bluuebunny/crossref_metadata_2025 huggingface dataset:
The Resuscitative and Pharmacokinetic Effects of Humeral Intraosseous Vasopressin in a Swine Model of Ventricular Fibrillation
Authors: Burgert James M. , Johnson Arthur D. , Garcia-Blanco Jose , Fulton Lawrence V. , Loughren Michael J.
Published: March 2017

Introduction

The American Heart Association (AHA; Dallas, Texas USA) and European Resuscitation Council (Niel, Belgium) cardiac arrest (CA) guidelines recommend the intraosseous (IO) route when intravenous (IV) access cannot be obtained. Vasopressin has been used as an alternative to epinephrine to treat ventricular fibrillation (VF).

Hypothesis/Problem

Limited data exist on the pharmacokinetics and resuscitative effects of vasopressin administered by the humeral IO (HIO) route for treatment of VF. The purpose of this study was to evaluate the effects of HIO and IV vasopressin, on the occurrence, odds, and time of return of spontaneous circulation (ROSC) and pharmacokinetic measures in a swine model of VF.

Methods

Twenty-seven Yorkshire-cross swine (60 to 80 kg) were assigned randomly to three groups: HIO (n=9), IV (n=9), and a control group (n=9). Ventricular fibrillation was induced and untreated for two minutes. Chest compressions began at two minutes post-arrest and vasopressin (40 U) administered at four minutes post-arrest. Serial blood specimens were collected for four minutes, then the swine were resuscitated until ROSC or 29 post-arrest minutes elapsed.

Results

Fisher’s Exact test determined ROSC was significantly higher in the HIO 5/7 (71.5%) and IV 8/11 (72.7%) groups compared to the control 0/9 (0.0%; P=.001). Odds ratios of ROSC indicated no significant difference between the treatment groups (P=.68) but significant differences between the HIO and control, and the IV and control groups (P=.03 and .01, respectively). Analysis of Variance (ANOVA) indicated the mean time to ROSC for HIO and IV was 621.20 seconds (SD=204.21 seconds) and 554.50 seconds (SD=213.96 seconds), respectively, with no significant difference between the groups (U=11; P=.22). Multivariate Analysis of Variance (MANOVA) revealed the maximum plasma concentration (Cmax) and time to maximum concentration (Tmax) of vasopressin in the HIO and IV groups was 71753.9 pg/mL (SD=26744.58 pg/mL) and 61853.7 pg/mL (SD=22745.04 pg/mL); 111.42 seconds (SD=51.3 seconds) and 114.55 seconds (SD=55.02 seconds), respectively. Repeated measures ANOVA indicated no significant difference in plasma vasopressin concentrations between the treatment groups over four minutes (P=.48).

Conclusions

The HIO route delivered vasopressin effectively in a swine model of VF. Occurrence, time, and odds of ROSC, as well as pharmacokinetic measurements of HIO vasopressin, were comparable to IV.

BurgertJM, JohnsonAD, Garcia-BlancoJ, FultonLV, LoughrenMJ. The resuscitative and pharmacokinetic effects of humeral intraosseous vasopressin in a swine model of ventricular fibrillation. Prehosp Disaster Med. 2017;32(3):305–310.
A Qualitative Analysis of the Spontaneous Volunteer Response to the 2013 Sudan Floods: Changing the Paradigm
Authors: Albahari Amin , Schultz Carl H.
Published: March 2017

Introduction

While the concept of community resilience is gaining traction, the role of spontaneous volunteers during the initial response to disasters remains controversial. In an attempt to resolve some of the debate, investigators examined the activities of a spontaneous volunteer group called Nafeer after the Sudan floods around the city of Khartoum in August of 2013.

Hypothesis

Can spontaneous volunteers successfully initiate, coordinate, and deliver sustained assistance immediately after a disaster?

Methods

This retrospective, descriptive case study involved: (1) interviews with Nafeer members that participated in the disaster response to the Khartoum floods; (2) examination of documents generated during the event; and (3) subsequent benchmarking of their efforts with the Sphere Handbook. Members who agreed to participate were requested to provide all documents in their possession relating to Nafeer. The response by Nafeer was then benchmarked to the Sphere Handbook’s six core standards, as well as the 11 minimum standards in essential health services.

Results

A total of 11 individuals were interviewed (six from leadership and five from active members). Nafeer’s activities included: food provision; delivery of basic health care; environmental sanitation campaigns; efforts to raise awareness; and construction and strengthening of flood barricades. Its use of electronic platforms and social media to collect data and coordinate the organization’s response was effective. Nafeer adopted a flat-management structure, dividing itself into 14 committees. A Coordination Committee was in charge of liaising between all committees. The Health and Sanitation Committee supervised two health days which included mobile medical and dentistry clinics supported by a mobile laboratory and pharmacy. The Engineering Committee managed to construct and maintain flood barricades. Nafeer used crowd-sourcing to fund its activities, receiving donations locally and internationally using supporters outside Sudan. Nafeer completely fulfilled three of Sphere’s core standards and partially fulfilled the other three, but none of the essential health services standards were fulfilled. Even though the Sphere Handbook was chosen as the best available “gold standard” to benchmark Nafeer’s efforts, it showed significant limitations in effectively measuring this group.

Conclusion

It appears that independent spontaneous volunteer initiatives, like Nafeer, potentially can improve community resilience and play a significant role in the humanitarian response. Such organizations should be the subject of increased research activity. Relevant bodies should consider issuing separate guidelines supporting spontaneous volunteer organizations.

