bluuebunny/crossref_metadata_2025 huggingface dataset:
Subcellular western blotting of single cells
Authors: Yamauchi Kevin A. , Herr Amy E.
Published: February 2017

Although immunoassays are the de facto standard for determining subcellular protein localization in individual cells, antibody probe cross-reactivity and fixation artifacts remain confounding factors. To enhance selectivity while providing single-cell resolution, we introduce a subcellular western blotting technique capable of separately assaying proteins in the 14 pL cytoplasm and 2 pL nucleus of individual cells. To confer precision fluidic control, we describe a passive multilayer microdevice that leverages the rapid transport times afforded by miniaturization. After isolating single cells in microwells, we apply single-cell differential detergent fractionation to lyse and western blot the cytoplasmic lysate, whereas the nucleus remains intact in the microwell. Subsequently, we lyse the intact nucleus and western blot the nuclear lysate. To index each protein analysis to the originating subcellular compartment, we utilize bi-directional electrophoresis, a multidimensional separation that assays the lysate from each compartment in a distinct region of the separation axis. Single-cell bi-directional electrophoresis eliminates the need for semi-subjective image segmentation algorithms required in immunocytochemistry. The subcellular, single-cell western blot is demonstrated for six targets per cell, and successfully localizes spliceosome-associated proteins solubilized from large protein and RNA complexes, even for closely sized proteins (a 7 kDa difference). Measurement of NF-κB translocation dynamics in unfixed cells at 15-min intervals demonstrates reduced technical variance compared with immunofluorescence. This chemical cytometry assay directly measures the nucleocytoplasmic protein distribution in individual unfixed cells, thus providing insight into protein signaling in heterogeneous cell populations.
IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes
Authors: Almine Jessica F. , O’Hare Craig A. J. , Dunphy Gillian , Haga Ismar R. , Naik Rangeetha J. , Atrih Abdelmadjid , Connolly Dympna J. , Taylor Jordan , Kelsall Ian R. , Bowie Andrew G. , Beard Philippa M. , Unterholzner Leonie
Published: February 2017

Many human cells can sense the presence of exogenous DNA during infection though the cytosolic DNA receptor cyclic GMP-AMP synthase (cGAS), which produces the second messenger cyclic GMP-AMP (cGAMP). Other putative DNA receptors have been described, but whether their functions are redundant, tissue-specific or integrated in the cGAS-cGAMP pathway is unclear. Here we show that interferon-γ inducible protein 16 (IFI16) cooperates with cGAS during DNA sensing in human keratinocytes, as both cGAS and IFI16 are required for the full activation of an innate immune response to exogenous DNA and DNA viruses. IFI16 is also required for the cGAMP-induced activation of STING, and interacts with STING to promote STING phosphorylation and translocation. We propose that the two DNA sensors IFI16 and cGAS cooperate to prevent the spurious activation of the type I interferon response.
Exfoliation of natural van der Waals heterostructures to a single unit cell thickness
Authors: Velický Matěj , Toth Peter S. , Rakowski Alexander M. , Rooney Aidan P. , Kozikov Aleksey , Woods Colin R. , Mishchenko Artem , Fumagalli Laura , Yin Jun , Zólyomi Viktor , Georgiou Thanasis , Haigh Sarah J. , Novoselov Kostya S. , Dryfe Robert A. W.
Published: February 2017

Weak interlayer interactions in van der Waals crystals facilitate their mechanical exfoliation to monolayer and few-layer two-dimensional materials, which often exhibit striking physical phenomena absent in their bulk form. Here we utilize mechanical exfoliation to produce a two-dimensional form of a mineral franckeite and show that the phase segregation of chemical species into discrete layers at the sub-nanometre scale facilitates franckeite’s layered structure and basal cleavage down to a single unit cell thickness. This behaviour is likely to be common in a wider family of complex minerals and could be exploited for a single-step synthesis of van der Waals heterostructures, as an alternative to artificial stacking of individual two-dimensional crystals. We demonstrate p-type electrical conductivity and remarkable electrochemical properties of the exfoliated crystals, showing promise for a range of applications, and use the density functional theory calculations of franckeite’s electronic band structure to rationalize the experimental results.
Induced p53 loss in mouse luminal cells causes clonal expansion and development of mammary tumours
Authors: Tao Luwei , Xiang Dongxi , Xie Ying , Bronson Roderick T. , Li Zhe
Published: February 2017

Most breast cancers may have a luminal origin. TP53 is one of the most frequently mutated genes in breast cancers. However, how p53 deficiency contributes to breast tumorigenesis from luminal cells remains elusive. Here we report that induced p53 loss in Krt8+ mammary luminal cells leads to their clonal expansion without directly affecting their luminal identity. All induced mice develop mammary tumours with 9qA1 (Yap1) and/or 6qA2 (Met) amplification(s). These tumours exhibit a mammary stem cell (MaSC)-like expression signature and most closely resemble claudin-low breast cancer. Thus, although p53 does not directly control the luminal fate, its loss facilitates acquisition of MaSC-like properties by luminal cells and predisposes them to development of mammary tumours with loss of luminal identity. Our data also suggest that claudin-low breast cancer can develop from luminal cells, possibly via a basal-like intermediate state, although further study using a different luminal promoter is needed to fully support this conclusion.
Integrative analyses of transcriptome sequencing identify novel functional lncRNAs in esophageal squamous cell carcinoma
Authors: Li C-Q , Huang G-W , Wu Z-Y , Xu Y-J , Li X-C , Xue Y-J , Zhu Y , Zhao J-M , Li M , Zhang J , Wu J-Y , Lei F , Wang Q-Y , Li S , Zheng C-P , Ai B , Tang Z-D , Feng C-C , Liao L-D , Wang S-H , Shen J-H , Liu Y-J , Bai X-F , He J-Z , Cao H-H , Wu B-L , Wang M-R , Lin D-C , Koeffler H P , Wang L-D , Li X , Li E-M , Xu L-Y
Published: February 2017

Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.
Molecular dynamics simulations reveal ligand-controlled positioning of a peripheral protein complex in membranes
Authors: Ryckbosch Steven M. , Wender Paul A. , Pande Vijay S.
Published: February 2017

Bryostatin is in clinical trials for Alzheimer’s disease, cancer, and HIV/AIDS eradication. It binds to protein kinase C competitively with diacylglycerol, the endogenous protein kinase C regulator, and plant-derived phorbol esters, but each ligand induces different activities. Determination of the structural origin for these differing activities by X-ray analysis has not succeeded due to difficulties in co-crystallizing protein kinase C with relevant ligands. More importantly, static, crystal-lattice bound complexes do not address the influence of the membrane on the structure and dynamics of membrane-associated proteins. To address this general problem, we performed long-timescale (400–500 µs aggregate) all-atom molecular dynamics simulations of protein kinase C–ligand–membrane complexes and observed that different protein kinase C activators differentially position the complex in the membrane due in part to their differing interactions with waters at the membrane inner leaf. These new findings enable new strategies for the design of simpler, more effective protein kinase C analogs and could also prove relevant to other peripheral protein complexes.
Specific membrane capacitance, cytoplasm conductivity and instantaneous Young’s modulus of single tumour cells
Authors: Wang Ke , Zhao Yang , Chen Deyong , Fan Beiyuan , Lu Yulan , Chen Lianhong , Long Rong , Wang Junbo , Chen Jian
Published: February 2017

As label-free biomarkers, biophysical properties of cells are widely used for cell type classification. However, intrinsic biophysical markers, e.g., specific membrane capacitance (Cspecific membrane), cytoplasm conductivity (σconductivity) and instantaneous Young’s modulus (Einstantaneous) measured for hundreds of single cells were not yet reported. In this study, single cells in suspension (adherent cells treated with trypsin) were aspirated through a microfluidic constriction channel at 25 °C, and the entry processes and impedance profiles were recorded and translated to Cspecific membrane, σconductivity and Einstantaneous. Cspecific membrane, σconductivity and Einstantaneous of five cell types were quantified as 2.10±0.38 μF cm−2, 0.91±0.15 S m−1 and 5.52±0.95 kPa for H460 cells (ncell=437); 2.52±0.54 μF cm−2, 0.83±0.12 S m−1 and 5.54±1.04 kPa for H446 cells (ncell=410); 2.45±0.57 μF cm−2, 0.99±0.18 S m−1 and 5.16±1.68 kPa for A549 cells (ncell=442); 1.86±0.31 μF cm−2, 1.07±0.18 S m−1 and 3.86±0.81 kPa for 95D cells (ncell=415); 2.03±0.35 μF cm−2, 0.99±0.16 S m−1 and 3.49±0.70 kPa for 95C cells (ncell=290). The database of Cspecific membrane, σconductivity and Einstantaneous may serve as a reference for future studies of cellular biophysical properties.
The French Muséum national d’histoire naturelle vascular plant herbarium collection dataset
Authors: Le Bras Gwenaël , Pignal Marc , Jeanson Marc L. , Muller Serge , Aupic Cécile , Carré Benoît , Flament Grégoire , Gaudeul Myriam , Gonçalves Claudia , Invernón Vanessa R. , Jabbour Florian , Lerat Elodie , Lowry Porter P. , Offroy Bérangère , Pimparé Eva Pérez , Poncy Odile , Rouhan Germinal , Haevermans Thomas
Published: February 2017

We provide a quantitative description of the French national herbarium vascular plants collection dataset. Held at the Muséum national d’histoire naturelle, Paris, it currently comprises records for 5,400,000 specimens, representing 90% of the estimated total of specimens. Ninety nine percent of the specimen entries are linked to one or more images and 16% have field-collecting information available. This major botanical collection represents the results of over three centuries of exploration and study. The sources of the collection are global, with a strong representation for France, including overseas territories, and former French colonies. The compilation of this dataset was made possible through numerous national and international projects, the most important of which was linked to the renovation of the herbarium building. The vascular plant collection is actively expanding today, hence the continuous growth exhibited by the dataset, which can be fully accessed through the GBIF portal or the MNHN database portal (available at: https://science.mnhn.fr/institution/mnhn/collection/p/item/search/form). This dataset is a major source of data for systematics, global plants macroecological studies or conservation assessments.
The Mole Mapper Study, mobile phone skin imaging and melanoma risk data collected using ResearchKit
Authors: Webster Dan E. , Suver Christine , Doerr Megan , Mounts Erin , Domenico Lisa , Petrie Tracy , Leachman Sancy A. , Trister Andrew D. , Bot Brian M.
Published: February 2017

