusmn; 1.01, 10.68 &plusmn; 0.66, 17.18 &plusmn; 1.04, and 16.09 &plusmn; 1.29, respectively, at 620 nm, and 1.46 &plusmn; 0.49, 10.44 &plusmn; 0.56, 16.82 &plusmn; 0.75, and 24.33 &plusmn; 0.52, respectively, at 720 nm. It was indicated that 720 nm was more suitable for the determination of rice AAC with lower uncertainties. The determinations of the AAC of 11 rice varieties were carried out by two methods, the method without defatting and with calibration from the four rice reference materials and the method with a defatting procedure and calibrating from potato amylose and waxy rice amylopectin. It confirmed that the undefatted rice reference materials could achieve satisfactory results to test the rice samples with the AAC ranging from 1 to 25 g/100 g. It would greatly reduce the time cost and improve testing efficiency and applicability, and provide technical support for the high-quality development of the rice industry

Dissipative soliton breathing dynamics driven by desynchronization of orthogonal polarization states

Breathing solitons, i.e., dynamic dissipative solitons with oscillating pulse shape and energy caused by different mechanisms of spatiotemporal instabilities, have received considerable interest from the aspects of nonlinear science and potential applications. However, by far, the study of breathing solitons is still limited within the time scale of hundreds of cavity round trips, which ignores the slow dynamics. To fill this lacuna, we theoretically investigate a new type of vector dissipative soliton breathing regime and experimentally demonstrate this concept using mode-locked fiber lasers, which arise from the desynchronization of orthogonal states of polarization (SOPs) in the form of complex oscillations of the phase difference between the states. The dynamic evolution of polarization states of the vector breathings solitons takes the form of a trajectory connecting two quasi-equilibrium orthogonal SOPs on the surface of the Poincaré sphere. The dwelling time near each state is on the scale of a tenth of a thousand cavity round trip times that equals the breathing period, which is up to 2 orders of magnitude longer than that for common breathers. The obtained results can reveal concepts in nonlinear science and may unlock approaches to the flexible manipulation of laser waveforms toward various applications in spectroscopy and metrology

Human hair follicle-derived mesenchymal stem cells promote tendon repair in a rabbit Achilles tendinopathy model

Abstract. Background:. Hair follicles are easily accessible and contain stem cells with different developmental origins, including mesenchymal stem cells (MSCs), that consequently reveal the potential of human hair follicle (hHF)-derived MSCs in repair and regeneration. However, the role of hHF-MSCs in Achilles tendinopathy (AT) remains unclear. The present study investigated the effects of hHF-MSCs on Achilles tendon repair in rabbits. Methods:. First, we extracted and characterized hHF-MSCs. Then, a rabbit tendinopathy model was constructed to analyze the ability of hHF-MSCs to promote repair in vivo. Anatomical observation and pathological and biomechanical analyses were performed to determine the effect of hHF-MSCs on AT, and quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical staining were performed to explore the molecular mechanisms through which hHF-MSCs affects AT. Furthermore, statistical analyses were performed using independent sample t test, one-way analysis of variance (ANOVA), and one-way repeated measures multivariate ANOVA as appropriate. Results:. Flow cytometry, a trilineage-induced differentiation test, confirmed that hHF-derived stem cells were derived from MSCs. The effect of hHF-MSCs on AT revealed that the Achilles tendon was anatomically healthy, as well as the maximum load carried by the Achilles tendon and hydroxyproline proteomic levels were increased. Moreover, collagen I and III were upregulated in rabbit AT treated with hHF-MSCs (compared with AT group; P < 0.05). Analysis of the molecular mechanisms revealed that hHF-MSCs promoted collagen fiber regeneration, possibly through Tenascin-C (TNC) upregulation and matrix metalloproteinase (MMP)-9 downregulation. Conclusions:. hHF-MSCs can be a treatment modality to promote AT repair in rabbits by upregulating collagen I and III. Further analysis revealed that treatment of AT using hHF-MSCs promoted the regeneration of collagen fiber, possibly because of upregulation of TNC and downregulation of MMP-9, thus suggesting that hHF-MSCs are more promising for AT

MOESM2 of Quantitation of glutathione S-transferases in rice (Oryza sativa L.) roots exposed to cadmium by liquid chromatography–tandem mass spectrometry using isotope-labeled wing peptides as an internal standard

Additional file 2. Comparison of protein concentrations extracted by minimum-step, TCA-acetone and phenol extraction protocols