AlbahariA, SchultzCH. A qualitative analysis of the spontaneous volunteer response to the 2013 Sudan floods: changing the paradigm. Prehosp Disaster Med. 2017;32(3):240–248.
Passive intermodulation model and experimental verification of cascaded microwave devices
Authors: Li Tuanjie , Zhang Kai , Jiang Jie
Published: March 2017

Passive intermodulation (PIM) is a complex problem in high-power microwave devices and satellite communications. In this paper, an effective calculation method is proposed for predicting PIM power levels of the cascaded microwave devices. First of all, the analytical formula of intermodulation voltage is derived based on the nonlinear I–V characteristics of microwave devices. Then, the mathematical model of point sources is constructed by the transmission line theory and extended to the cascaded microwave devices. The passive intermodulation products (PIMP) of the cascaded microwave devices are evaluated based on the point-source model. The relationship of PIM between a single microwave device and the cascaded system is revealed. Eventually, the corresponding experiments are designed to verify the accuracy of point-source model and the cascaded model to predict the third-order PIM power level, which address the problem of PIM prediction of the cascaded microwave devices.
Alteration Along the Alpine Fault Helps Build Seismic Strain
Authors: Cook Terri
Published: March 2017

Detailed analysis of cores drilled through New Zealand's most dangerous on-land fault indicates that its permeability and strength are altered by mineral precipitation between seismic events.
Structural basis of a novel PD-L1 nanobody for immune checkpoint blockade
Authors: Zhang Fei , Wei Hudie , Wang Xiaoxiao , Bai Yu , Wang Pilin , Wu Jiawei , Jiang Xiaoyong , Wang Yugang , Cai Haiyan , Xu Ting , Zhou Aiwu
Published: March 2017

The use of antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in the field of cancer immunotherapy. Here, we identified KN035, an anti-PD-L1 nanobody that can strongly induce T-cell responses and inhibit tumor growth. The crystal structures of KN035 complexed with PD-L1 and free PD-L1, solved here at 1.7 and 2.7 Å resolution, respectively, show that KN035 competes with PD-1 (programmed death protein 1) for the same flat surface on PD-L1, mainly through a single surface loop of 21 amino acids. This loop forms two short helices and develops key hydrophobic and ionic interactions with PD-L1 residues, such as Ile54, Tyr56 and Arg113, which are also involved in PD-1 binding. The detailed mutagenesis study identified the hotspot residues of the PD-L1 surface and provides an explanation for the stronger (~1 000-fold) binding of KN035 to PD-L1 than PD-1 and its lack of binding to PD-L2. Overall, this study reveals how a single immunoglobulin-variable scaffold of KN035 or PD-1 can bind to a flat protein surface through either a single surface loop or beta-sheet strands; and provides a basis for designing new immune checkpoint blockers and generating bi-specific antibodies for combination therapy.
ATF3 acts as a rheostat to control JNK signalling during intestinal regeneration
Authors: Zhou Jun , Edgar Bruce A. , Boutros Michael
Published: March 2017

Epithelial barrier function is maintained by coordination of cell proliferation and cell loss, whereas barrier dysfunction can lead to disease and organismal death. JNK signalling is a conserved stress signalling pathway activated by bacterial infection and tissue damage, often leading to apoptotic cell death and compensatory cell proliferation. Here we show that the stress inducible transcription factor ATF3 restricts JNK activity in the Drosophila midgut. ATF3 regulates JNK-dependent apoptosis and regeneration through the transcriptional regulation of the JNK antagonist, Raw. Enterocyte-specific ATF3 inactivation increases JNK activity and sensitivity to infection, a phenotype that can be rescued by Raw overexpression or JNK suppression. ATF3 depletion enhances intestinal regeneration triggered by infection, but does not compensate for the loss of enterocytes and ATF3-depleted flies succumb to infection due to intestinal barrier dysfunction. In sum, we provide a mechanism to explain how an ATF3-Raw module controls JNK signalling to maintain normal intestinal barrier function during acute infection.
Stabilizing short-lived Schiff base derivatives of 5-aminouracils that activate mucosal-associated invariant T cells
Authors: Mak Jeffrey Y. W. , Xu Weijun , Reid Robert C. , Corbett Alexandra J. , Meehan Bronwyn S. , Wang Huimeng , Chen Zhenjun , Rossjohn Jamie , McCluskey James , Liu Ligong , Fairlie David P.
Published: March 2017

Mucosal-associated invariant T (MAIT) cells are activated by unstable antigens formed by reactions of 5-amino-6-D-ribitylaminouracil (a vitamin B2 biosynthetic intermediate) with glycolysis metabolites such as methylglyoxal. Here we show superior preparations of antigens in dimethylsulfoxide, avoiding their rapid decomposition in water (t1/2 1.5 h, 37 °C). Antigen solution structures, MAIT cell activation potencies (EC50 3–500 pM), and chemical stabilities are described. Computer analyses of antigen structures reveal stereochemical and energetic influences on MAIT cell activation, enabling design of a water stable synthetic antigen (EC50 2 nM). Like native antigens, this antigen preparation induces MR1 refolding and upregulates surface expression of human MR1, forms MR1 tetramers that detect MAIT cells in human PBMCs, and stimulates cytokine expression (IFNγ, TNF) by human MAIT cells. These antigens also induce MAIT cell accumulation in mouse lungs after administration with a co-stimulant. These chemical and immunological findings provide new insights into antigen properties and MAIT cell activation.
PARP1 promotes gene expression at the post-transcriptional level by modulating the RNA-binding protein HuR
Authors: Ke Yueshuang , Han Yanlong , Guo Xiaolan , Wen Jitao , Wang Ke , Jiang Xue , Tian Xue , Ba Xueqing , Boldogh Istvan , Zeng Xianlu
Published: March 2017

