bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast free-of-acrylamide clearing tissue (FACT)—an optimized new protocol for rapid, high-resolution imaging of three-dimensional brain tissue
Authors: Xu Na , Tamadon Amin , Liu Yaan , Ma Tong , Leak Rehana K. , Chen Jun , Gao Yanqin , Feng Yi
Published: August 2017

Fast Free-of-Acrylamide Clearing Tissue (FACT) is a new sodium dodecyl sulfate (SDS)-based clearing protocol for the chemical clearing and imaging of brain tissue containing transgenic or immunolabeled fluorescent proteins. In the present study, we have developed this new method and optimized multiple dimensions of the workflow, including reduced clearing time, improved efficiency of fluorescent signals without the need for electrophoretic or complex instrumentations, preservation of cytoarchitectural details, optimized confocal microscopy, and accelerated data collection. We systematically compared seven clearing protocols with the FACT protocol, using transgenic mouse brains with fluorochrome expression in microglia. Only six days were required for detecting transgene-labeled markers in a 1-mm thick brain slice from adult mice, and 14 days were required for detecting antibody-labeled markers in the same-sized tissue. Preservation of fluorescent signal was achieved by decreasing clearing time, adjusting the pH of the SDS solution, and using the appropriate temperature for tissue clearing, all of which contributed to the superiority of our method. We conclude that the FACT protocol can be successfully applied to the fluorescent imaging of mouse brain tissue, and will facilitate structural analyses and connectomics of large assemblies of cells and their networks in the context of three-dimensional organ systems.
Cesarean section without medical indication and risks of childhood allergic disorder, attenuated by breastfeeding
Authors: Chu Shuyuan , Zhang Yunting , Jiang Yanrui , Sun Wanqi , Zhu Qi , Wang Bin , Jiang Fan , Zhang Jun
Published: August 2017

Caesarean section (CS) may increase the risk of asthma and allergic diseases in children, but previous studies could not preclude the potential confounding effect of underlying medical indications for CS. We aim to assess the association between CS itself (without indications) and risks of asthma and allergic rhinitis in children. The 2014 Shanghai Children’s Health, Education and Lifestyle Evaluation was a large population-based survey with cluster random probability sampling in 26 primary schools in Shanghai, China, in 2014. The mode of delivery and child history of asthma and allergic rhinitis were reported by parents. We included 12639 children in our analysis. CS without medical indication was associated with an increased risk of childhood asthma. CS without medical indication and CS for fetal complications were associated with increased risks of childhood allergic rhinitis, respectively. In children fed by exclusive breastfeeding or mixed feeding in the first four months after birth, these risks were not significant. In contrast, in children fed by exclusive formula milk, CS was highly significantly associated with childhood asthma and allergic rhinitis. In conclusion, CS without medical indication was associated with increased risks of both childhood asthma and allergic rhinitis. Breastfeeding in early infancy may attenuate these risks.
Sleep problems and injury risk among juveniles: A systematic review and meta-analysis of observational studies
Authors: Wang Yun-Bing , Guo Zhen-Lang , Zhang Fan , Zhang Yong , Wang Shu-Sheng , Zhao Yong
Published: August 2017

Recent studies have reported inconsistent results regarding the association between sleep problems and injury risk among juveniles. Moreover, the extent of this risk remains largely unexplored. Thus, a systematic review and meta-analysis was conducted by our team to determine whether sleep problems increase the incidence of injuries among juveniles. PubMed, PsycINFO, Embase, and Cochrane Library databases were searched for relevant studies that explored the association between sleep problems and injury risk and have been published before July 2016. Multivariate adjusted odds ratio (OR) and associated 95% confidence intervals (CIs) were extracted and pooled using random-effects models. A total of 10 observational studies involving 73,418 participants were identified. Meta-analysis findings suggested that juveniles with sleep problems held a 1.64 times higher risk of injury than that of juveniles without sleep problems (OR: 1.64, 95% CI: 1.44–1.85). This relationship was also supported by subgroup analyses, which were based on different countries and study designs. The current evidence indicates that sleep problems are significantly associated with injury risk among juveniles. Sleep problems are highly important for young people; hence, sleep researchers and occupational physicians should focus on this aspect. Nevertheless, high-quality and adequately powered observational studies are still needed.
Microbial communities in marine sediments modify success of an invasive macrophyte
Authors: Gribben Paul E. , Nielsen Shaun , Seymour Justin R. , Bradley Daniel J. , West Matthew N. , Thomas Torsten
Published: August 2017

Invasive plants have extensive impacts on ecosystem function and biodiversity globally. Our inability to manage invasive species stems in part from a lack of understanding of the processes that control their successful establishment and spread. To date, studies have largely considered how above-ground processes control native/invasive plant interactions. Emerging research from terrestrial and wetland ecosystems demonstrates that below-ground processes under microbial control can determine the outcome of interactions between native and invasive plants. Whether sediment microbes modify the success of invasive macrophytes in marine ecosystems is untested, despite marine sediment microbes controlling many ecological processes (e.g. nutrient cycling) comparable to those in terrestrial ecosystems. We first show that sediment bacterial communities differ between the native seagrassZostera capricorniand the invasive algaCaulerpa taxifoliaand that those differences relate to functional changes in sulfur cycling between the macrophytes. Second, by experimentally manipulating the microbial communities we show that intact microbial communities inZ.capricornisediments provide biotic resistance by reducingC.taxifoliafragment growth 119% compared to when they are inactive, and intact microbial communities inC.taxifoliasediments have positive feedbacks by increasing fragment growth 200%. Thus, similar to terrestrial ecosystems, microorganisms appear to indirectly control the success of invasive macrophytes in marine ecosystems.
Enhanced Second Harmonic Generation by Mode Matching in Gain-assisted Double-plasmonic Resonance Nanostructure
Authors: Pan Gui-Ming , Yang Da-Jie , Zhou Li , Hao Zhong-Hua , Wang Qu-Quan
Published: August 2017

