bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptation of influenza A (H7N9) virus in primary human airway epithelial cells
Authors: Huang Daniel Tsung-Ning , Lu Chun-Yi , Chi Ya-Hui , Li Wan-Ling , Chang Luan-Yin , Lai Mei-Ju , Chen Jin-Shing , Hsu Wen-Ming , Huang Li-Min
Published: September 2017

Influenza A (H7N9) is an emerging zoonotic pathogen with pandemic potential. To understand its adaptation capability, we examined the genetic changes and cellular responses following serial infections of A (H7N9) in primary human airway epithelial cells (hAECs). After 35 serial passages, six amino acid mutations were found, i.e. HA (R54G, T160A, Q226L, H3 numbering), NA (K289R, or K292R for N2 numbering), NP (V363V/I) and PB2 (L/R332R). The mutations in HA enabled A(H7N9) virus to bind with higher affinity (from 39.2% to 53.4%) to sialic acid α2,6-galactose (SAα2,6-Gal) linked receptors. A greater production of proinflammatory cytokines in hAECs was elicited at later passages together with earlier peaking at 24 hours post infection of IL-6, MIP-1α, and MCP-1 levels. Viral replication capacity in hAECs maintained at similar levels throughout the 35 passages. In conclusion, during the serial infections of hAECs by influenza A(H7N9) virus, enhanced binding of virion to cell receptors with subsequent stronger innate cell response were noted, but no enhancement of viral replication could be observed. This indicates the existence of possible evolutional hurdle for influenza A(H7N9) virus to transmit efficiently from human to human.
Physicochemical stability and transfection efficiency of cationic amphiphilic copolymer/pDNA polyplexes for spinal cord injury repair
Authors: Gwak So-Jung , Macks Christian , Bae Sooneon , Cecil Noah , Lee Jeoung Soo
Published: September 2017

Multiple age-related and injury-induced characteristics of the adult central nervous system (CNS) pose barriers to axonal regeneration and functional recovery following injury. In situ gene therapy is a promising approach to address the limited availability of growth-promoting biomolecules at CNS injury sites. The ultimate goal of our work is to develop, a cationic amphiphilic copolymer for simultaneous delivery of drug and therapeutic nucleic acids to promote axonal regeneration and plasticity after spinal cord injury. Previously, we reported the synthesis and characterization of a cationic amphiphilic copolymer, poly (lactide-co-glycolide)-graft-polyethylenimine (PgP) and its ability to efficiently transfect cells with pDNA in the presence of serum. We also demonstrated the efficacy of PgP as a therapeutic siRhoA carrier in a rat compression spinal cord injury model. In this work, we show that PgP/pDNA polyplexes provide improved stability in the presence of competing polyanions and nuclease protection in serum relative to conventional branched polyethylenimine control. PgP/pDNA polyplexes maintain bioactivity for transfection after lyophilization/reconstitution and during storage at 4 °C for up to 5 months, important features for commercial and clinical application. We also demonstrate that PgP/pDNA polyplexes loaded with a hydrophobic fluorescent dye are retained in local neural tissue for up to 5 days and that PgP can efficiently deliver pβ-Gal in a rat compression SCI model.
Differential effects of soluble and aggregating polyQ proteins on cytotoxicity and type-1 myosin-dependent endocytosis in yeast
Authors: Berglund Lisa L. , Hao Xinxin , Liu Beidong , Grantham Julie , Nyström Thomas
Published: September 2017

Huntington’s disease develops when the polyglutamine (polyQ) repeat in the Huntingtin (Htt) protein is expanded to over 35 glutamines rendering it aggregation-prone. Here, using Htt exon-1 as a polyQ model protein in a genome-wide screen in yeast, we show that the normal and soluble Htt exon-1 is toxic in cells with defects in type-1 myosin-dependent endocytosis. The toxicity of Htt is linked to physical interactions with type-1 myosins, which occur via the Htt proline-rich region, leading to a reduction in actin patch polarization and clathrin-dependent endocytosis. An expansion of the polyQ stretch from 25 to 103 glutamines, which causes Htt aggregation, alleviated Htt toxicity in cells lacking Myo5 or other components involved in early endocytosis. The data suggest that the proline-rich stretch of Htt interacts with type-1 myosin/clathrin-dependent processes and demonstrate that a reduction in the activity of such processes may result in a positive selection for polyQ expansions.
5,7-Di-N-acetyl-8-epiacinetaminic acid: A new non-2-ulosonic acid found in the K73 capsule produced by an Acinetobacter baumannii isolate from Singapore
Authors: Kenyon Johanna J. , Notaro Anna , Hsu Li Yang , De Castro Cristina , Hall Ruth M.
Published: September 2017