Sensor-embedded phones are an emerging facilitator for participant-driven research studies. Skin cancer research is particularly amenable to this approach, as phone cameras enable self-examination and documentation of mole abnormalities that may signal a progression towards melanoma. Aggregation and open sharing of this participant-collected data can be foundational for research and the development of early cancer detection tools. Here we describe data from Mole Mapper, an iPhone-based observational study built using the Apple ResearchKit framework. The Mole Mapper app was designed to collect participant-provided images and measurements of moles, together with demographic and behavioral information relating to melanoma risk. The study cohort includes 2,069 participants who contributed 1,920 demographic surveys, 3,274 mole measurements, and 2,422 curated mole images. Survey data recapitulates associations between melanoma and known demographic risks, with red hair as the most significant factor in this cohort. Participant-provided mole measurements indicate an average mole size of 3.95 mm. These data have been made available to engage researchers in a collaborative, multidisciplinary effort to better understand and prevent melanoma.
Patterned transparent electrode with a continuous distribution of silver nanowires produced by an etching-free patterning method
Authors: Shin Kwonwoo , Park Ji Sun , Han Jong Hun , Choi Yunsu , Chung Dae Sung , Kim Se Hyun
Published: February 2017

The outstanding electrical, optical, and mechanical properties of silver nanowire transparent electrodes are attractive for use in many optoelectronic devices, and the recent developments related to these electrodes have led to their commercialization. To more fully utilize the advantages of this technology, developing new process technologies in addition to performance improvements is important. In this report, we propose a novel ultra-simple patterning technology to generate a silver nanowire transparent layer and a unique patterned structure with continuously distributed silver nanowires without any etched areas. The patterning is conducted by exposure to ultraviolet light and rinsing. The exposed and unexposed regions of the resulting layer have dramatically different electrical conductivities, which produces an electrical pathway without using any etching or lift-off processes. The unique patterned structure produced by this etching-free method creates hardly any optical difference between the two regions and results in excellent visibility of the patterned transparent electrode layer.
Ecological risk assessment on heavy metals in soils: Use of soil diffuse reflectance mid-infrared Fourier-transform spectroscopy
Authors: Wang Cheng , Li Wei , Guo Mingxing , Ji Junfeng
Published: February 2017

The bioavailability of heavy metals in soil is controlled by their concentrations and soil properties. Diffuse reflectance mid-infrared Fourier-transform spectroscopy (DRIFTS) is capable of detecting specific organic and inorganic bonds in metal complexes and minerals and therefore, has been employed to predict soil composition and heavy metal contents. The present study explored the potential of DRIFTS for estimating soil heavy metal bioavailability. Soil and corresponding wheat grain samples from the Yangtze River Delta region were analyzed by DRIFTS and chemical methods. Statistical regression analyses were conducted to correlate the soil spectral information to the concentrations of Cd, Cr, Cu, Zn, Pb, Ni, Hg and Fe in wheat grains. The principal components in the spectra influencing soil heavy metal bioavailability were identified and used in prediction model construction. The established soil DRIFTS-based prediction models were applied to estimate the heavy metal concentrations in wheat grains in the mid-Yangtze River Delta area. The predicted heavy metal concentrations of wheat grain were highly consistent with the measured levels by chemical analysis, showing a significant correlation (r2 > 0.72) with acceptable root mean square error RMSE. In conclusion, DRIFTS is a promising technique for assessing the bioavailability of soil heavy metals and related ecological risk.
Paenibacillus polymyxa NSY50 suppresses Fusarium wilt in cucumbers by regulating the rhizospheric microbial community
Authors: Shi Lu , Du Nanshan , Shu Sheng , Sun Jin , Li Shuzhan , Guo Shirong
Published: February 2017

Paenibacillus polymyxa (P. polymyxa) NSY50, isolated from vinegar residue substrate, suppresses the growth of Fusarium oxysporum in the cucumber rhizosphere and protects the host plant from pathogen invasion. The aim of the present study was to evaluate the effects of NSY50 application on cucumber growth, soil properties and composition of the rhizospheric soil microbial community after exposure to Fusarium oxysporum. Bacterial and fungal communities were investigated by Illumina sequencing of the 16S rRNA gene and the internal transcribed spacer (ITS) regions (ITS1 and ITS2). The results showed that NSY50 effectively reduced the incidence of Fusarium wilt (56.4%) by altering the soil physico-chemical properties (e.g., pH, Cmic, Rmic, total N and Corg) and enzyme activities, especially of urease and β-glucosidase, which were significantly increased by 2.25- and 2.64-fold, respectively, relative to the pathogen treatment condition. More specifically, NSY50 application reduced the abundance of Fusarium and promoted potentially beneficial groups, including the Bacillus, Actinobacteria, Streptomyces, Actinospica, Catenulispora and Pseudomonas genera. Thus, our results suggest that NSY50 application can improve soil properties, shift the microbial community by increasing beneficial strains and decreasing pathogen colonization in the cucumber rhizosphere, and reduce the occurrence of cucumber Fusarium wilt, thereby promoting cucumber growth.
Correction: Corrigendum: Correlation of p-doping in CVD Graphene with Substrate Surface Charges
Authors: Goniszewski S. , Adabi M. , Shaforost O. , Hanham S. M. , Hao L. , Klein N.
Published: February 2017