We theoretically study the gain-assisted double plasmonic resonances to enhance second harmonic generation (SHG) in a centrosymmetric multilayered silver-dielectric-gold-dielectric (SDGD) nanostructure. Introducing gain media into the dielectric layers can not only compensate the dissipation and lead to giant amplification of surface plasmons (SPs), but also excite local quadrupolar plasmon which can boost SHG by mode matching. Specifically, as the quadrupolar mode dominates SHG in our nanostructure, under the mode matching condition, the intensity of second harmonic near-field can be enhanced by 4.43 × 102 and 1.21 × 105 times when the super-resonance is matched only at the second harmonic (SH) frequency or fundamental frequency, respectively. Moreover, the intensity of SHG near-field is enhanced by as high as 6.55 × 107 times when the nanostructure is tuned to double super-resonances at both fundamental and SH frequencies. The findings in this work have potential applications in the design of nanosensors and nanolasers.
Targeted disruption of supraspinal motor circuitry reveals a distributed network underlying Restless Legs Syndrome (RLS)-like movements in the rat
Authors: Guo Chun-Ni , Yang Wen-Jia , Zhan Shi-Qin , Yang Xi-Fei , Chen Michael C. , Fuller Patrick M. , Lu Jun
Published: August 2017

In this study we uncovered, through targeted ablation, a potential role for corticospinal, cerebello-rubro-spinal, and hypothalamic A11 dopaminergic systems in the development of restless legs syndrome (RLS)-like movements during sleep. Targeted lesions in select basal ganglia (BG) structures also revealed a major role for nigrostriatal dopamine, the striatum, and the external globus pallidus (GPe) in regulating RLS-like movements, in particular pallidocortical projections from the GPe to the motor cortex. We further showed that pramipexiole, a dopamine agonist used to treat human RLS, reduced RLS-like movements. Taken together, our data show that BG-cortico-spinal, cerebello-rubro-spinal and A11 descending projections all contribute to the suppression of motor activity during sleep and sleep-wake transitions, and that disruption of these circuit nodes produces RLS-like movements. Taken together with findings from recent genomic studies in humans, our findings provide additional support for the concept that the anatomic and genetic etiological bases of RLS are diverse.
Quantitative proteome and phosphoproteome analyses highlight the adherent population during Trypanosoma cruzi metacyclogenesis
Authors: Amorim Juliana C. , Batista Michel , da Cunha Elizabeth S. , Lucena Aline C. R. , Lima Carla V. de Paula , Sousa Karla , Krieger Marco A. , Marchini Fabricio K.
Published: August 2017

Trypanosoma cruzi metacyclogenesis is a natural process that occurs inside the triatomine vector and corresponds to the differentiation of non-infective epimastigotes into infective metacyclic trypomastigotes. The biochemical alterations necessary for the differentiation process have been widely studied with a focus on adhesion and nutritional stress. Here, using a mass spectrometry approach, a large-scale phospho(proteome) study was performed with the aim of understanding the metacyclogenesis processes in a quantitative manner. The results indicate that major modulations in the phospho(proteome) occur under nutritional stress and after 12 and 24 h of adhesion. Significant changes involve key cellular processes, such as translation, oxidative stress, and the metabolism of macromolecules, including proteins, lipids, and carbohydrates. Analysis of the signalling triggered by kinases and phosphatases from 7,336 identified phosphorylation sites demonstrates that 260 of these sites are modulated throughout the differentiation process, and some of these modulated proteins have previously been identified as drug targets in trypanosomiasis treatment. To the best of our knowledge, this study provides the first quantitative results highlighting the modulation of phosphorylation sites during metacyclogenesis and the greater coverage of the proteome to the parasite during this process. The data are available via ProteomeXchange with identifier number PXD006171.
Lipidomic Signatures of Nonhuman Primates with Radiation-Induced Hematopoietic Syndrome
Authors: Pannkuk Evan L. , Laiakis Evagelia C. , Singh Vijay K. , Fornace Albert J.
Published: August 2017

Concern over potential exposures of ionizing radiation (IR) to large populations has emphasized the need for rapid and reliable methods of biodosimetry to determine absorbed dose and required triage. Lipidomics has emerged as a powerful technique for large-scale lipid identification and quantification. Indirect effects from IR exposure generate reactive oxygen species (ROS) through water hydrolysis and may subsequently damage cellular lipids. Thus, rapid identification of specific affected lipid molecules represents possible targets for biodosimetry. The current study addresses temporal changes in the serum lipidome from 4 h to 28 d in nonhuman primates (NHPs) with radiation-induced hematopoietic syndrome (6.5 Gy exposure, LD50/60). Statistical analyses revealed a highly dynamic temporal response in the serum lipidome after IR exposure. Marked lipidomic perturbations occurred within 24 h post-irradiation along with increases in cytokine levels and C-reactive protein. Decreases were observed in di- and triacylglycerides, sphingomyelins (SMs), lysophosphatidylcholines (LysoPCs), and esterified sterols. Conversely, free fatty acids and monoacylglycerides significantly increased. Decreased levels of SMs and increased levels of LysoPCs may be important markers for biodosimetry ~2 d–3 d post-irradiation. The biphasic and dynamic response to the serum lipidome post-irradiation emphasize the importance of determining the temporal long-term response of possible radiation markers.
A multi-trap microfluidic chip enabling longitudinal studies of nerve regeneration in Caenorhabditis elegans
Authors: Gokce Sertan Kutal , Hegarty Evan Marley , Mondal Sudip , Zhao Peisen , Ghorashian Navid , Hilliard Massimo A. , Ben-Yakar Adela
Published: August 2017