Nonulosonic acids are found in the surface polysaccharides of many bacterial species and are often implicated in pathogenesis. Here, the structure of a novel 5,7-diacetamido-3,5,7,9-tetradeoxynon-2-ulosonic acid recovered from the capsular polysaccharide of a multiply antibiotic resistant Acinetobacter baumannii isolate was determined. The isolate carries a sugar synthesis module that differs by only a single gene from the module for the synthesis of 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-L-altro-non-2-ulosonic acid or 5,7-di-N-acetylacinetaminic acid, recently discovered in the capsule of another A. baumannii isolate. The new monosaccharide is the C8-epimer of acinetaminic acid (8eAci; 5,7-diacetamido-3,5,7,9-tetradeoxy-D-glycero-L-altro-non-2-ulosonic acid) and the C7-epimer of legionaminic acid. This monosaccharide had not previously been detected in a biological sample but had been synthesized chemically.
Qualitative and quantitative responses to press perturbations in ecological networks
Authors: Giordano Giulia , Altafini Claudio
Published: September 2017

Predicting the sign of press perturbation responses in ecological networks is challenging, due to the poor knowledge of the strength of the direct interactions among the species, and to the entangled coexistence of direct and indirect effects. We show in this paper that, for a class of networks that includes mutualistic and monotone networks, the sign of press perturbation responses can be qualitatively determined based only on the sign pattern of the community matrix, without any knowledge of parameter values. For other classes of networks, we show that a semi-qualitative approach yields sufficient conditions for community matrices with a given sign pattern to exhibit mutualistic responses to press perturbations; quantitative conditions can be provided as well for community matrices that are eventually nonnegative. We also present a computational test that can be applied to any class of networks so as to check whether the sign of the responses to press perturbations is constant in spite of parameter variations.
A bead-assisted flow cytometry method for the semi-quantitative analysis of Extracellular Vesicles
Authors: Suárez Henar , Gámez-Valero Ana , Reyes Raquel , López-Martín Soraya , Rodríguez María Josefa , Carrascosa José L. , Cabañas Carlos , Borràs Francesc E. , Yáñez-Mó María
Published: September 2017

Most experimental approaches commonly employed for the characterization and quantitation of EVs are time consuming, require of specialized instrumentation and often are rather inaccurate. To circumvent the caveats imposed by EV small size, we used general and specific membrane markers in bead assisted flow cytometry, to provide a semi-quantitative measure of EV content in a given sample. EVs were isolated from in vitro cultured cells-conditioned medium and biological fluids by size exclusion chromatography and coupled to latex beads to allow their detection by standard flow cytometers. Our analyses demonstrate a linear correlation between EV concentration and Mean Fluorescence Intensity values in samples cleared of protein contaminants. Comparison with one of the most widespread method such as NTA, suggests a similar linear range and reliable accuracy to detect saturation. However, although detection of the different biomarkers is feasible when tested on ultracentrifugation-enriched samples, protein contamination impairs quantitation of this type of samples by bead-based flow cytometry. Thus, we provide evidence that bead-assisted flow cytometry method is an accurate and reliable method for the semiquantitative bulk analysis of EVs, which could be easily implemented in most laboratories.
Induction of oxidative metabolism by the p38α/MK2 pathway
Authors: Trempolec Natalia , Muñoz Juan Pablo , Slobodnyuk Konstantin , Marin Silvia , Cascante Marta , Zorzano Antonio , Nebreda Angel R.
Published: September 2017

Adequate responses to environmental stresses are essential for cell survival. The regulation of cellular energetics that involves mitochondrial energy production and oxidative stress is central in the process of stress adaptation and response. The p38α signalling pathway plays a key role in the response to stress stimuli by orchestrating multiple cellular processes. However, prolonged activation of the p38α pathway results in impaired cell proliferation and can lead to cell death. Here we use a system to specifically activate p38α signalling and show that sustained activation of this pathway suffices to induce important metabolic changes, including high dependence on glucose for cell survival, increased consumption of glutamine, enhanced respiration rate and elevated production of mitochondrial reactive oxygen species (ROS). Moreover, we provide evidence that increased production of mitochondrial superoxide as a consequence of elevated mitochondria activity, contributes to the p38α reduced cell survival triggered by sustained p38α activation. We also show that the p38α-activated kinase MAPKAPK2 (MK2) plays an important role orchestrating the observed metabolic changes. Our results illustrate a new function of p38α signalling in the regulation of cellular metabolism, which may lead to cell death upon persistent activation of the pathway.
Assessment of T-cell receptor repertoire and clonal expansion in peripheral T-cell lymphoma using RNA-seq data
Authors: Gong Qiang , Wang Chao , Zhang Weiwei , Iqbal Javeed , Hu Yang , Greiner Timothy C. , Cornish Adam , Kim Jo-Heon , Rabadan Raul , Abate Francesco , Wang Xin , Inghirami Giorgio G. , McKeithan Timothy W. , Chan Wing C.
Published: September 2017