Scientific Reports 6: Article number: 22858; published online: 09 March 2016; updated: 13 February 2017 This Article contains errors in Figure 4, where the left (θL) and right (θR) angles are incorrectly defined. The correct Figure 4 appears below as Figure 1.
Pitfalls of invasive blood pressure monitoring using the caudal ventral artery in rats
Authors: Ohta Hiroki , Ohki Takao , Kanaoka Yuji , Koizumi Makoto , Okano Hirotaka J.
Published: February 2017

During rodent experiments, the caudal ventral artery (CVA) is useful for blood pressure (BP) measurement. However, CVA measurements may not reflect the true BP. This study was performed to verify the site-specific accuracy of invasive arterial BP monitoring during surgery in rats. Invasive arterial BP was simultaneously measured in rats via the CVA and the common carotid artery (CCA). The BP values were analysed while the rats were subjected to cooling of the head or tail. Additionally, the rats underwent digital subtraction angiography and histological examination of these arteries. The pressure difference was more significant in the tail cooling group than in the head cooling group. Digital subtraction angiography revealed that angiospasms occurred more frequently in the CVA than in the CCA upon cooling. This phenomenon was supported by histological analysis, which showed that the tunica media area was significantly larger in the CVA than in the CCA. CVA pressure is susceptible to environmental changes and may not accurately reflect the true BP without a strictly controlled laboratory environment. Therefore, understanding the pitfalls of this method is necessary to avoid cooling of the tail during BP measurement.
Snapshot linear-Stokes imaging spectropolarimeter using division-of-focal-plane polarimetry and integral field spectroscopy
Authors: Mu Tingkui , Pacheco Shaun , Chen Zeyu , Zhang Chunmin , Liang Rongguang
Published: February 2017

In this paper, the design and experimental demonstration of a snapshot linear-Stokes imaging spectropolarimeter (SLSIS) is presented. The SLSIS, which is based on division-of-focal-plane polarimetry with four parallel linear polarization channels and integral field spectroscopy with numerous slit dispersive paths, has no moving parts and provides video-rate Stokes-vector hyperspectral datacubes. It does not need any scanning in the spectral, spatial or polarization dimension and offers significant advantages of rapid reconstruction without heavy computation during post-processing. The principle and the experimental setup of the SLSIS are described in detail. The image registration, Stokes spectral reconstruction and calibration procedures are included, and the system is validated using measurements of tungsten light and a static scene. The SLSIS’s snapshot ability to resolve polarization spectral signatures is demonstrated using measurements of a dynamic scene.
Polarisers in the focal domain: Theoretical model and experimental validation
Authors: Martínez-Herrero Rosario , Maluenda David , Juvells Ignasi , Carnicer Artur
Published: February 2017

Polarisers are one of the most widely used devices in optical set-ups. They are commonly used with paraxial beams that propagate in the normal direction of the polariser plane. Nevertheless, the conventional projection character of these devices may change when the beam impinges a polariser with a certain angle of incidence. This effect is more noticeable if polarisers are used in optical systems with a high numerical aperture, because multiple angles of incidence have to be taken into account. Moreover, the non-transverse character of highly focused beams makes the problem more complex and strictly speaking, the Malus’ law does not apply. In this paper we develop a theoretical framework to explain how ideal polarisers affect the behavior of highly focused fields. In this model, the polarisers are considered as birefringent plates, and the vector behaviour of focused fields is described using the plane-wave angular spectrum approach. Experiments involving focused fields were conducted to verify the theoretical model and a satisfactory agreement between theoretical and experimental results was found.
Reference genes for quantitative real-time PCR analysis in symbiont Entomomyces delphacidicola of Nilaparvata lugens (Stål)
Authors: Wan Pin-Jun , Tang Yao-Hua , Yuan San-Yue , He Jia-Chun , Wang Wei-Xia , Lai Feng-Xiang , Fu Qiang
Published: February 2017

Nilaparvata lugens (Stål) (Hemiptera: Delphacidae) is a major rice pest that harbors an endosymbiont ascomycete fungus, Entomomyces delphacidicola str. NLU (also known as yeast-like symbiont, YLS). Driving by demand of novel population management tactics (e.g. RNAi), the importance of YLS has been studied and revealed, which greatly boosts the interest of molecular level studies related to YLS. The current study focuses on reference genes for RT-qPCR studies related to YLS. Eight previously unreported YLS genes were cloned, and their expressions were evaluated for N. lugens samples of different developmental stages and sexes, and under different nutritional conditions and temperatures. Expression stabilities were analyzed by BestKeeper, geNorm, NormFinder, ΔCt method and RefFinder. Furthermore, the selected reference genes for RT-qPCR of YLS genes were validated using targeted YLS genes that respond to different nutritional conditions (amino acid deprivation) and RNAi. The results suggest that ylsRPS15p/ylsACT are the most suitable reference genes for temporal gene expression profiling, while ylsTUB/ylsACT and ylsRPS15e/ylsGADPH are the most suitable reference gene choices for evaluating nutrition and temperature effects. Validation studies demonstrated the advantage of using endogenous YLS reference genes for YLS studies.
β-Thalassemia Patients Revealed a Significant Change of Untargeted Metabolites in Comparison to Healthy Individuals
Authors: Musharraf Syed Ghulam , Iqbal Ayesha , Ansari Saqib Hussain , Parveen Sadia , Khan Ishtiaq Ahmad , Siddiqui Amna Jabbar
Published: February 2017