Several sophisticated microfluidic devices have recently been proposed for femtosecond laser axotomy in the nematode C. elegans for immobilization of the animals for surgery to overcome time-consuming and labor-intensive manual processes. However, nerve regeneration studies require long-term recovery of the animals and multiple imaging sessions to observe the regeneration capabilities of their axons post-injury. Here we present a simple, multi-trap device, consisting of a single PDMS (polydimethylsiloxane) layer, which can immobilize up to 20 animals at the favorable orientation for optical access needed for precise laser surgery and high-resolution imaging. The new device, named “worm hospital” allows us to perform the entire nerve regeneration studies, including on-chip axotomy, post-surgery housing for recovery, and post-recovery imaging all on one microfluidic chip. Utilizing the worm hospital and analysis of mutants, we observed that most but not all neurodevelopmental genes in the Wnt/Frizzled pathway are important for regeneration of the two touch receptor neurons ALM and PLM. Using our new chip, we observed that the cwn-2 and cfz-2 mutations significantly reduced the reconnection possibilities of both neurons without any significant reduction in the regrowth lengths of the severed axons. We observed a similar regeneration phenotype with cwn-1 mutation in ALM neurons only.
Identification of butenolide regulatory system controlling secondary metabolism in Streptomyces albus J1074
Authors: Ahmed Yousra , Rebets Yuriy , Tokovenko Bogdan , Brötz Elke , Luzhetskyy Andriy
Published: August 2017

A large majority of genome-encrypted chemical diversity in actinobacteria remains to be discovered, which is related to the low level of secondary metabolism genes expression. Here, we report the application of a reporter-guided screening strategy to activate cryptic polycyclic tetramate macrolactam gene clusters in Streptomyces albus J1074. The analysis of the S. albus transcriptome revealed an overall low level of secondary metabolism genes transcription. Combined with transposon mutagenesis, reporter-guided screening resulted in the selection of two S. albus strains with altered secondary metabolites production. Transposon insertion in the most prominent strain, S. albus ATGSal2P2::TN14, was mapped to the XNR_3174 gene encoding an unclassified transcriptional regulator. The mutant strain was found to produce the avenolide-like compound butenolide 4. The deletion of the gene encoding a putative acyl-CoA oxidase, an orthologue of the Streptomyces avermitilis avenolide biosynthesis enzyme, in the S. albus XNR_3174 mutant caused silencing of secondary metabolism. The homologues of XNR_3174 and the butenolide biosynthesis genes were found in the genomes of multiple Streptomyces species. This result leads us to believe that the discovered regulatory elements comprise a new condition-dependent system that controls secondary metabolism in actinobacteria and can be manipulated to activate cryptic biosynthetic pathways.
A kinetic model of multiple phenotypic states for breast cancer cells
Authors: Qiu Kang , Gao Kai-fu , Yang Li-jian , Zhang Zhao-kang , Wang Ran , Ma Hui-shu , Jia Ya
Published: August 2017

Quantitative modeling of microscopic genes regulatory mechanisms in an individual cell is a crucial step towards understanding various macroscopic physiological phenomena of cell populations. Based on the regulatory mechanisms of genes zeb1 and cdh1 in the growth and development of breast cancer cells, we propose a kinetic model at the level of single cell. By constructing the effective landscape of underlying stationary probability for the genes expressions, it is found that (i) each breast cancer cell has three phenotypic states (i.e., the stem-like, basal, and luminal states) which correspond to three attractions of the probability landscape. (ii) The interconversions between phenotypic states can be induced by the noise intensity and the property of phenotypic switching is quantified by the mean first-passage time. (iii) Under certain conditions, the probabilities of each cancer cell appearing in the three states are consistent with the macroscopic phenotypic equilibrium proportions in the breast cancer SUM159 cell line. (iv) Our kinetic model involving the TGF-β signal can also qualitatively explain several macroscopic physiological phenomena of breast cancer cells, such as the “TGF-β paradox” in tumor therapy, the five clinical subtypes of breast cancer cells, and the effects of transient TGF-β on breast cancer metastasis.
Automated Classification of Benign and Malignant Proliferative Breast Lesions
Authors: Radiya-Dixit Evani , Zhu David , Beck Andrew H.
Published: August 2017

Misclassification of breast lesions can result in either cancer progression or unnecessary chemotherapy. Automated classification tools are seen as promising second opinion providers in reducing such errors. We have developed predictive algorithms that automate the categorization of breast lesions as either benign usual ductal hyperplasia (UDH) or malignant ductal carcinoma in situ (DCIS). From diagnosed breast biopsy images from two hospitals, we obtained 392 biomarkers using Dong et al.’s (2014) computational tools for nuclei identification and feature extraction. We implemented six machine learning models and enhanced them by reducing prediction variance, extracting active features, and combining multiple algorithms. We used the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for performance evaluation. Our top-performing model, a Combined model with Active Feature Extraction (CAFE) consisting of two logistic regression algorithms, obtained an AUC of 0.918 when trained on data from one hospital and tested on samples of the other, a statistically significant improvement over Dong et al.’s AUC of 0.858. Pathologists can substantially improve their diagnoses by using it as an unbiased validator. In the future, our work can also serve as a valuable methodology for differentiating between low-grade and high-grade DCIS.
A functional approach to the structural complexity of coral assemblages based on colony morphological features
Authors: Denis Vianney , Ribas-Deulofeu Lauriane , Sturaro Nicolas , Kuo Chao-Yang , Chen Chaolun Allen
Published: August 2017