Poly(ADP-ribosyl)ation (PARylation) is mainly catalysed by poly-ADP-ribose polymerase 1 (PARP1), whose role in gene transcription modulation has been well established. Here we show that, in response to LPS exposure, PARP1 interacts with the adenylateuridylate-rich element-binding protein embryonic lethal abnormal vision-like 1 (Elavl1)/human antigen R (HuR), resulting in its PARylation, primarily at site D226. PARP inhibition and the D226 mutation impair HuR’s PARylation, nucleocytoplasmic shuttling and mRNA binding. Increases in mRNA level or stability of pro-inflammatory cytokines/chemokines are abolished by PARP1 ablation or inhibition, or blocked in D226A HuR-expressing cells. The present study demonstrates a mechanism to regulate gene expression at the post-transcriptional level, and suggests that blocking the interaction of PARP1 with HuR could be a strategy to treat inflammation-related diseases that involve increased mRNA stability.
Ultrafast fluxional exchange dynamics in electrolyte solvation sheath of lithium ion battery
Authors: Lee Kyung-Koo , Park Kwanghee , Lee Hochan , Noh Yohan , Kossowska Dorota , Kwak Kyungwon , Cho Minhaeng
Published: March 2017

Lithium cation is the charge carrier in lithium-ion battery. Electrolyte solution in lithium-ion battery is usually based on mixed solvents consisting of polar carbonates with different aliphatic chains. Despite various experimental evidences indicating that lithium ion forms a rigid and stable solvation sheath through electrostatic interactions with polar carbonates, both the lithium solvation structure and more importantly fluctuation dynamics and functional role of carbonate solvent molecules have not been fully elucidated yet with femtosecond vibrational spectroscopic methods. Here we investigate the ultrafast carbonate solvent exchange dynamics around lithium ions in electrolyte solutions with coherent two-dimensional infrared spectroscopy and find that the time constants of the formation and dissociation of lithium-ion···carbonate complex in solvation sheaths are on a picosecond timescale. We anticipate that such ultrafast microscopic fluxional processes in lithium-solvent complexes could provide an important clue to understanding macroscopic mobility of lithium cation in lithium-ion battery on a molecular level.
Highly selective and active CO2 reduction electrocatalysts based on cobalt phthalocyanine/carbon nanotube hybrid structures
Authors: Zhang Xing , Wu Zishan , Zhang Xiao , Li Liewu , Li Yanyan , Xu Haomin , Li Xiaoxiao , Yu Xiaolu , Zhang Zisheng , Liang Yongye , Wang Hailiang
Published: March 2017

Electrochemical reduction of carbon dioxide with renewable energy is a sustainable way of producing carbon-neutral fuels. However, developing active, selective and stable electrocatalysts is challenging and entails material structure design and tailoring across a range of length scales. Here we report a cobalt-phthalocyanine-based high-performance carbon dioxide reduction electrocatalyst material developed with a combined nanoscale and molecular approach. On the nanoscale, cobalt phthalocyanine (CoPc) molecules are uniformly anchored on carbon nanotubes to afford substantially increased current density, improved selectivity for carbon monoxide, and enhanced durability. On the molecular level, the catalytic performance is further enhanced by introducing cyano groups to the CoPc molecule. The resulting hybrid catalyst exhibits >95% Faradaic efficiency for carbon monoxide production in a wide potential range and extraordinary catalytic activity with a current density of 15.0 mA cm−2 and a turnover frequency of 4.1 s−1 at the overpotential of 0.52 V in a near-neutral aqueous solution.
Designing exotic many-body states of atomic spin and motion in photonic crystals
Authors: Manzoni Marco T. , Mathey Ludwig , Chang Darrick E.
Published: March 2017

Cold atoms coupled to photonic crystals constitute an exciting platform for exploring quantum many-body physics. For example, such systems offer the potential to realize strong photon-mediated forces between atoms, which depend on the atomic internal (spin) states, and where both the motional and spin degrees of freedom can exhibit long coherence times. An intriguing question then is whether exotic phases could arise, wherein crystalline or other spatial patterns and spin correlations are fundamentally tied together, an effect that is atypical in condensed matter systems. Here, we analyse one realistic model Hamiltonian in detail. We show that this previously unexplored system exhibits a rich phase diagram of emergent orders, including spatially dimerized spin-entangled pairs, a fluid of composite particles comprised of joint spin-phonon excitations, phonon-induced Néel ordering, and a fractional magnetization plateau associated with trimer formation.
Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression
Authors: van der Wijst Monique G. P. , van Tilburg Amanda Y. , Ruiters Marcel H. J. , Rots Marianne G.
Published: March 2017