β-Thalassemia is one of the most prevalent forms of congenital blood disorders characterized by reduced hemoglobin levels with severe complications, affecting all dimensions of life. The mechanisms underlying the phenotypic heterogeneity of β-thalassemia are still poorly understood. We aimed to work over metabolite biomarkers to improve mechanistic understanding of phenotypic heterogeneity and hence better management of disorder at different levels. Untargeted serum metabolites were analyzed after protein precipitation and SPE (solid phase extraction) from 100 β-thalassemia patients and 61 healthy controls using GC-MS. 40 metabolites were identified having a significance difference between these two groups at probability of 0.05 and fold change >1.5. Out of these 40 metabolites, 17 were up-regulated while 23 were down-regulated. PCA and PLS-DA model was also created that revealed a fine separation with a sensitivity of 70% and specificity of 100% on external validation of samples. Metabolic pathway analysis revealed alteration in multiple pathways including glycolysis, pyruvate, propanoate, glycerophospholipid, galactose, fatty acid, starch and sucrose metabolism along with fatty acid elongation in mitochondria, glycerolipid, glyoxylate and dicarboxylate metabolism pointing towards the shift of metabolism in β-thalassemia patients in comparison to healthy individuals.
Beat-to-Beat Blood Pressure and Two-dimensional (axial and radial) Motion of the Carotid Artery Wall: Physiological Evaluation of Arterial Stiffness
Authors: Xu Chenchu , Xiong Huahua , Gao Zhifan , Liu Xin , Zhang Heye , Zhang Yanping , Du Xiuquan , Wu Wanqing , Liu Guotao , Li Shuo
Published: February 2017

The physiological relationship between local arterial displacement and blood pressure (BP) plays an integral role in assess- ment of the mechanical properties of arteries. In this study, we used more advanced methods to obtain reliable continuous BP and the displacement of the common carotid artery (CCA) simultaneously. We propose a novel evaluation method for arterial stiffness that relies on determining the physiological relationship between the axial and radial displacements of the CCA wall and beat-to-beat BP. Patients (total of 138) were divided into groups according to the following three criteria: essential hyper- tension (EH) and normotension, male and female, elderly and younger. The Pearson correlation test and canonical correlation analysis showed that the CCA indices were significantly correlated with BP indices (r = 0:787;p < 0:05). The slope of the CCA displacement/pressure curve showed a progressive reduction with increasing age and EH disease occurrence (EH: 0.496 vs. normotension: 0.822;age <= 60:0.585 vs.age > 60:0.783). Our method provides an explicit reference value and relationship for the manner in which the CCA wall responds to changes in BP. Short-term and continuous BP were significantly correlated with CCA displacement and exhibited a close inverse relationship with each subject’s BP and EH, age, and systolic blood pressure.
Round-robin differential-phase-shift quantum key distribution with a passive decoy state method
Authors: Liu Li , Guo Fen-Zhuo , Qin Su-Juan , Wen Qiao-Yan
Published: February 2017

Recently, a new type of protocol named Round-robin differential-phase-shift quantum key distribution (RRDPS QKD) was proposed, where the security can be guaranteed without monitoring conventional signal disturbances. The active decoy state method can be used in this protocol to overcome the imperfections of the source. But, it may lead to side channel attacks and break the security of QKD systems. In this paper, we apply the passive decoy state method to the RRDPS QKD protocol. Not only can the more environment disturbance be tolerated, but in addition it can overcome side channel attacks on the sources. Importantly, we derive a new key generation rate formula for our RRDPS protocol using passive decoy states and enhance the key generation rate. We also compare the performance of our RRDPS QKD to that using the active decoy state method and the original RRDPS QKD without any decoy states. From numerical simulations, the performance improvement of the RRDPS QKD by our new method can be seen.
Linking gene expression to productivity to unravel long- and short-term responses of seagrasses exposed to CO2 in volcanic vents
Authors: Olivé Irene , Silva João , Lauritano Chiara , Costa Monya M. , Ruocco Miriam , Procaccini Gabriele , Santos Rui
Published: February 2017

Ocean acidification is a major threat for marine life but seagrasses are expected to benefit from high CO2.In situ(long-term) and transplanted (short-term) plant incubations of the seagrassCymodocea nodosawere performed near and away the influence of volcanic CO2vents at Vulcano Island to test the hypothesis of beneficial effects of CO2on plant productivity. We relate, for the first time, the expression of photosynthetic, antioxidant and metal detoxification-related genes to net plant productivity (NPP). Results revealed a consistent pattern between gene expression and productivity indicating water origin as the main source of variability. However, the hypothesised beneficial effect of high CO2around vents was not supported. We observed a consistent long- and short-term pattern of gene down-regulation and 2.5-fold NPP decrease in plants incubated in water from the vents and a generalized up-regulation and NPP increase in plants from the vent site incubated with water from the Reference site. Contrastingly, NPP of specimens experimentally exposed to a CO2range significantly correlated with CO2availability. The down-regulation of metal-related genes inC. nodosaleaves exposed to water from the venting site suggests that other factors than heavy metals, may be at play at Vulcano confounding the CO2effects.
The selective flow of volatile organic compounds in conductive polymer-coated microchannels
Authors: Hossein-Babaei Faramarz , Hooshyar Zare Ali
Published: February 2017