T-cell clonality of peripheral T-cell lymphoma (PTCL) is routinely evaluated with a PCR-based method using genomic DNA. However, there are limitations with this approach. The purpose of this study was to determine the utility of RNA-seq for assessing T-cell clonality and T-cell antigen receptor (TCR) repertoire of the neoplastic T-cells in 108 PTCL samples. TCR transcripts, including complementarity-determining region 3 (CDR3) sequences, were assessed. In normal T cells, the CDR3 sequences were extremely diverse, without any clonotype representing more than 2% of the overall TCR population. Dominant clones could be identified in 65 out of 76 PTCL cases (86%) with adequate TCR transcript expression. In monoclonal cases, the dominant clone varied between 11% and 99% of TCRβ transcripts. No unique Vα or Vβ usage was observed. Small T-cell clones were often observed in T- and NK-cell tumors in a percentage higher than observed in reactive conditions. γ chain expression was very low in tumors expressing TCRαβ, but its expression level was high and clonality was detected in a TCRγδ expressing tumor. NK cell lymphoma (NKCL) did not express significant levels of TCR Vβ or Vγ genes. RNA-seq is a useful tool for detecting and characterizing clonal TCR rearrangements in PTCL.
Structure-function correlations in Retinitis Pigmentosa patients with partially preserved vision: a voxel-based morphometry study
Authors: Rita Machado Ana , Carvalho Pereira Andreia , Ferreira Fábio , Ferreira Sónia , Quendera Bruno , Silva Eduardo , Castelo-Branco Miguel
Published: September 2017

Retinitis Pigmentosa is a group of hereditary retinal dystrophy disorders associated with progressive peripheral visual field loss. The impact of this retinal loss in cortical gray matter volume has not been addressed before in Retinitis Pigmentosa patients with low vision. Voxel-based morphometry was applied to study whole brain gray matter volume changes in 27 Retinitis Pigmentosa patients with partially preserved vision and 38 age- and gender-matched normally sighted controls to determine whether peripheral visual loss can lead to changes in gray matter volume. We found significant reductions in gray matter volume that were restricted to the occipital cortex of patients. The anteromedial pattern of reduced gray matter volume in visual primary and association cortices was significantly correlated with the extent of the peripheral visual field deficit in this cohort. Moreover, this pattern was found to be associated with the extent of visual field loss. In summary, we found specific visual cortical gray matter loss in Retinitis Pigmentosa patients associated with their visual function profile. The spatial pattern of gray matter loss is consistent with disuse-driven neuronal atrophy which may have clinical implications for disease management, including prosthetic restoration strategies.
Spatio-temporal and dynamic regulation of neurofascin alternative splicing in mouse cerebellar neurons
Authors: Suzuki Satoko , Ayukawa Noriko , Okada Chisa , Tanaka Masami , Takekoshi Susumu , Iijima Yoko , Iijima Takatoshi
Published: September 2017

Alternative splicing is crucial for molecular diversification, which greatly contributes to the complexity and specificity of neural functions in the central nervous system (CNS). Neurofascin (NF) is a polymorphic cell surface protein that has a number of splicing isoforms. As the alternative splicing of the neurofascin gene (Nfasc) is developmentally regulated, NF isoforms have distinct functions in immature and mature brains. However, the molecular mechanisms underlying the alternative splicing of Nfasc in neurons are not yet understood. Here, we demonstrate that, alongside developmental regulation, Nfasc alternative splicing is spatially controlled in the mouse brain. We then identified distinct Nfasc splicing patterns at the cell-type level in the cerebellum, with Nfasc186 being expressed in Purkinje cells and absent from granule cells (GCs). Furthermore, we show that high K+-induced depolarization triggers a shift in splicing from Nfasc140 to Nfasc186 in cerebellar GCs. Finally, we identified a neural RNA-binding protein, Rbfox, as a key player in neural NF isoform selection, specifically controlling splicing at exons 26−29. Together, our results show that Nfasc alternative splicing is spatio-temporally and dynamically regulated in cerebellar neurons. Our findings provide profound insight into the mechanisms underlying the functional diversity of neuronal cell-adhesive proteins in the mammalian CNS.
Effects of protease-treated royal jelly on muscle strength in elderly nursing home residents: A randomized, double-blind, placebo-controlled, dose-response study
Authors: Meng Ge , Wang Honglei , Pei Yinghua , Li Yanmei , Wu Hongmei , Song Yanqi , Guo Qi , Guo Hui , Fukushima Shinobu , Tatefuji Tomoki , Wang Jiazhong , Du Huanmin , Su Qian , Zhang Wen , Shen Suxing , Wang Xiuyang , Dong Renwei , Han Peipei , Okazaki Tatsuma , Nagatomi Ryoichi , Wang Jianhua , Huang Guowei , Sun Zhong , Song Kun , Niu Kaijun
Published: September 2017