Like the nucleus, mitochondria contain their own DNA and recent reports provide accumulating evidence that also the mitochondrial DNA (mtDNA) is subjective to DNA methylation. This evidence includes the demonstration of mitochondria-localised DNA methyltransferases and demethylases, and the detection of mtDNA methylation as well as hydroxymethylation. Importantly, differential mtDNA methylation has been linked to aging and diseases, including cancer and diabetes. However, functionality of mtDNA methylation has not been demonstrated. Therefore, we targeted DNA methylating enzymes (modifying cytosine in the CpG or GpC context) to the mtDNA. Unexpectedly, mtDNA gene expression remained unchanged upon induction of CpG mtDNA methylation, whereas induction of C-methylation in the GpC context decreased mtDNA gene expression. Intriguingly, in the latter case, the three mtDNA promoters were differentially affected in each cell line, while cellular function seemed undisturbed. In conclusion, this is the first study which directly addresses the potential functionality of mtDNA methylation. Giving the important role of mitochondria in health and disease, unravelling the impact of mtDNA methylation adds to our understanding of the role of mitochondria in physiological and pathophysiological processes.
First record of gregarines (Apicomplexa) in seminal vesicle of insect
Authors: Dias Glenda , Dallai Romano , Carapelli Antonio , Almeida João P. P. , Campos Lucio A. O. , Faroni Leda R. A. , Lino-Neto José
Published: March 2017

Gregarines (Apicomplexa) are a diverse group of protozoan parasites, which infects gut and other body cavities of invertebrate hosts. In reproductive system of insects, gregarine has been reported only in the accessory glands and spermathecae of females; therefore, this is the first report of a gregarine species in seminal vesicles of insects. Different developmental stages, including sporozoytes, oocysts and trophozoites were described from morphological descriptions using light and electron transmission microscopy. The parasites were described in seminal vesicles of the beetle Tribolium castaneum a model organism and an important insect pest. DNA sequence analysis suggests that the protozoan parasite was an Ascogregarina sp.
Multimodal brain imaging with magnetoencephalography: A method for measuring blood pressure and cardiorespiratory oscillations
Authors: Myllylä Teemu , Zacharias Norman , Korhonen Vesa , Zienkiewicz Aleksandra , Hinrichs Hermann , Kiviniemi Vesa , Walter Martin
Published: March 2017

Studies with magnetoencephalography (MEG) are still quite rarely combined simultaneously with methods that can provide a metabolic dimension to MEG investigations. In addition, continuous blood pressure measurements which comply with MEG compatibility requirements are lacking. For instance, by combining methods reflecting neurovascular status one could obtain more information on low frequency fluctuations that have recently gained increasing interest as a mediator of functional connectivity within brain networks. This paper presents a multimodal brain imaging setup, capable to non-invasively and continuously measure cerebral hemodynamic, cardiorespiratory and blood pressure oscillations simultaneously with MEG. In the setup, all methods apart from MEG rely on the use of fibre optics. In particular, we present a method for measuring of blood pressure and cardiorespiratory oscillations continuously with MEG. The potential of this type of multimodal setup for brain research is demonstrated by our preliminary studies on human, showing effects of mild hypercapnia, gathered simultaneously with the presented modalities.
Multifunctional Nanographene Oxide for Targeted Gene-Mediated Thermochemotherapy of Drug-resistant Tumour
Authors: Zeng Yiping , Yang Zhangyou , Li Hong , Hao Yuhui , Liu Cong , Zhu Lin , Liu Jing , Lu Binghui , Li Rong
Published: March 2017

Drug resistance remains a major challenge for anticancer treatment, and one of the major mechanisms of drug resistance is the overexpression of drug efflux transporters in cancer. A new approach for defeating drug resistance is the use of a co-delivery strategy that utilizes small interfering RNA (siRNA) to silence the expression of efflux transporters together with a suitable anticancer drug for drug-resistant cells. In this work, multifunctional graphene capable of integrating multiple functions in one system was employed as a novel co-delivery system for siRNA and doxorubicin (Dox), as well as for the controlled release of intracellular pH-triggered and heat-triggered Dox. Additionally, it was used as a synergistic therapy based on the photothermal effect of graphene oxide (GO) under near-infrared (NIR) irradiation and the chemotherapeutic effect of Dox. The nanocomplex exhibited high drug and siRNA loading. Furthermore, the dual delivery of siRNA and Dox by folic acid (FA)-conjugated polyethylenimine-modified PEGylated nanographene (PPG-FA/siRNA/Dox) exhibited a satisfactory gene silencing effect as well as efficient intracellular delivery of Dox. Thus, Dox could access the nucleus and induce greater cytotoxicity compared with siRNA-absent delivery systems. Significantly, under irradiation, the combined treatment showed more synergistic effect for overcoming drug resistance compared with chemotherapy effect alone.
Structure Evolution and Multiferroic Properties in Cobalt Doped Bi4NdTi3Fe1-xCoxO15-Bi3NdTi2Fe1-xCoxO12-δ Intergrowth Aurivillius Compounds
Authors: Zhang D. L. , Huang W. C. , Chen Z. W. , Zhao W. B. , Feng L. , Li M. , Yin Y. W. , Dong S. N. , Li X. G.
Published: March 2017