Colony morphological features is among the best predictor of the scleractinian coral’s function in reef ecosystems. However, morphological traits are categorical and to convert this information into a quantitative value as well as estimate their influence on ecosystem process remain a challenge. Here, we propose a trait-based approach to quantify morphological diversity and assess the structural complexity of the habitat provided by corals. We used a previously published dataset that is related to a bleaching event that affected the coral reef off Tikus Island in Indonesia in 1983. We found clear signs of recovery of the coral assemblage’s complexity toward pre El Niño conditions five years after the event. Independent of the change observed in species richness, this return in structural complexity was accompanied by a global decrease in species number associated with each particular morphological entity (Functional Redundancy) and an increase in the number of single-species entities (Functional Vulnerability). Together with species loss, we show an overall functional erosion of the coral assemblage and suggest that the role of the coral reef habitat could be strongly imperiled under repeated or synergistic disturbances. This approach offers an opportunity for a better understanding of coral responses to natural and anthropogenic disturbances.
IRF2BP2-deficient microglia block the anxiolytic effect of enhanced postnatal care
Authors: Hari Aswin , Cruz Shelly A. , Qin Zhaohong , Couture Pascal , Vilmundarson Ragnar O. , Huang Hua , Stewart Alexandre F. R. , Chen Hsiao-Huei
Published: August 2017

Enhanced postnatal care (EPC) increases resilience to adversity in adulthood. Since microglia participate in shaping neural circuits, we asked how ablation of an inflammation-suppressing factor IRF2BP2 (Interferon Regulatory Factor 2 Binding Protein 2) in microglia would affect the responses to EPC. Mice lacking IRF2BP2 in microglia (KO) and littermate controls (WT) were subjected to EPC during the first 3 weeks after birth. EPC reduced anxiety in WT but not KO mice. This was associated with reduced inflammatory cytokine expression in the hypothalamus. Whole genome RNAseq profiling of the hypothalamus identified 101 genes whose expression was altered by EPC: 95 in WT, 11 in KO, with 5 in common that changed in opposite directions. Proteoglycan 4 (Prg4), prostaglandin D2 synthase (Ptgds) and extracellular matrix protease inhibitor Itih2 were suppressed by EPC in WT but elevated in KO mice. On the other hand, the glutamate transporter VGLUT1 (Slc17a7) was increased by EPC in WT but not KO mice. Prostaglandin D2 (PGD2) is known to enhance microglial inflammation and promote Gfap expression. ELISA confirmed reduced PGD2 in the hypothalamus of WT mice after EPC, associated with reduced Gfap expression. Our study suggests that the anxiety-reducing effect of EPC operates by suppressing microglial inflammation, likely by reducing neuronal prostaglandin D2 production.
Identification of the protective mechanisms of Lactoferrin in the irradiated salivary gland
Authors: Sakai Manabu , Matsushita Takumi , Hoshino Ryoko , Ono Hitomi , Ikai Kazuki , Sakai Takayoshi
Published: August 2017

Radiotherapy is commonly used in patients with head and neck cancer, and usually results in irreversible salivary glands damage and hypofunction. It is therefore important to manage such irradiation to prevent damage to the salivary glands. A previous study showed that Lactoferrin (LF) has a radioprotective effect, but the mechanism was not determined in salivary glands. In the present study, we investigated the detailed radioprotective effect of LF using bothex vivosubmandibular salivary gland organ culture and ICR male micein vivo. We found that LF had effects on both cell proliferation and CyclinD1-mediated cell-cycle progression which were regulated via the ERK1/2 and AKT signal transduction pathways. In addition, LF affected acinar cell structure and function after irradiation. These findings suggest that LF may be a useful agent to prevent irradiation effects in salivary glands.
Water-assisted and controllable synthesis of core/shell/shell structured carbon-based nanohybrids, and their magnetic and microwave absorption properties
Authors: Qi Xiaosi , Yang Erqi , Cai Hongbo , Xie Ren , Bai Zhongchen , Jiang Yang , Qin Shuijie , Zhong Wei , Du Youwei
Published: August 2017

By controlling the pyrolysis temperature, core/shell/shell structured Fe/Fe5C2/carbon nanotube bundles (Fe/Fe5C2/CNTBs), Fe/Fe3C/helical carbon nanotubes (Fe/Fe3C/HCNTs) and Fe/Fe3C/chain-like carbon nanospheres (Fe/Fe3C/CCNSs) with high encapsulation efficiency could be selectively synthesized in large-scale by water-assisted chemical vapor deposition method. Water vapor was proved to play an important role in the growth process. Because of α-Fe nanoparticles tightly wrapped by two layers, the obtained core/shell/shell structured nanohybrids showed high stabilities and good magnetic properties. The minimum reflection loss values of the as-prepared nanohybrids reached approximately −15.0, −46.3 and −37.1 dB, respectively. The excellent microwave absorption properties of the as-prepared core/shell/shell structured nanohybrids were considered to the quarter-wavelength matching model. Moreover, the possible enhanced microwave absorption mechanism of the as-prepared Fe/Fe3C/HCNTs and Fe/Fe3C/CCNSs were discussed in details. Therefore, we proposed a simple, inexpensive and environment-benign strategy for the synthesis of core/shell/shell structured carbon-based nanohybrids, exhibiting a promising prospect as high performance microwave absorbing materials.
Integrative Approach with Electrophysiological and Theoretical Methods Reveals a New Role of S4 Positively Charged Residues in PKD2L1 Channel Voltage-Sensing
Authors: Numata Tomohiro , Tsumoto Kunichika , Yamada Kazunori , Kurokawa Tatsuki , Hirose Shinichi , Nomura Hideki , Kawano Mitsuhiro , Kurachi Yoshihisa , Inoue Ryuji , Mori Yasuo
Published: August 2017