Many gaseous markers of critical biological, physicochemical, or industrial occurrences are masked by the cross-sensitivity of the sensors to the other active components present at higher concentrations. Here, we report the strongly selective diffusion and drift of contaminant molecules in air-filled conductive polymer-coated microfluidic channels for the first time. Monitoring the passage of different target molecules through microchannels coated with Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) revealed that contaminants such as hexane, benzene, and CO pass through the channel unaffected by the coating while methanol, ethanol, and partly acetone are blocked. The observations are explained with reference to the selective interactions between the conductive polymer surface and target gas molecules amplified by the large wall/volume ratio in microchannels. The accumulated quantitative data point at the hydrogen bonding as the mechanism of wall adsorption; dipole-dipole interactions are relatively insignificant. The presented model facilitates a better understanding of how the conductive polymer-based chemical sensors operate.
Proteins analysed as virtual knots
Authors: Alexander Keith , Taylor Alexander J. , Dennis Mark R.
Published: February 2017

Long, flexible physical filaments are naturally tangled and knotted, from macroscopic string down to long-chain molecules. The existence of knotting in a filament naturally affects its configuration and properties, and may be very stable or disappear rapidly under manipulation and interaction. Knotting has been previously identified in protein backbone chains, for which these mechanical constraints are of fundamental importance to their molecular functionality, despite their being open curves in which the knots are not mathematically well defined; knotting can only be identified by closing the termini of the chain somehow. We introduce a new method for resolving knotting in open curves using virtual knots, which are a wider class of topological objects that do not require a classical closure and so naturally capture the topological ambiguity inherent in open curves. We describe the results of analysing proteins in the Protein Data Bank by this new scheme, recovering and extending previous knotting results, and identifying topological interest in some new cases. The statistics of virtual knots in protein chains are compared with those of open random walks and Hamiltonian subchains on cubic lattices, identifying a regime of open curves in which the virtual knotting description is likely to be important.
HRGFish: A database of hypoxia responsive genes in fishes
Authors: Rashid Iliyas , Nagpure Naresh Sahebrao , Srivastava Prachi , Kumar Ravindra , Pathak Ajey Kumar , Singh Mahender , Kushwaha Basdeo
Published: February 2017

Several studies have highlighted the changes in the gene expression due to the hypoxia response in fishes, but the systematic organization of the information and the analytical platform for such genes are lacking. In the present study, an attempt was made to develop a database of hypoxia responsive genes in fishes (HRGFish), integrated with analytical tools, using LAMPP technology. Genes reported in hypoxia response for fishes were compiled through literature survey and the database presently covers 818 gene sequences and 35 gene types from 38 fishes. The upstream fragments (3,000 bp), covered in this database, enables to compute CG dinucleotides frequencies, motif finding of the hypoxia response element, identification of CpG island and mapping with the reference promoter of zebrafish. The database also includes functional annotation of genes and provides tools for analyzing sequences and designing primers for selected gene fragments. This may be the first database on the hypoxia response genes in fishes that provides a workbench to the scientific community involved in studying the evolution and ecological adaptation of the fish species in relation to hypoxia.
Rapid differentiation of human pluripotent stem cells into functional neurons by mRNAs encoding transcription factors
Authors: Goparaju Sravan Kumar , Kohda Kazuhisa , Ibata Keiji , Soma Atsumi , Nakatake Yukhi , Akiyama Tomohiko , Wakabayashi Shunichi , Matsushita Misako , Sakota Miki , Kimura Hiromi , Yuzaki Michisuke , Ko Shigeru B. H. , Ko Minoru S. H.
Published: February 2017

Efficient differentiation of human pluripotent stem cells (hPSCs) into neurons is paramount for disease modeling, drug screening, and cell transplantation therapy in regenerative medicine. In this manuscript, we report the capability of five transcription factors (TFs) toward this aim: NEUROG1, NEUROG2, NEUROG3, NEUROD1, and NEUROD2. In contrast to previous methods that have shortcomings in their speed and efficiency, a cocktail of these TFs as synthetic mRNAs can differentiate hPSCs into neurons in 7 days, judged by calcium imaging and electrophysiology. They exhibit motor neuron phenotypes based on immunostaining. These results indicate the establishment of a novel method for rapid, efficient, and footprint-free differentiation of functional neurons from hPSCs.
System-wide detection of protein-small molecule complexes suggests extensive metabolite regulation in plants
Authors: Veyel Daniel , Kierszniowska Sylwia , Kosmacz Monika , Sokolowska Ewelina Maria , Michaelis Aenne , Luzarowski Marcin , Szlachetko Jagoda , Willmitzer Lothar , Skirycz Aleksandra
Published: February 2017

Protein small molecule interactions are at the core of cell regulation controlling metabolism and development. We reasoned that due to the lack of system wide approaches only a minority of those regulatory molecules are known. In order to see whether or not this assumption is true we developed an effective approach for the identification of small molecules having potential regulatory role that obviates the need of protein or small molecule baits. At the core of this approach is a simple biochemical co-fractionation taking advantage of size differences between proteins and small molecules. Metabolomics based analysis of small molecules co-fractionating with proteins identified a multitude of small molecules in Arabidopsis suggesting the existence of numerous, small molecules/metabolites bound to proteins representing potential regulatory molecules. The approach presented here uses Arabidopsis cell cultures, but is generic and hence applicable to all biological systems.
Testicular activin and follistatin levels are elevated during the course of experimental autoimmune epididymo–orchitis in mice
Authors: Nicolas Nour , Michel Vera , Bhushan Sudhanshu , Wahle Eva , Hayward Susan , Ludlow Helen , de Kretser David M. , Loveland Kate L. , Schuppe Hans-Christian , Meinhardt Andreas , Hedger Mark P. , Fijak Monika
Published: February 2017