Here, we report the structure evolution, magnetic and ferroelectric properties in Co-doped 4- and 3-layered intergrowth Aurivillius compounds Bi4NdTi3Fe1-xCoxO15-Bi3NdTi2Fe1-xCoxO12-δ. The compounds suffer a structure evolution from the parent 4-layered phase (Bi4NdTi3FeO15) to 3-layered phase (Bi3NdTi2CoO12-δ) with increasing cobalt doping level from 0 to 1. Meanwhile the remanent magnetization and polarization show opposite variation tendencies against the doping level, and the sample with x = 0.3 has the largest remanent magnetization and the smallest polarization. It is believed that the Co concentration dependent magnetic properties are related to the population of the Fe3+ -O-Co3+ bonds, while the suppressed ferroelectric polarization is due to the enhanced leakage current caused by the increasing Co concentration. Furthermore, the samples (x = 0.1–0.7) with ferromagnetism show magnetoelectric coupling effects at room temperature. The results indicate that it is an effective method to create new multiferroic materials through modifying natural superlattices.
Vesicle miR-195 derived from Endothelial Cells Inhibits Expression of Serotonin Transporter in Vessel Smooth Muscle Cells
Authors: Gu Junzhong , Zhang Huiyuan , Ji Bingyang , Jiang Hui , Zhao Tao , Jiang Rongcai , Zhang Zhiren , Tan Shengjiang , Ahmed Asif , Gu Yuchun
Published: March 2017

Serotonin or 5-hydroxytryptamine (5-HT) has been shown to be essential in lots of physiological and pathological processes. It is well known that 5-HT and 5-HT transporter (5-HTT) play important roles in the pulmonary artery in pulmonary hypertension. However, little is known about the function of 5-HTT in other arteries. In this study we found that the expression of 5-HTT was elevated in injured carotid arteries and over-expression of 5-HTT induced proliferation of smooth muscle cells (SMCs); however, this phenotype could be reversed by knocking-down of 5-HTT or endothelial cells conditional medium (EC-CM). A 5-HTT inhibitor, fluoxetine, treated animals also exhibited reduced restenosis after injury. We identified that miR-195 was packaged in the extracellular vesicles from EC-CM. We further confirmed that extracellular vesicles could transfer miR-195 from ECs to SMCs to inhibit the expression of 5-HTT in SMCs and the proliferation of SMCs. These results provide the first evidence that ECs communicate with SMCs via micro-RNA195 in the regulation of the proliferation of SMCs through 5-HTT, which will contribute to a better understanding of communications between ECs and SMCs via micro-RNA. Our findings suggest a potential target for the control of vessel restenosis.
Waist-hip Ratio (WHR), a Better Predictor for Prostate Cancer than Body Mass Index (BMI): Results from a Chinese Hospital-based Biopsy Cohort
Authors: Tang Bo , Han Cheng-Tao , Zhang Gui-Ming , Zhang Cui-Zhu , Yang Wei-Yi , Shen Ying , Vidal Adriana C. , Freedland Stephen J. , Zhu Yao , Ye Ding-Wei
Published: March 2017

To investigate whether waist-hip ratio (WHR) is a better predictor of prostate cancer (PCa) incidence than body mass index (BMI) in Chinese men. Of consecutive patients who underwent prostate biopsies in one tertiary center between 2013 and 2015, we examined data on 1018 with PSA ≤20 ng/ml. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the associations between BMI, WHR and PCa incidence. Area under the ROC (AUC) was used to evaluate the accuracy of different prognostic models. A total of 255 men and 103 men were diagnosed with PCa and high grade PCa (HGPCa, Gleason score ≥8). WHR was an independent risk factor for both PCa (OR = 1.07 95%Cl 1.03–1.11) and HGPCa (OR = 1.14 95%Cl 1.09–1.19) detection, while BMI had no relationship with either PCa or HGPCa detection. Adding WHR to a multivariable model increased the AUC for detecting HGPCa from 0.66 (95%Cl 0.60–0.72) to 0.71 (95%Cl 0.65–0.76). In this Chinese cohort, WHR was significantly predictive of PCa and HGPCa. Adding WHR to a multivariable model increased the diagnostic accuracy for detecting HGPCa. If confirmed, including WHR measurement may improve PCa and HGPCa detection.
Protein expression guided chemical profiling of living cells by the simultaneous observation of Raman scattering and anti-Stokes fluorescence emission
Authors: Chiu Liang-da , Ichimura Taro , Sekiya Takumasa , Machiyama Hiroaki , Watanabe Tomonobu , Fujita Hideaki , Ozawa Takeaki , Fujita Katsumasa
Published: March 2017

Our current understanding of molecular biology provides a clear picture of how the genome, transcriptome and proteome regulate each other, but how the chemical environment of the cell plays a role in cellular regulation remains much to be studied. Here we show an imaging method using hybrid fluorescence-Raman microscopy that measures the chemical micro-environment associated with protein expression patterns in a living cell. Simultaneous detection of fluorescence and Raman signals, realised by spectrally separating the two modes through the single photon anti-Stokes fluorescence emission of fluorescent proteins, enables the accurate correlation of the chemical fingerprint of a specimen to its physiological state. Subsequent experiments revealed the slight chemical differences that enabled the chemical profiling of mouse embryonic stem cells with and without Oct4 expression. Furthermore, using the fluorescent probe as localisation guide, we successfully analysed the detailed chemical content of cell nucleus and Golgi body. The technique can be further applied to a wide range of biomedical studies for the better understanding of chemical events during biological processes.
Superior Adsorption and Regenerable Dye Adsorbent Based on Flower-Like Molybdenum Disulfide Nanostructure
Authors: Han Sancan , Liu Kerui , Hu Linfeng , Teng Feng , Yu Pingping , Zhu Yufang
Published: March 2017