Although we have found that protease-treated royal jelly (pRJ) benefit for the skeletal muscle mass and strength in the aged animals, the potential beneficial effects have not been evaluated in humans. The aim of this study was to determine whether pRJ intake had beneficial effects on muscle strength in elderly nursing home residents. One hundred and ninety-four subjects enrolled into this multicenter, randomized, double-blind, placebo-controlled study. Subjects received either placebo(Group 1), pRJ 1.2 g/d(Group 2), or 4.8 g/d(Group 3). Data through 1 year are reported for 163 subjects. The primary outcome measure is handgrip strength. Secondary outcomes include several physical performance tests (six-minute walk test, timed up and go test, and standing on one leg with eyes closed). The dropout rate was 16.0%. The means (95% confidence interval) of change in handgrip strength for placebo, low-dose, and high-dose groups are −0.98(−2.04,0.08), 0.50(−0.65,1.65) and 1.03(−0.37,2.44) kg (P = 0.06, P for trend = 0.02), respectively. No significant effects of the interventions were observed for physical performances. These findings suggest that pRJ treatment might not improve, but rather attenuate the progression of decrease in muscle strength in elderly people. In addition, we have not found that pRJ intervention can achieve improvement or attenuating the decrease in physical performance.
High throughput data analyses of the immune characteristics of Microtus fortis infected with Schistosoma japonicum
Authors: Hu Yuan , Sun Lei , Yuan Zhongying , Xu Yuxin , Cao Jianping
Published: September 2017

Microtus fortis exhibits natural resistance against Schistosoma japonicum, and the parasite cannot grow and develop in M. fortis. Extensive research has been carried out, however, the associated mechanism remains unclear. In the present study, we analysed the combined data obtained from a cytokine chip assay, transcriptome, and metabolome. The cytokine profile from C57BL/6 and M. fortis mice was assessed before and after infection. Several cytokines increased during the second and third week post-infection. Some transcripts related to cytokine genes and associated proteins were also highly expressed (i.e., Hgf, C3, and Lbp). The liver metabolism of M. fortis following infection with S. japonicum was assessed. We identified 25 different metabolites between the uninfected and infected M. fortis, and 22 different metabolites between infected M. fortis and C57BL/6 mice. The metabolomic pathways of these differential metabolites were then analysed with MetPA, revealing that they were involved in histidine metabolism, valine, leucine, and isoleucine biosyntheses, and lysine degradation. Thus, the elevated expression of these metabolites and pathways may promote the phagocytic function of the neutrophils and natural killer cell activity following TLR activation. These results provide novel insight into the resistance mechanism of M. fortis against S. japonicum.
Subtle shifts in microbial communities occur alongside the release of carbon induced by drought and rewetting in contrasting peatland ecosystems
Authors: Potter Caitlin , Freeman Chris , Golyshin Peter N. , Ackermann Gail , Fenner Nathalie , McDonald James E. , Ehbair Abdassalam , Jones Timothy G. , Murphy Loretta M. , Creer Simon
Published: September 2017

Peat represents a globally significant pool of sequestered carbon. However, peatland carbon stocks are highly threatened by anthropogenic climate change, including drought, which leads to a large release of carbon dioxide. Although the enzymatic mechanisms underlying drought-driven carbon release are well documented, the effect of drought on peatland microbial communities has been little studied. Here, we carried out a replicated and controlled drought manipulation using intact peat ‘mesocosm cores’ taken from bog and fen habitats, and used a combination of community fingerprinting and sequencing of marker genes to identify community changes associated with drought. Community composition varied with habitat and depth. Moreover, community differences between mesocosm cores were stronger than the effect of the drought treatment, emphasising the importance of replication in microbial marker gene studies. While the effect of drought on the overall composition of prokaryotic and eukaryotic communities was weak, a subset of the microbial community did change in relative abundance, especially in the fen habitat at 5 cm depth. ‘Drought-responsive’ OTUs were disproportionately drawn from the phyla Bacteroidetes and Proteobacteria. Collectively, the data provide insights into the microbial community changes occurring alongside drought-driven carbon release from peatlands, and suggest a number of novel avenues for future research.
Limitations of Qdot labelling compared to directly-conjugated probes for single particle tracking of B cell receptor mobility
Authors: Abraham Libin , Lu Henry Y. , Falcão Rebeca Cardim , Scurll Joshua , Jou Timothy , Irwin Brian , Tafteh Reza , Gold Michael R. , Coombs Daniel
Published: September 2017