Numerical model-based simulations provide important insights into ion channel gating when experimental limitations exist. Here, a novel strategy combining numerical simulations with patch clamp experiments was used to investigate the net positive charges in the putative transmembrane segment 4 (S4) of the atypical, positively-shifted voltage-dependence of polycystic kidney disease 2-like 1 (PKD2L1) channel. Charge-neutralising mutations (K452Q, K455Q and K461Q) in S4 reduced gating charges, positively shifted the Boltzmann-type activation curve [i.e., open probability (Popen)-V curve] and altered the time-courses of activation/deactivation of PKD2L1, indicating that this region constitutes part of a voltage sensor. Numerical reconstruction of wild-type (WT) and mutant PKD2L1-mediated currents necessitated, besides their voltage-dependent gating parameters, a scaling factor that describes the voltage-dependence of maximal conductance, Gmax. Subsequent single-channel conductance (γ) measurements revealed that voltage-dependence of Gmax in WT can be explained by the inward-rectifying property of γ, which is greatly changed in PKD2L1 mutants. Homology modelling based on PKD2 and NaVAb structures suggest that such voltage dependence of Popen and γ in PKD2L1 could both reflect the charged state of the S4 domain. The present conjunctive experimental and theoretical approaches provide a framework to explore the undetermined mechanism(s) regulating TRP channels that possess non-classical voltage-dependent properties.
High predictive values of RBC membrane-based diagnostics by biophotonics in an integrated approach for Autism Spectrum Disorders
Authors: Giacometti Giorgia , Ferreri Carla , Sansone Anna , Chatgilialoglu Chryssostomos , Marzetti Carla , Spyratou Ellas , Georgakilas Alexandros G. , Marini Marina , Abruzzo Provvidenza M. , Bolotta Alessandra , Ghezzo Alessandro , Minguzzi Renato , Posar Annio , Visconti Paola
Published: August 2017

Membranes attract attention in medicine, concerning lipidome composition and fatty acid correlation with neurological diseases. Hyperspectral dark field microscopy (HDFM), a biophotonic imaging using reflectance spectra, provides accurate characterization of healthy adult RBC identifying a library of 8 spectral end-members. Here we report hyperspectral RBC imaging in children affected by Autism Spectrum Disorder (ASD) (n = 21) compared to healthy age-matched subjects (n = 20), investigating if statistically significant differences in their HDFM spectra exist, that can comprehensively map a membrane impairment involved in disease. A significant difference concerning one end-member (spectrum 4) was found (P value = 0.0021). A thorough statistical treatment evidenced: i) diagnostic performance by the receiving operators curve (ROC) analysis, with cut-offs and very high predictive values (P value = 0.0008) of spectrum 4 for identifying disease; ii) significant correlations of spectrum 4 with clinical parameters and with the RBC membrane deficit of the omega-3 docosahexaenoic acid (DHA) in ASD patients; iii) by principal component analysis, very high affinity values of spectrum 4 to the factor that combines behavioural parameters and the variable “cc” discriminating cases and controls. These results foresee the use of biophotonic methodologies in ASD diagnostic panels combining with molecular elements for a correct neuronal growth.
An Orbital Angular Momentum (OAM) Mode Reconfigurable Antenna for Channel Capacity Improvement and Digital Data Encoding
Authors: Liu Baiyang , Lin Guoying , Cui Yuehui , Li RongLin
Published: August 2017

For purpose of utilizing orbital angular momentum (OAM) mode diversity, multiple OAM beams should be generated preferably by a single antenna. In this paper, an OAM mode reconfigurable antenna is proposed. Different from the existed OAM antennas with multiple ports for multiple OAM modes transmitting, the proposed antenna with only a single port, but it can be used to transmit mode 1 or mode −1 OAM beams arbitrary by controlling the PIN diodes on the feeding network through a programmable microcontroller which control by a remote controller. Simulation and measurement results such as return loss, near-field and far-field radiation patterns of two operating states for mode 1 and mode −1, and OAM mode orthogonality are given. The proposed antenna can serve as a candidate for utilizing OAM diversity, namely phase diversity to increase channel capacity at 2.4 GHz. Moreover, an OAM-mode based encoding method is experimentally carried out by the proposed OAM mode reconfigurable antenna, the digital data are encoded and decoded by different OAM modes. At the transmitter, the proposed OAM mode reconfigurable antenna is used to encode the digital data, data symbol 0 and 1 are mapped to OAM mode 1 and mode −1, respectively. At the receiver, the data symbols are decoded by phase gradient method.
Decrease of FSTL1-BMP4-Smad signaling predicts poor prognosis in lung adenocarcinoma but not in squamous cell carcinoma
Authors: Chiou Jean , Su Chia-Yi , Jan Yi-Hua , Yang Chih-Jen , Huang Ming-Shyan , Yu Yung-Luen , Hsiao Michael
Published: August 2017