Herein we report superior dye-adsorption performance for flower-like nanostructure composed of two dimensional (2D) MoS2 nanosheets by a facile hydrothermal method, more prominent adsorption of cationic dye compared with anodic dye indicates the dye adsorption performance strongly depends on surface charge of MoS2 nanosheets. The adsorption mechanism of dye is analyzed, the kinetic data of dye adsorption fit well with the pseudo-second-order model, meanwhile adsorption capability at different equilibrium concentrations follows Langmuir model, indicating the favorability and feasibility of dye adsorption. The regenerable property for MoS2 with full adsorption of dye molecules by using alkaline solution were demonstrated, showing the feasibility of reuse for the MoS2, which is promising in its practical water treatment application.
Excessive fruit consumption during the second trimester is associated with increased likelihood of gestational diabetes mellitus: a prospective study
Authors: Huang Wu-Qing , Lu Ying , Xu Ming , Huang Jing , Su Yi-Xiang , Zhang Cai-Xia
Published: March 2017

This study aimed to investigate the association between fruit consumption during the second trimester and the occurrence of gestational diabetes mellitus (GDM). A prospective study with 772 female participants was conducted in China from April 2013 to August 2014. Dietary intake was assessed in face-to-face and telephone interviews using a 3-day food record. GDM was ascertained using a standard 75 g 2 hour oral glucose tolerance test. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for various confounders. Of the 772 participants, 169 were diagnosed with GDM during the period under study. Greater total fruit consumption during the second trimester was associated with a higher likelihood of GDM (highest vs. lowest quartile: adjusted OR4.82, 95% CI 2.38 to 9.76). Fruits with a moderate or high glycaemic index (GI) were positively associated with the occurrence of GDM. Fruit subgroups were also categorised by polyphenol content, and tropical-fruit and citrus-fruit consumption was found to be positively related to the occurrence of GDM. These findings suggest that the excessive consumption of fruit, especially fruit with moderate or high GI values, tropical-fruit and citrus-fruit, increases the likelihood of GDM.
Co3O4 nanoparticles anchored on nitrogen-doped reduced graphene oxide as a multifunctional catalyst for H2O2 reduction, oxygen reduction and evolution reaction
Authors: Zhang Tingting , He Chuansheng , Sun Fengzhan , Ding Yongqi , Wang Manchao , Peng Lin , Wang Jiahui , Lin Yuqing
Published: March 2017

This study describes a facile and effective route to synthesize hybrid material consisting of Co3O4 nanoparticles anchored on nitrogen-doped reduced graphene oxide (Co3O4/N-rGO) as a high-performance tri-functional catalyst for oxygen reduction reaction (ORR), oxygen evolution reaction (OER) and H2O2 sensing. Electrocatalytic activity of Co3O4/N-rGO to hydrogen peroxide reduction was tested by cyclic voltammetry (CV), linear sweep voltammetry (LSV) and chronoamperometry. Under a reduction potential at −0.6 V to H2O2, this constructing H2O2 sensor exhibits a linear response ranging from 0.2 to 17.5 mM with a detection limit to be 0.1 mM. Although Co3O4/rGO or nitrogen-doped reduced graphene oxide (N-rGO) alone has little catalytic activity, the Co3O4/N-rGO exhibits high ORR activity. The Co3O4/N-rGO hybrid demonstrates satisfied catalytic activity with ORR peak potential to be −0.26 V (vs. Ag/AgCl) and the number of electron transfer number is 3.4, but superior stability to Pt/C in alkaline solutions. The same hybrid is also highly active for OER with the onset potential, current density and Tafel slope to be better than Pt/C. The unusual catalytic activity of Co3O4/N-rGO for hydrogen peroxide reduction, ORR and OER may be ascribed to synergetic chemical coupling effects between Co3O4, nitrogen and graphene.
A Murine Model to Study Epilepsy and SUDEP Induced by Malaria Infection
Authors: Ssentongo Paddy , Robuccio Anna E. , Thuku Godfrey , Sim Derek G. , Nabi Ali , Bahari Fatemeh , Shanmugasundaram Balaji , Billard Myles W. , Geronimo Andrew , Short Kurt W. , Drew Patrick J. , Baccon Jennifer , Weinstein Steven L. , Gilliam Frank G. , Stoute José A. , Chinchilli Vernon M. , Read Andrew F. , Gluckman Bruce J. , Schiff Steven J.
Published: March 2017

One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background. We also discovered spontaneous sudden unexpected death in epilepsy (SUDEP) in two of our strain combinations. These models offer a platform to enable new preclinical research into mechanisms and prevention of epilepsy and SUDEP.
Zinc oxide nanorod field effect transistor for long-time cellular force measurement
Authors: Zong Xianli , Zhu Rong
Published: March 2017

Mechanical forces generated by cells are known to influence a vast range of cellular functions ranging from receptor signaling and transcription to differentiation and proliferation. We report a novel measurement approach using zinc oxide nanorods as a peeping transducer to monitor dynamic mechanical behavior of cellular traction on surrounding substrate. We develop a ZnO nanorod field effect transistor (FET) as an ultrasensitive force sensor to realize long-time, unstained, and in-situ detection of cell cycle phases, including attachment, spread, and mitosis. Excellent biocompatibility and ultra-sensitivity of the biomechanical measurement is ensured by coating a parylene film on the FET sensor as a concealment, which provides complete electronic isolation between the sensor and cell. With unique features of ultra-sensitivity, label-free, easy handling, and good biocompatibility, the force sensor allows feasible for tracking cellular dynamics in physiological contexts and understanding their contribution to biological processes.
Off-axis points encoding/decoding with orbital angular momentum spectrum
Authors: Chu Jiaqi , Chu Daping , Smithwitck Quinn
Published: March 2017