Single-particle tracking (SPT) is a powerful method for exploring single-molecule dynamics in living cells with nanoscale spatiotemporal resolution. Photostability and bright fluorescence make quantum dots (Qdots) a popular choice for SPT. However, their large size could potentially alter the mobility of the molecule of interest. To test this, we labelled B cell receptors on the surface of B-lymphocytes with monovalent Fab fragments of antibodies that were either linked to Qdots via streptavidin or directly conjugated to the small organic fluorophore Cy3. Imaging of receptor mobility by total internal reflection fluorescence microscopy (TIRFM), followed by quantitative single-molecule diffusion and confinement analysis, definitively showed that Qdots sterically hinder lateral mobility regardless of the substrate to which the cells were adhered. Qdot labelling also drastically altered the frequency with which receptors transitioned between apparent slow- and fast-moving states and reduced the size of apparent confinement zones. Although we show that Qdot-labelled probes can detect large differences in receptor mobility, they fail to resolve subtle differences in lateral diffusion that are readily detectable using Cy3-labelled Fabs. Our findings highlight the utility and limitations of using Qdots for TIRFM and wide-field-based SPT, and have significant implications for interpreting SPT data.
ApoE4-associated phospholipid dysregulation contributes to development of Tau hyper-phosphorylation after traumatic brain injury
Authors: Cao Jiqing , Gaamouch Farida El , Meabon James S. , Meeker Kole D. , Zhu Li , Zhong Margaret B. , Bendik John , Elder Gregory , Jing Ping , Xia Jiahong , Luo Wenjie , Cook David G. , Cai Dongming
Published: September 2017

The apolipoprotein E4 (ApoE4) genotype combines with traumatic brain injury (TBI) to increase the risk of developing Alzheimer’s Disease (AD). However, the underlying mechanism(s) is not well-understood. We found that after exposure to repetitive blast-induced TBI, phosphoinositol biphosphate (PIP2) levels in hippocampal regions of young ApoE3 mice were elevated and associated with reduction in expression of a PIP2 degrading enzyme, synaptojanin 1 (synj1). In contrast, hippocampal PIP2 levels in ApoE4 mice did not increase after blast TBI. Following blast TBI, phospho-Tau (pTau) levels were unchanged in ApoE3 mice, whereas in ApoE4 mice, levels of pTau were significantly increased. To determine the causal relationship between changes in pTau and PIP2/synj1 levels after TBI, we tested if down-regulation of synj1 prevented blast-induced Tau hyper-phosphorylation. Knockdown of synj1 decreased pTau levels in vitro, and abolished blast-induced elevation of pTau in vivo. Blast TBI increased glycogen synthase kinase (GSK)-3β activities in ApoE4 mice, and synj1 knockdown inhibited GSK3β phosphorylation of Tau. Together, these data suggest that ApoE proteins regulate brain phospholipid homeostasis in response to TBI and that the ApoE4 isoform is dysfunctional in this process. Down-regulation of synj1 rescues blast-induced phospholipid dysregulation and prevents development of Tau hyper-phosphorylation in ApoE4 carriers.
The controllable destabilization route for synthesis of low cytotoxic magnetic nanospheres with photonic response
Authors: Andreeva Yulia I. , Drozdov Andrey S. , Fakhardo Anna F. , Cheplagin Nikolay A. , Shtil Alexander A. , Vinogradov Vladimir V.
Published: September 2017

We present a new approach for obtaining magnetic nanospheres with tunable size and high magnetization. The method is implemented via controllable destabilization of a stable magnetite hydrosol with glycerol, leading to the formation of aggregates followed by their stabilization with the citrate shell. This inexpensive, simple and easily scalable approach required no special equipment. The obtained samples were characterized by high stability and magnetization over 80 emu/g. Effects of synthetic conditions on physicochemical properties of nanospheres were monitored by hydrodynamic size, zeta potential, and polydispersity of magnetite aggregates. The size of the resulting aggregates varied between 650 nm and 40 nm, and the zeta potential from +30 mV to −43 mV by changing the ratio of the reagents. Under optimal conditions the clusters with a diameter of 80 nm were produced with a narrow size distribution ±3 nm. These characteristics allowed for optical response to the external magnetic field, thereby producing a magnetic photon liquid. Due to biocompatibility of the reagents used in the synthesis the nanospheres evoked a negligible cytotoxicity for human non-malignant and tumor cell lines. These results make new materials valuable in photonics and biomedicine.
Synchrotron-based ν-XRF mapping and μ-FTIR microscopy enable to look into the fate and effects of tattoo pigments in human skin
Authors: Schreiver Ines , Hesse Bernhard , Seim Christian , Castillo-Michel Hiram , Villanova Julie , Laux Peter , Dreiack Nadine , Penning Randolf , Tucoulou Remi , Cotte Marine , Luch Andreas
Published: September 2017

The increasing prevalence of tattoos provoked safety concerns with respect to particle distribution and effects inside the human body. We used skin and lymphatic tissues from human corpses to address local biokinetics by means of synchrotron X-ray fluorescence (XRF) techniques at both the micro (μ) and nano (ν) scale. Additional advanced mass spectrometry-based methodology enabled to demonstrate simultaneous transport of organic pigments, heavy metals and titanium dioxide from skin to regional lymph nodes. Among these compounds, organic pigments displayed the broadest size range with smallest species preferentially reaching the lymph nodes. Using synchrotron μ-FTIR analysis we were also able to detect ultrastructural changes of the tissue adjacent to tattoo particles through altered amide I α-helix to β-sheet protein ratios and elevated lipid contents. Altogether we report strong evidence for both migration and long-term deposition of toxic elements and tattoo pigments as well as for conformational alterations of biomolecules that likely contribute to cutaneous inflammation and other adversities upon tattooing.
Measuring Spectral Inconsistency of Multispectral Images for Detection and Segmentation of Retinal Degenerative Changes
Authors: Lian Jian , Zheng Yuanjie , Duan Peiyong , Jiao Wanzhen , Zhao Bojun , Ren Yanju , Shen Dinggang
Published: September 2017