Experimental autoimmune epididymo-orchitis (EAEO) is a model of chronic inflammation, induced by immunisation with testicular antigens, which reproduces the pathology of some types of human infertility. Activins A and B regulate spermatogenesis and steroidogenesis, but are also pro-inflammatory, pro-fibrotic cytokines. Expression of the activins and their endogenous antagonists, inhibin and follistatin, was examined in murine EAEO. Adult untreated and adjuvant-treated control mice showed no pathology. All mice immunised with testis antigens developed EAEO by 50 days, characterised by loss of germ cells, immune cell infiltration and fibrosis in the testis, similar to biopsies from human inflamed testis. An increase of total CD45+ leukocytes, comprising CD3+ T cells, CD4 + CD8− and CD4 + CD25+ T cells, and a novel population of CD4 + CD8+ double positive T cells was also detected in EAEO testes. This was accompanied by increased expression of TNF, MCP-1 and IL-10. Activin A and B and follistatin protein levels were elevated in EAEO testes, with peak activin expression during the active phase of the disease, whereas mRNA expression of the inhibin B subunits (InhaandInhbb) and activin receptor subunits (Acvr1bandAcvr2b) were downregulated. These data suggest that activin–follistatin regulation may play a role during the development of EAEO.
Interleukin-33 produced by M2 macrophages and other immune cells contributes to Th2 immune reaction of IgG4-related disease
Authors: Furukawa Sachiko , Moriyama Masafumi , Miyake Kensuke , Nakashima Hitoshi , Tanaka Akihiko , Maehara Takashi , Iizuka-Koga Mana , Tsuboi Hiroto , Hayashida Jun-Nosuke , Ishiguro Noriko , Yamauchi Masaki , Sumida Takayuki , Nakamura Seiji
Published: February 2017

IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and marked infiltration of IgG4-positive cells in multiple organs. Interleukin-33 (IL-33) is a recently described cytokine that is secreted by damaged epithelial cells, macrophages, and dendritic cells, and potently activates helper T type 2 (Th2) immune responses, which have been suggested to play a major role in IgG4 production of IgG4-RD. Here, we assessed the expression of IL-33 and related molecules in the salivary glands (SGs) of patients with IgG4-RD versus that in patients with Sjögren’s syndrome (SS) and controls. Expression of IL-33 and its receptor (ST2) was strongly detected around ectopic germinal centers (GCs) in the SGs from patients with IgG4-RD, whereas IL-33 was expressed only in epithelial cells in patients with SS and controls. Moreover, IL-33 and CD68+/CD163+ macrophages were mainly distributed around ectopic GCs in patients with IgG4-RD. Double immunofluorescence staining showed that IL-33 expression co-localized with CD68+/CD163+ macrophages. Finally, mRNA expression levels of IL-33 showed a positive correlation to those of Th2 cytokines (IL-4 and IL-13) in patients with IgG4-RD. Our data suggest that IL-33 produced by M2 macrophages might contribute to the pathogenesis of IgG4-RD via aberrant activation of Th2 immune responses.
Antifouling potential of Nature-inspired sulfated compounds
Authors: Almeida Joana R. , Correia-da-Silva Marta , Sousa Emília , Antunes Jorge , Pinto Madalena , Vasconcelos Vitor , Cunha Isabel
Published: February 2017

Natural products with a sulfated scaffold have emerged as antifouling agents with low or nontoxic effects to the environment. In this study 13 sulfated polyphenols were synthesized and tested for antifouling potential using the anti-settlement activity of mussel (Mytilus galloprovincialis) plantigrade post-larvae and bacterial growth inhibition towards four biofilm-forming bacterial strains. Results show that some of these Nature-inspired compounds were bioactive, particularly rutin persulfate (2), 3,6-bis(β-D-glucopyranosyl) xanthone persulfate (6), and gallic acid persulfate (12) against the settlement of plantigrades. The chemical precursors of sulfated compounds 2 and 12 were also tested for anti-settlement activity and it was possible to conclude that bioactivity is associated with sulfation. While compound 12 showed the most promising anti-settlement activity (EC50 = 8.95 μg.mL−1), compound 2 also caused the higher level of growth inhibition in bacteria Vibrio harveyi (EC20 = 12.5 μg.mL−1). All the three bioactive compounds 2, 6, and 12 were also found to be nontoxic to the non target species Artemia salina (<10% mortality at 250 μM) and Vibrio fischeri (LC50 > 1000 μg.mL−1). This study put forward the relevance of synthesizing non-natural sulfated small molecules to generate new nontoxic antifouling agents.
Flavichalasines A–M, cytochalasan alkaloids from Aspergillus flavipes
Authors: Wei Guangzheng , Tan Dongdong , Chen Chunmei , Tong Qingyi , Li Xiao-Nian , Huang Jinfeng , Liu Junjun , Xue Yongbo , Wang Jianping , Luo Zengwei , Zhu Hucheng , Zhang Yonghui
Published: February 2017