Encoding/decoding off-axis points with discrete orbital angular momentum (OAM) modes is investigated. On-axis Laguerre-Gaussian (LG) beams are expanded into off-axis OAM spectra, with which off-axis points are encoded. The influence of the mode and the displacement of the LG beam on the spread of the OAM spectrum is analysed. The results show that not only the conventional on-axis point, but also off-axis points, can be encoded and decoded with OAM of light. This is confirmed experimentally. The analytical result here provides a solid foundation to use OAM modes to encode two-dimensional high density information for multiplexing and to analyse the effect of mis-alignment in practical OAM applications.
Optogenetic control of the Dab1 signaling pathway
Authors: Wang Liang , Cooper Jonathan A.
Published: March 2017

The Reelin-Dab1 signaling pathway regulates development of the mammalian brain, including neuron migrations in various brain regions, as well as learning and memory in adults. Extracellular Reelin binds to cell surface receptors and activates phosphorylation of the intracellular Dab1 protein. Dab1 is required for most effects of Reelin, but Dab1-independent pathways may contribute. Here we developed a single-component, photoactivatable Dab1 (opto-Dab1) by using the blue light-sensitive dimerization/oligomerization property of A. thaliana Cryptochrome 2 (Cry2). Opto-Dab1 can activate downstream signals rapidly, locally, and reversibly upon blue light illumination. The high spatiotemporal resolution of the opto-Dab1 probe also allows us to control membrane protrusion, retraction and ruffling by local illumination in both COS7 cells and in primary neurons. This shows that Dab1 activation is sufficient to orient cell movement in the absence of other signals. Opto-Dab1 may be useful to study the biological functions of the Reelin-Dab1 signaling pathway both in vitro and in vivo.
Three-dimensional Organization of Layered Apical Cytoskeletal Networks Associated with Mouse Airway Tissue Development
Authors: Tateishi Kazuhiro , Nishida Tomoki , Inoue Kanako , Tsukita Sachiko
Published: March 2017

The cytoskeleton is an essential cellular component that enables various sophisticated functions of epithelial cells by forming specialized subcellular compartments. However, the functional and structural roles of cytoskeletons in subcellular compartmentalization are still not fully understood. Here we identified a novel network structure consisting of actin filaments, intermediate filaments, and microtubules directly beneath the apical membrane in mouse airway multiciliated cells and in cultured epithelial cells. Three-dimensional imaging by ultra-high voltage electron microscopy and immunofluorescence revealed that the morphological features of each network depended on the cell type and were spatiotemporally integrated in association with tissue development. Detailed analyses using Odf2 mutant mice, which lack ciliary basal feet and apical microtubules, suggested a novel contribution of the intermediate filaments to coordinated ciliary beating. These findings provide a new perspective for viewing epithelial cell differentiation and tissue morphogenesis through the structure and function of apical cytoskeletal networks.
Long-term Effect of Radiotherapy in Rectal Cancer Patients with Mucinous Tumor: A Large Population Based Study
Authors: Guan Xu , Jia Senhao , Chen Wei , Jiang Zheng , Liu Zheng , Chen Yinggang , Wang Guiyu , Wang Xishan
Published: March 2017

Due to distinct biological behavior of mucinous adenocarcinoma (MAC) and signet ring cell cancer (SRC), the efficacy of radiotherapy on long-term outcome for rectal cancer (RC) patients with mucinous tumors is still unclear. Here, we identified 1808 RC patients with MAC/SRC from Surveillance, Epidemiology, and End-Results (SEER) database from 2004 to 2013. Patients were divided into two subgroups according to different therapeutic strategies, including surgery alone and surgery combined with radiotherapy. Kaplan–Meier methods and Cox regression models were used to access the influence of therapeutic strategy on long-term survival outcomes. The 5-year and 10-year cancer specific survival (CSS) were improved in stage II and III patients who underwent surgery and radiotherapy compared with patients who underwent surgery alone. These results were further confirmed following propensity score matching. In addition, radiotherapy was deemed as independent good prognostic factor in patient with MAC/SRC. In subgroup analysis, the result also demonstrated that long-term survival was improved following radiotherapy. However, there was no prognostic difference between preoperative and postoperative radiotherapy. In conclusion, radiotherapy could improve survival for RC patients with MAC and SRC, but only for patients in stage II and III. This finding supported the application of radiotherapy in clinical practice.
Computational Modeling of complete HOXB13 protein for predicting the functional effect of SNPs and the associated role in hereditary prostate cancer
Authors: Chandrasekaran Gopalakrishnan , Hwang Eu Chang , Kang Taek Won , Kwon Dong Deuk , Park Kwangsung , Lee Je-Jung , Lakshmanan Vinoth-Kumar
Published: March 2017