Multispectral imaging (MSI) creates a series of en-face fundus spectral sections by leveraging an extensive range of discrete monochromatic light sources and allows for an examination of the retina’s early morphologic changes that are not generally visible with traditional fundus imaging modalities. An Ophthalmologist’s interpretation of MSI images is commonly conducted by qualitatively analyzing the spectral consistency between degenerated areas and normal ones, which characterizes the image variation across different spectra. Unfortunately, an ophthalmologist’s interpretation is practically difficult considering the fact that human perception is limited to the RGB color space, while an MSI sequence contains typically more than ten spectra. In this paper, we propose a method for measuring the spectral inconsistency of MSI images without supervision, which yields quantitative information indicating the pathological property of the tissue. Specifically, we define mathematically the spectral consistency as an existence of a pixel-specific latent feature vector and a spectrum-specific projection matrix, which can be used to reconstruct the representative features of pixels. The spectral inconsistency is then measured using the number of latent feature vectors required to reconstruct the representative features in practice. Experimental results from 54 MSI sequences show that our spectral inconsistency measurement is potentially invaluable for MSI-based ocular disease diagnosis.
Optical source of individual pairs of colour-conjugated photons
Authors: Sherkunov Yury , Whittaker David M. , Fal’ko Vladimir I.
Published: September 2017

We theoretically demonstrate that Kerr nonlinearity in optical circuits can lead to both resonant four-wave mixing and photon blockade, which can be used for high-yield generation of high-fidelity individual photon pairs with conjugated frequencies. We propose an optical circuit, which, in the optimal pulsed-drive regime, would produce photon pairs at the rate up to 5 × 105 
s−1 (0.5 pairs per pulse) with $${{\boldsymbol{g}}}^{{\bf{(2)}}}{\bf{(0)}}{\boldsymbol{ < }}{{\bf{10}}}^{-{\bf{2}}}$$

g

(2)

(0)
<

10

−
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for one of the conjugated frequencies. We show that such a scheme can be utilised to generate colour-entangled photons.
FGFR inhibitor, AZD4547, impedes the stemness of mammary epithelial cells in the premalignant tissues of MMTV-ErbB2 transgenic mice
Authors: Zhao Qingxia , Parris Amanda B. , Howard Erin W. , Zhao Ming , Ma Zhikun , Guo Zhiying , Xing Ying , Yang Xiaohe
Published: September 2017

The fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases (RTKs) regulates signaling pathways involved in cell proliferation and differentiation. Currently, the anti-tumor properties of FGFR inhibitors are being tested in preclinical and clinical studies. Nevertheless, reports on FGFR inhibitor-mediated breast cancer prevention are sparse. In this study, we investigated the anti-cancer benefits of AZD4547, an FGFR1-3 inhibitor, in ErbB2-overexpressing breast cancer models. AZD4547 (1–5 µM) demonstrated potent anti-proliferative effects, inhibition of stemness, and suppression of FGFR/RTK signaling in ErbB2-overexpressing human breast cancer cells. To study the in vivo effects of AZD4547 on mammary development, mammary epithelial cell (MEC) populations, and oncogenic signaling, MMTV-ErbB2 transgenic mice were administered AZD4547 (2–6 mg/kg/day) for 10 weeks during the ‘risk window’ for mammary tumor development. AZD4547 significantly inhibited ductal branching and MEC proliferation in vivo, which corroborated the in vitro anti-proliferative properties. AZD4547 also depleted CD24/CD49f-sorted MEC populations, as well as the CD61highCD49fhigh tumor-initiating cell-enriched population. Importantly, AZD4547 impaired stem cell-like characteristics in primary MECs and spontaneous tumor cells. Moreover, AZD4547 downregulated RTK, mTOR, and Wnt/β-catenin signaling pathways in premalignant mammary tissues. Collectively, our data provide critical preclinical evidence for AZD4547 as a potential breast cancer preventative and therapeutic agent.
Social resource foraging is guided by the principles of the Marginal Value Theorem
Authors: Turrin Courtney , Fagan Nicholas A. , Dal Monte Olga , Chang Steve W. C.
Published: September 2017