Follistatin-related protein 1 (FSTL1) plays a critical role in lung development through regulating BMP4-p-Smad1/5/8-Smad4 pathway. Regarding that many developmental pathways in embryogenesis are dysregulated in cancer, we aim to unravel the role of FSTL1-BMP4-Smad pathway in lung cancer. Our results showed low FSTL1 immunoexpression was significantly correlated with poor prognosis while patients with low BMP4 or low Smad4 immunoexpression showed a trend toward poor prognosis. When stratified by different histological types, low FSTL1, BMP4, and Smad4 expression retained their trends in predicting poor prognosis in lung adenocarcinoma (LUAD) but not in lung squamous cell carcinoma (SCC). Low FSTL1, BMP4, and Smad4 expression were more frequently observed in LUAD patients with smoking history. To determine smoking effect on FSTL1, normal cell BEAS2B and lung cancer cell lines was treated with nicotine and the results showed nicotine increased the proliferation of these cells. Interestingly, FSTL1 attenuated nicotine-induced BEAS2B and lung cancer cell line proliferation. Altogether, low FSTL1, BMP4, and Smad4 expression significantly correlated with poor prognosis in LUAD but not in SCC. Frequent decrease of FSTL1 expression in smokers LUAD further indicates its importance and therapeutic potential for lung cancer patients with specific subtypes. FSTL1 may prevent nicotine-induced lung cancer cell proliferation.
The Role of Na+/Ca2+ Exchanger 1 in Maintaining Ductus Arteriosus Patency
Authors: Li Minghui , Jiang Chuan , Ye Lincai , Wang Shoubao , Zhang Haibo , Liu Jinfen , Hong Haifa
Published: August 2017

Patency of the ductus arteriosus (DA) is crucial for both fetal circulation and patients with DA-dependent congenital heart diseases (CHD). The Na+/Ca2+ exchanger 1 (NCX1) protein has been shown to play a key role in the regulation of vascular tone and is elevated in DA-dependent CHD. This current study was conducted to investigate the mechanisms underpinning the role of NCX1 in DA patency. Our data showed NCX1 expression was up-regulated in the DA of fetal mice. Up-regulation of NCX1 expression resulted in a concomitant decrease in cytosolic Ca2+ levels in human DA smooth muscle cells (DASMCs) and an inhibition of the proliferation and migration capacities of human DASMCs. Furthermore, treatment of DASMCs with KB-R7943, which can reduce Ca2+ influx, resulted in the inhibition of both cell proliferation and migration. These findings indicate that NCX1 may play a role in maintaining patent DA not only by preventing DA functional closure through reducing cytosolic Ca2+ level in DASMC but also by delaying the anatomical closure process. The latter delay is facilitated by the down-regulation of human DASMC proliferation and migration. It is also likely that a reduction in cytosolic Ca2+ levels inhibits the proliferation and migration capacities of human DASMCs in vitro.
Early gestational maternal low-protein diet diminishes hepatic response to fasting in young adult male mice
Authors: Sato Noriko , Sudo Katsuko , Mori Masayo , Imai Chihiro , Muramatsu Masaaki , Sugimoto Masahiro
Published: August 2017

Maternal low-protein (MLP) diet can lead to hepatic steatosis, which only develops with ageing. It is still unclear whether the young offspring show any signs of past exposure to prenatal adverse conditions. We hypothesized that early nutritional insult would first affect the dynamic responsiveness to nutritional challenges rather than the static state. We analyzed the transcriptome and metabolome profiles of the hepatic response to fasting/refeeding in young male mice offspring to identify changes induced by early gestational MLP diet. Restricted MLP exposure strictly to early gestation was achieved by the embryo transfer method. As a result, the fasting-induced upregulation of genes related to long-chain fatty acid metabolism and of stress response genes related to protein folding were significantly diminished in MLP pups. Lipid profiling after fasting showed that the hepatic signature of triacylglycerols was shifted to longer acyl-chains and higher saturation by the MLP diet. Bioinformatic analyses suggested that these phenomenological changes may be partially linked to the peroxisome proliferator activated receptor α (PPARα) pathway. Taken together, early gestational MLP diet affected the hepatic dynamic response to nutritional stress in seemingly healthy young offspring, accompanied with partial deterioration of PPARα action.
Production of Monoclonal Antibodies to Pathologic β-sheet Oligomeric Conformers in Neurodegenerative Diseases
Authors: Goñi Fernando , Martá-Ariza Mitchell , Peyser Daniel , Herline Krystal , Wisniewski Thomas
Published: August 2017

We describe a novel approach to produce conformational monoclonal antibodies selected to specifically react with the β-sheet secondary structure of pathological oligomeric conformers, characteristic of many neurodegenerative diseases. Contrary to past and current efforts, we utilize a mammalian non-self-antigen as an immunogen. The small, non-self peptide selected was covalently polymerized with glutaraldehyde until it reached a high β-sheet secondary structure content, and species between 10–100kDa that are immunogenic, stable and soluble (p13Bri). Inoculation of p13Bri in mice elicited antibodies to the peptide and the β-sheet secondary structure conformation. Hybridomas were produced and clones selected for their reactivity with at least two different oligomeric conformers from Alzheimer’s, Parkinson and/or Prion diseases. The resulting conformational monoclonals are able to detect pathological oligomeric forms in different human neurodegenerative diseases by ELISA, immunohistochemistry and immunoblots. This technological approach may be useful to develop tools for detection, monitoring and treatment of multiple misfolding disorders.
Expression and Purification of the Pain Receptor TRPV1 for Spectroscopic Analysis
Authors: Velisetty Phanindra , Stein Richard A. , Sierra-Valdez Francisco J. , Vásquez Valeria , Cordero-Morales Julio F.
Published: August 2017