The human HOXB13 gene encodes a 284 amino acid transcription factor belonging to the homeobox gene family containing a homeobox and a HoxA13 N-terminal domain. It is highly linked to hereditary prostate cancer, the majority of which is manifested as a result of a Single Nucleotide Polymorphism (SNP). In silico analysis of 95 missense SNP’s corresponding to the non-homeobox region of HOXB13 predicted 21 nsSNP’s to be potentially deleterious. Among 123 UTR SNPs analysed by UTRScan, rs543028086, rs550968159, rs563065128 were found to affect the UNR_BS, GY-BOX and MBE UTR signals, respectively. Subsequent analysis by PolymiRTS revealed 23 UTR SNPs altering the miRNA binding site. The complete HOXB13_M26 protein structure was modelled using MODELLER v9.17. Computational analysis of the 21 nsSNP’s mapped into the HOXB13_M26 protein revealed seven nsSNP’s (rs761914407, rs8556, rs138213197, rs772962401, rs778843798, rs770620686 and rs587780165) seriously resulting in a damaging and deleterious effect on the protein. G84E, G135E, and A128V resulted in increased, while, R215C, C66R, Y80C and S122R resulted in decreased protein stability, ultimately predicted to result in the altered binding patterns of HOXB13. While the genotype-phenotype based effects of nsSNP’s were assessed, the exact biological and biochemical mechanism driven by the above predicted SNPs still needs to be extensively evaluated by in vivo and GWAS studies.
Identification of Topological Network Modules in Perturbed Protein Interaction Networks
Authors: Sardiu Mihaela E. , Gilmore Joshua M. , Groppe Brad , Florens Laurence , Washburn Michael P.
Published: March 2017

Biological networks consist of functional modules, however detecting and characterizing such modules in networks remains challenging. Perturbing networks is one strategy for identifying modules. Here we used an advanced mathematical approach named topological data analysis (TDA) to interrogate two perturbed networks. In one, we disrupted the S. cerevisiae INO80 protein interaction network by isolating complexes after protein complex components were deleted from the genome. In the second, we reanalyzed previously published data demonstrating the disruption of the human Sin3 network with a histone deacetylase inhibitor. Here we show that disrupted networks contained topological network modules (TNMs) with shared properties that mapped onto distinct locations in networks. We define TMNs as proteins that occupy close network positions depending on their coordinates in a topological space. TNMs provide new insight into networks by capturing proteins from different categories including proteins within a complex, proteins with shared biological functions, and proteins disrupted across networks.
Standoff Detection of Uranium and its Isotopes by Femtosecond Filament Laser Ablation Molecular Isotopic Spectrometry
Authors: Hartig Kyle C. , Ghebregziabher Isaac , Jovanovic Igor
Published: March 2017

The ability to perform not only elementally but also isotopically sensitive detection and analysis at standoff distances is impor-tant for remote sensing applications in diverse ares, such as nuclear nonproliferation, environmental monitoring, geophysics, and planetary science. We demonstrate isotopically sensitive real-time standoff detection of uranium by the use of femtosecond filament-induced laser ablation molecular isotopic spectrometry. A uranium oxide molecular emission isotope shift of 0.05 ± 0.007 nm is reported at 593.6 nm. We implement both spectroscopic and acoustic diagnostics to characterize the properties of uranium plasma generated at different filament-uranium interaction points. The resulting uranium oxide emis-sion exhibits a nearly constant signal-to-background ratio over the length of the filament, unlike the uranium atomic and ionic emission, for which the signal-to-background ratio varies significantly along the filament propagation. This is explained by the different rates of increase of plasma density and uranium oxide density along the filament length resulting from spectral and temporal evolution of the filament along its propagation. The results provide a basis for the optimal use of filaments for standoff detection and analysis of uranium isotopes and indicate the potential of the technique for a wider range of remote sensing applications that require isotopic sensitivity.
Assembling Ordered Nanorod Superstructures and Their Application as Microcavity Lasers
Authors: Liu Pai , Singh Shalini , Guo Yina , Wang Jian-Jun , Xu Hongxing , Silien Christophe , Liu Ning , Ryan Kevin M.
Published: March 2017

Herein we report the formation of multi-layered arrays of vertically aligned and close packed semiconductor nanorods in perfect registry at a substrate using electric field assisted assembly. The collective properties of these CdSexS1-x nanorod emitters are harnessed by demonstrating a relatively low amplified spontaneous emission (ASE) threshold and a high net optical gain at medium pump intensity. The importance of order in the system is highlighted where a lower ASE threshold is observed compared to disordered samples.
SNP-SNP interactions between WNT4 and WNT5A were associated with obesity related traits in Han Chinese Population
Authors: Dong Shan-Shan , Hu Wei-Xin , Yang Tie-Lin , Chen Xiao-Feng , Yan Han , Chen Xiang-Ding , Tan Li-Jun , Tian Qing , Deng Hong-Wen , Guo Yan
Published: March 2017

Considering the biological roles of WNT4 and WNT5A involved in adipogenesis, we aimed to investigate whether SNPs in WNT4 and WNT5A contribute to obesity related traits in Han Chinese population. Targeted genomic sequence for WNT4 and WNT5A was determined in 100 Han Chinese subjects and tag SNPs were selected. Both single SNP and SNP × SNP interaction association analyses with body mass index (BMI) were evaluated in the 100 subjects and another independent sample of 1,627 Han Chinese subjects. Meta-analyses were performed and multiple testing corrections were carried out using the Bonferroni method. Consistent with the Genetic Investigation of ANthropometric Traits (GIANT) dataset results, we didn’t detect significant association signals in single SNP association analyses. However, the interaction between rs2072920 and rs11918967, was associated with BMI after multiple testing corrections (combined P = 2.20 × 10−4). The signal was also significant in each contributing data set. SNP rs2072920 is located in the 3′-UTR of WNT4 and SNP rs11918967 is located in the intron of WNT5A. Functional annotation results revealed that both SNPs might be involved in transcriptional regulation of gene expression. Our results suggest that a combined effect of SNPs via WNT4-WNT5A interaction may affect the variation of BMI in Han Chinese population.