Optimality principles guide how animals adapt to changing environments. During foraging for nonsocial resources such as food and water, species across taxa obey a strategy that maximizes resource harvest rate. However, it remains unknown whether foraging for social resources also obeys such a strategic principle. We investigated how primates forage for social information conveyed by conspecific facial expressions using the framework of optimal foraging theory. We found that the canonical principle of Marginal Value Theorem (MVT) also applies to social resources. Consistent with MVT, rhesus macaques (Macaca mulatta) spent more time foraging for social information when alternative sources of information were farther away compared to when they were closer by. A comparison of four models of patch-leaving behavior confirmed that the MVT framework provided the best fit to the observed foraging behavior. This analysis further demonstrated that patch-leaving decisions were not driven simply by the declining value of the images in the patch, but instead were dependent upon both the instantaneous social value intake rate and current time in the patch.
A multiplex preclinical model for adenoid cystic carcinoma of the salivary gland identifies regorafenib as a potential therapeutic drug
Authors: Chen Chen , Choudhury Sujata , Wangsa Darawalee , Lescott Chamille J. , Wilkins Devan J. , Sripadhan Praathibha , Liu Xuefeng , Wangsa Danny , Ried Thomas , Moskaluk Christopher , Wick Michael J. , Glasgow Eric , Schlegel Richard , Agarwal Seema
Published: September 2017

Adenoid cystic carcinomas (ACC) are rare salivary gland cancers with a high incidence of metastases. In order to study this tumor type, a reliable model system exhibiting the molecular features of this tumor is critical, but none exists, thereby inhibiting in-vitro studies and the analysis of metastatic behavior. To address this deficiency, we have coupled an efficient method to establish tumor cell cultures, conditional reprogramming (CR), with a rapid, reproducible and robust in-vivo zebrafish model. We have established cell cultures from two individual ACC PDX tumors that maintain the characteristic MYB translocation. Additional mutations found in one ACC culture also seen in the PDX tumor. Finally, the CR/zebrafish model mirrors the PDX mouse model and identifies regorafenib as a potential therapeutic drug to treat this cancer type that mimic the drug sensitivity profile in PDX model, further confirming the unique advantages of multiplex system.
Alterations of Brain Functional Architecture Associated with Psychopathic Traits in Male Adolescents with Conduct Disorder
Authors: Pu Weidan , Luo Qiang , Jiang Yali , Gao Yidian , Ming Qingsen , Yao Shuqiao
Published: September 2017

Psychopathic traits of conduct disorder (CD) have a core callous-unemotional (CU) component and an impulsive-antisocial component. Previous task-driven fMRI studies have suggested that psychopathic traits are associated with dysfunction of several brain areas involved in different cognitive functions (e.g., empathy, reward, and response inhibition etc.), but the relationship between psychopathic traits and intrinsic brain functional architecture has not yet been explored in CD. Using a holistic brain-wide functional connectivity analysis, this study delineated the alterations in brain functional networks in patients with conduct disorder. Compared with matched healthy controls, we found decreased anti-synchronization between the fronto-parietal network (FPN) and default mode network (DMN), and increased intra-network synchronization within the frontothalamic–basal ganglia, right frontoparietal, and temporal/limbic/visual networks in CD patients. Correlation analysis showed that the weakened FPN-DMN interaction was associated with CU traits, while the heightened intra-network functional connectivity was related to impulsivity traits in CD patients. Our findings suggest that decoupling of cognitive control (FPN) with social understanding of others (DMN) is associated with the CU traits, and hyper-functions of the reward and motor inhibition systems elevate impulsiveness in CD.
Normothermic Microwave Irradiation Induces Death of HL-60 Cells through Heat-Independent Apoptosis
Authors: Asano Mamiko , Tanaka Satoshi , Sakaguchi Minoru , Matsumura Hitoshi , Yamaguchi Takako , Fujita Yoshikazu , Tabuse Katsuyoshi
Published: September 2017

Microwaves have been used in various cancer therapies to generate heat and increase tumor cell temperature; however, their use is limited by their side-effects in normal cells and the acquisition of heat resistance. We previously developed a microwave irradiation method that kills cultured cancer cells, including a human promyelomonocytic leukemia (HL-60) cell line, by maintaining a cellular temperature of 37 °C during treatment. In the present study, we investigated the mechanisms underlying HL-60 cell death during this treatment. The microwave-irradiated HL-60 cells appear to undergo caspase-independent apoptosis, whereby DNA fragmentation was induced by mitochondrial dysfunction-related expression of apoptosis-inducing factor (AIF). Caspase-dependent apoptosis was also interrupted by the loss of apoptotic protease-activating factor 1 (Apaf-1) and caspase 9. Moreover, these cells did not exhibit a heat-stress response, as shown by the lack of heat shock protein 70 (HSP70) upregulation. Alternatively, in HL-60 cells heated at 42.5 °C, HSP70 expression was upregulated and a pathway resembling death receptor-induced apoptosis was activated while mitochondrial function was maintained. Collectively, these results suggest that the cell death pathway activated by our 37 °C microwave irradiation method differs from that induced during other heating methods and support the use of normothermic microwave irradiation in clinical cancer treatments.
Selective tubular activation of hypoxia-inducible factor-2α has dual effects on renal fibrosis
Authors: Kong Kyoung Hye , Oh Hyung Jung , Lim Beom Jin , Kim Minsuk , Han Ki-Hwan , Choi Youn-Hee , Kwon Kihwan , Nam Bo Young , Park Kyoung Sook , Park Jung Tak , Han Seung Hyeok , Yoo Tae-Hyun , Lee Shina , Kim Seung-Jung , Kang Duk-Hee , Choi Kyu Bok , Eremina Vera , Quaggin Susan E. , Ryu Dong-Ryeol , Kang Shin-Wook
Published: September 2017