The transient receptor potential vanilloid 1 (TRPV1) channel is an essential component of the cellular mechanism through which noxious stimuli evoke pain. Functional and structural characterizations of TRPV1 shed light on vanilloid activation, yet the mechanisms for temperature and proton gating remain largely unknown. Spectroscopic approaches are needed to understand the mechanisms by which TRPV1 translates diverse stimuli into channel opening. Here, we have engineered a minimal cysteine-less rat TRPV1 construct (eTRPV1) that can be stably purified and reconstituted for spectroscopic studies. Biophysical analyses of TRPV1 constructs reveal that the S5-pore helix loop influences protein stability and vanilloid and proton responses, but not thermal sensitivity. Cysteine mutants retain function and stability for double electron-electron resonance (DEER) and electron paramagnetic resonance (EPR) spectroscopies. DEER measurements in the closed state demonstrate that eTRPV1 reports distances in the extracellular vestibule, equivalent to those observed in the apo TRPV1 structure. EPR measurements show a distinct pattern of mobilities and spectral features, in detergent and liposomes, for residues at the pore domain that agree with their location in the TRPV1 structure. Our results set the stage for a systematic characterization of TRPV1 using spectroscopic approaches to reveal conformational changes compatible with thermal- and ligand-dependent gating.
Loss of the podocyte glucocorticoid receptor exacerbates proteinuria after injury
Authors: Zhou Han , Tian Xuefei , Tufro Alda , Moeckel Gilbert , Ishibe Shuta , Goodwin Julie
Published: August 2017

Nephrotic syndrome is a common disorder in adults and children whose etiology is largely unknown. Glucocorticoids remain the mainstay of therapy in most cases, though their mechanism of action remains poorly understood. Emerging evidence suggests that immunomodulatory therapies used in nephrotic syndrome directly target the podocytes. To study how steroids directly affect the podocytes in the treatment of proteinuria, we created a mouse model with podocyte-specific deletion of the glucocorticoid receptor. The podocyte-specific glucocorticoid receptor (GR) knockout mice had similar renal function and protein excretion compared to wild type. However, after glomerular injury induced by either LPS or nephrotoxic serum, the podocyte GR knockout mice demonstrated worsened proteinuria compared to wild type. Ultrastructural examination of podocytes confirmed more robust foot process effacement in the knockout animals. Expression of several key slit diaphragm protein was down regulated in pGR KO mice. Primary podocytes isolated from wild type and podocyte GR knockout mice showed similar actin stress fiber staining patterns in unstimulated conditions. Yet, when exposed to LPS, GR knockout podocytes demonstrated fewer stress fibers and impaired migration compared to wild type podocytes. We conclude that the podocyte glucocorticoid receptor is important for limiting proteinuria in settings of podocyte injury.
Highly tunable time-reversal-invariant topological superconductivity in topological insulator thin films
Authors: Parhizgar Fariborz , Black-Schaffer Annica M.
Published: August 2017

We study time-reversal-invariant topological superconductivity in topological insulator (TI) thin films including both intra- and inter-surface pairing. We find a nontrivial topology for multiple different configurations. For intra-surface pairing a π-phase difference between the intra-surface pairing states is required. We show that in this case the resulting topological phase is highly tunable by both an applied electric field and varied chemical potential. For spin-singlet inter-surface pairing, a sign-changing tunnel coupling present in many TI thin films is needed, and again, the topology can be tuned by electric field or doping. Notably, we find that the required inter-surface pairing strength for achieving nontrivial topology can still be subdominant compared to the intra-surface pairing. Finally, for spin-triplet inter-surface pairing we prove that the superconducting state is always topological nontrivial. We show that thin films of Cu-doped Bi2Se3 will likely host such spin-triplet inter-surface pairing. Taken together, these results show that time-reversal-invariant topological superconductivity is common in superconducting TI thin films and that the topological phase and its Kramers pair of Majorana edge modes is highly tunable with an applied electric field and varied chemical potential.
An approximate analytical solution of the Bethe equation for charged particles in the radiotherapeutic energy range
Authors: Grimes David Robert , Warren Daniel R. , Partridge Mike
Published: August 2017

Charged particles such as protons and carbon ions are an increasingly important tool in radiotherapy. There are however unresolved physics issues impeding optimal implementation, including estimation of dose deposition in non-homogeneous tissue, an essential aspect of treatment optimization. Monte Carlo (MC) methods can be employed to estimate radiation profile, and whilst powerful, these are computationally expensive, limiting practicality. In this work, we start from fundamental physics in the form of the Bethe equation to yield a novel approximate analytical solution for particle range, energy and linear energy transfer (LET). The solution is given in terms of the exponential integral function with relativistic co-ordinate transform, allowing application at radiotherapeutic energy levels (50–350 MeV protons, 100–600 Mev/a.m.u carbon ions). Model results agreed closely for protons and carbon-ions (mean error within ≈1%) of literature values. Agreement was high along particle track, with some discrepancy manifesting at track-end. The model presented has applications within a charged particle radiotherapy optimization framework as a rapid method for dose and LET estimation, capable of accounting for heterogeneity in electron density and ionization potential.
The relationship between scleral staphyloma and choroidal thinning in highly myopic eyes: The Beijing Eye Study
Authors: Zhou Ling Xiao , Shao Lei , Xu Liang , Wei Wen Bin , Wang Ya Xing , You Qi Sheng
Published: August 2017