Two new tetracyclic cytochalasans, flavichalasines A and B (1 and 2), three new pentacyclic cytochalasans, flavichalasines C–E (3–5), and eight new tricyclic cytochalasans, flavichalasines F–M (6–13), together with eight known analogues (14–21), were isolated from the solid culture of Aspergillus flavipes. Structures of these new compounds were elucidated on the basis of extensive spectroscopic analyses including 1D, 2D NMR and HRESIMS data. Their absolute configurations were determined by comparison of their experimental ECD with either computed ECD or experimental ECD spectrum of known compound. The structure and absolute configuration of 2 were further determined by X-ray crystallographic diffraction. Flavichalasine A (1) represents the first example of cytochalasan with a terminal double bond at the macrocyclic ring and flavichalasine E (5) is the only cytochalasan with an α-oriented oxygen-bridge in D ring. These new compounds were evaluated for their cytotoxic activities against seven human cancer cell lines, of which, 6 and 14 displayed moderate inhibitory activities against tested cell lines. In addition, compounds 6 and 14 induced apoptosis of HL60 cells by activation of caspase-3 and degradation of PARP.
Accelerated biodegradation of silk sutures through matrix metalloproteinase activation by incorporating 4-hexylresorcinol
Authors: Jo You-Young , Kweon HaeYong , Kim Dae-Won , Kim Min-Keun , Kim Seong-Gon , Kim Jwa-Young , Chae Weon-Sik , Hong Sam-Pyo , Park Young-Hwan , Lee Si Young , Choi Je-Yong
Published: February 2017

Silk suture material is primarily composed of silk fibroin and regarded as a non-resorbable material. It is slowly degraded by proteolysis when it is implanted into the body. 4-Hexylresorcinol (4HR) is a well-known antiseptic. In this study, the biodegradability of 4HR-incorporated silk sutures were compared to that of untreated silk sutures and polyglactin 910 sutures, a commercially available resorbable suture. 4HR-incorporated silk sutures exhibited anti-microbial properties. Matrix metalloproteinase (MMP) can digest a wide spectrum of proteins. 4HR increased MMP-2, -3, and -9 expression in RAW264.7 cells. MMP-2, -3, and -9 were able to digest not only silk fibroin but also silk sutures. Consequently, 59.5% of the 4HR-incorporated silk suture material remained at 11 weeks after grafting, which was similar to that of polyglactin 910 degradation (56.4% remained). The residual amount of bare silk suture material at 11 weeks after grafting was 91.5%. The expression levels of MMP-2, -3 and -9 were high in the 4HR-incorporated silk suture-implanted site 12 weeks after implantation. In conclusion, 4HR-treated silk sutures exhibited anti-microbial properties and a similar level of bio-degradation to polyglactin 910 sutures and induced higher expression of MMP-2, -3, and -9 in macrophages.
Profound seasonal shrinking and regrowth of the ossified braincase in phylogenetically distant mammals with similar life histories
Authors: Dechmann Dina K. N. , LaPoint Scott , Dullin Christian , Hertel Moritz , Taylor Jan R. E. , Zub Karol , Wikelski Martin
Published: February 2017

Ontogenetic changes in skull shape and size are ubiquitous in altricial vertebrates, but typically unidirectional and minimal in full-grown animals. Red-toothed shrews exhibit a rare exception, where the shape, mass and size of the skull, brain, and several major organs, show significant bidirectional seasonal changes. We now show a similar but male-biased shrinking (16%) and regrowth (8%) in the standardized braincase depth of least weasels (Mustela nivalis). Juvenile weasels also exhibit a growth overshoot, followed by a shrinkage period lasting until the end of their first winter. Only male weasels then regrow during their second summer. High-resolution CT scans suggest areas of the skull are affected differently during shrinking and regrowth in both species. This suggests multiple evolutionary drivers: while the shrinking likely facilitates survival during seasonal low resource availability in these high-metabolic mammals with year-round activity, the regrowth may be most strongly influenced by high investment into reproduction and territories, which is male-biased in the weasels. Our data provide evidence for convergent evolution of skull and thus brain shrinkage and regrowth, with important implications for understanding adaptations to changing environments and for applied research on the correlated changes in bone structure, brain size and the many other affected organs.
Boosting laser-ion acceleration with multi-picosecond pulses
Authors: Yogo A. , Mima K. , Iwata N. , Tosaki S. , Morace A. , Arikawa Y. , Fujioka S. , Johzaki T. , Sentoku Y. , Nishimura H. , Sagisaka A. , Matsuo K. , Kamitsukasa N. , Kojima S. , Nagatomo H. , Nakai M. , Shiraga H. , Murakami M. , Tokita S. , Kawanaka J. , Miyanaga N. , Yamanoi K. , Norimatsu T. , Sakagami H. , Bulanov S. V. , Kondo K. , Azechi H.
Published: February 2017

Using one of the world most powerful laser facility, we demonstrate for the first time that high-contrast multi-picosecond pulses are advantageous for proton acceleration. By extending the pulse duration from 1.5 to 6 ps with fixed laser intensity of 1018 W cm−2, the maximum proton energy is improved more than twice (from 13 to 33 MeV). At the same time, laser-energy conversion efficiency into the MeV protons is enhanced with an order of magnitude, achieving 5% for protons above 6 MeV with the 6 ps pulse duration. The proton energies observed are discussed using a plasma expansion model newly developed that takes the electron temperature evolution beyond the ponderomotive energy in the over picoseconds interaction into account. The present results are quite encouraging for realizing ion-driven fast ignition and novel ion beamlines.