Based on the Beijing Eye Study 2011, a detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging for measurement of subfoveal choroidal thickness (SFCT) and relative height of posterior scleral staphyloma. OCT images were obtained in 103 highly myopic eyes (≤−6.00 diopters) and 227 normal eyes. The mean SFCT in highly myopic eyes was 110.6 ± 85.2 μm (range, 3 to 395 μm). The SFCT of high myopia without posterior scleral staphyloma(55 eyes) was 157.79 ± 85.18 μm, which was significantly greater than that (54.94 ± 49.96 μm) of high myopia with posterior scleral staphyloma (48 eyes) (P < 0.001). In multivariate analysis, posterior scleral staphyloma was the most important factor of choroidal thinning in high myopia (F = 22.63; P < 0.001), then age (F = 19.14; P < 0.001), axial length (F = 17.37; P < 0.001) and gender (F = 17.31; P < 0.001). The SFCT in highly myopic eyes is very thin and undergoes further thinning with increasing age and axial length (refractive error). Posterior staphyloma formation was a key factor in choroidal thinning in highly myopic eyes and to be a good indicator for risk management of choroidal thinning. Abnormalities of the choroid may play a role in the pathogenesis of myopic degeneration.
White Light Emission from Fluorescent SiC with Porous Surface
Authors: Lu Weifang , Ou Yiyu , Fiordaliso Elisabetta Maria , Iwasa Yoshimi , Jokubavicius Valdas , Syväjärvi Mikael , Kamiyama Satoshi , Petersen Paul Michael , Ou Haiyan
Published: August 2017

Abstarct

We report for the first time a NUV light to white light conversion in a N-B co-doped 6H-SiC (fluorescent SiC) layer containing a hybrid structure. The surface of fluorescent SiC sample contains porous structures fabricated by anodic oxidation method. After passivation by 20 nm thick Al2O3, the photoluminescence intensity from the porous layer was significant enhanced by a factor of more than 12. Using a porous layer of moderate thickness (~10 µm), high-quality white light emission was realized by combining the independent emissions of blue-green emission from the porous layer and yellow emission from the bulk fluorescent SiC layer. A high color rendering index of 81.1 has been achieved. Photoluminescence spectra in porous layers fabricated in both commercial n-type and lab grown N-B co-doped 6H-SiC show two emission peaks centered approximately at 460 nm and 530 nm. Such blue-green emission phenomenon can be attributed to neutral oxygen vacancies and interface C-related surface defects generated dring anodic oxidation process. Porous fluorescent SiC can offer a great flexibility in color rendering by changing the thickness of porous layer and bulk fluorescent layer. Such a novel approach opens a new perspective for the development of high performance and rare-earth element free white light emitting materials.
FTIR-spectroscopic and LA-ICP-MS imaging for combined hyperspectral image analysis of tumor models
Authors: Balbekova A. , Bonta M. , Török S. , Ofner J. , Döme B. , Limbeck A. , Lendl B.
Published: August 2017

Advantages of combined image analysis were demonstrated using infrared spectroscopy and mass spectrometry while characterizing biochemical changes occurring in tumor models.
Selective separation of xanthones and saponins from the rhizomes of Anemarrhena asphodeloides by modulating the density of surface charges in C18-bonded stationary phases
Authors: Cai Jianfeng , Xin Huaxia , Cheng Lingping , Guo Zhimou , Feng Jiatao , Fu Qing , Jin Yu , Liang Xinmiao
Published: August 2017

A rapid and robust separation method based on the positively charged reversed-phase (PGRP) stationary phase was developed for selective separation of saponins and xanthones from the rhizomes of Anemarrhena asphodeloides.
Palladium–gold single atom alloy catalysts for liquid phase selective hydrogenation of 1-hexyne
Authors: Liu Jilei , Shan Junjun , Lucci Felicia R. , Cao Sufeng , Sykes E. Charles H. , Flytzani-Stephanopoulos Maria
Published: August 2017

Silica supported and unsupported PdAu single atom alloys (SAAs) were investigated for the selective hydrogenation of 1-hexyne to hexenes under mild conditions.
Chelated [Zn(cyclam)]2+Lewis acid improves the reactivity of the electrochemical reduction of CO2by Mn catalysts with bulky bipyridine ligands
Authors: Zhanaidarova Almagul , Steger Han , Reineke Mark H. , Kubiak Clifford. P.
Published: August 2017

This communication reports the use of a soluble Lewis acid complex, [Zn(cyclam)]2+(cyclam = 1,4,8,11-tetraazacyclotetradecane) as a co-catalyst coupled with Mn(Mesbpy)(CO)3Br (Mesbpy = 6,6′-dimesityl-2,2′-bipyridine) for the electrochemical reduction of CO2to CO.
Nickel-catalysed direct C2-arylation of N-heterocyclic carbenes
Authors: Ho Nga Kim T. , Neumann Beate , Stammler Hans-Georg , Menezes da Silva Vitor H. , Watanabe Daniel G. , Braga Ataualpa A. C. , Ghadwal Rajendra S.
Published: August 2017

Direct C2-arylation of NHCs to C2-arylated imidazolium salts (III) is achieved using Ni-catalysis. The dinuclear Ni(i) species I undergoes oxidative addition with ArX to give the Ni(ii) intermediate II. Reductive elimination delivers the arylation product III and regenerates the catalyst I.
Scaffold-reinforced perovskite compound solar cells
Authors: Watson Brian L. , Rolston Nicholas , Printz Adam D. , Dauskardt Reinhold H.
Published: August 2017

The relative insensitivity of the optoelectronic properties of organometal trihalide perovskites to crystallographic defects and impurities has enabled fabrication of highly-efficient perovskite solar cells by scalable solution-state deposition techniques well suited to low-cost manufacturing.