Hypoxia-inducible factor (HIF) is a key transcriptional factor in the response to hypoxia. Although the effect of HIF activation in chronic kidney disease (CKD) has been widely evaluated, the results have been inconsistent until now. This study aimed to investigate the effects of HIF-2α activation on renal fibrosis according to the activation timing in inducible tubule-specific transgenic mice with non-diabetic CKD. HIF-2α activation in renal tubular cells upregulated mRNA and protein expressions of fibronectin and type 1 collagen associated with the activation of p38 mitogen-activated protein kinase. In CKD mice, activation of HIF-2α at the beginning of CKD significantly aggravated renal fibrosis, whereas it did not lead to renal dysfunction. However, activation at a late-stage of CKD abrogated both renal dysfunction and fibrosis, which was associated with restoration of renal vasculature and amelioration of hypoxia through increased renal tubular expression of VEGF and its isoforms. As with tubular cells with HIF-2α activation, those under hypoxia also upregulated VEGF, fibronectin, and type 1 collagen expressions associated with HIF-1α activation. In conclusion, late-stage renal tubular HIF-2α activation has protective effects on renal fibrosis and the resultant renal dysfunction, thus it could represent a therapeutic target in late stage of CKD.
Functional neural changes associated with acquired amusia across different stages of recovery after stroke
Authors: Sihvonen Aleksi J. , Särkämö Teppo , Ripollés Pablo , Leo Vera , Saunavaara Jani , Parkkola Riitta , Rodríguez-Fornells Antoni , Soinila Seppo
Published: September 2017

Brain damage causing acquired amusia disrupts the functional music processing system, creating a unique opportunity to investigate the critical neural architectures of musical processing in the brain. In this longitudinal fMRI study of stroke patients (N = 41) with a 6-month follow-up, we used natural vocal music (sung with lyrics) and instrumental music stimuli to uncover brain activation and functional network connectivity changes associated with acquired amusia and its recovery. In the acute stage, amusic patients exhibited decreased activation in right superior temporal areas compared to non-amusic patients during instrumental music listening. During the follow-up, the activation deficits expanded to comprise a wide-spread bilateral frontal, temporal, and parietal network. The amusics showed less activation deficits to vocal music, suggesting preserved processing of singing in the amusic brain. Compared to non-recovered amusics, recovered amusics showed increased activation to instrumental music in bilateral frontoparietal areas at 3 months and in right middle and inferior frontal areas at 6 months. Amusia recovery was also associated with increased functional connectivity in right and left frontoparietal attention networks to instrumental music. Overall, our findings reveal the dynamic nature of deficient activation and connectivity patterns in acquired amusia and highlight the role of dorsal networks in amusia recovery.
Metabolic engineering for recombinant major ampullate spidroin 2 (MaSp2) synthesis in Escherichia coli
Authors: Cao Hao , Parveen Shafaq , Ding Ding , Xu Haijun , Tan Tianwei , Liu Luo
Published: September 2017

In this research, metabolic engineering was employed to synthesize the artificial major ampullate spidroin 2 (MaSp2) in the engineeredEscherichia coli. An iterative seamless splicing strategy was used to assemble the MaSp2 gene, which could reach 10000 base pairs, and more than 100 kDa protein was expected. However, only 55 kDa recombinant MaSp2 was obtained. Because MaSp2 is rich in alanine and glycine residues, Glycyl/alanyl-tRNA pool and extra amino acids adding were adopted in order to supplement alanine and glycine in the protein translation process. With the supplementary alanine and glycine (0.05 wt%) in the medium, MaSp2 constructed in pET28a(+) and Gly/Ala-tRNA constructed in pET22b(+) were co-expressed inEscherichia coliBL21 (DE3). As results, the artificial MaSp2 with 110 kDa molecular weight was obtained in the present work. This work demonstrates a successful example of applying metabolic engineering approaches and provided a potential way with the enhanced Glycyl/alanyl-tRNA pool to achieve the expression of high molecular weight protein with the repeated motifs in the engineeredEscherichia coli.
Reply to ‘Pitfalls of using confocal-microscopy based automated quantification of synaptic complexes in honeybee mushroom bodies (response
to Peng and Yang 2016)’
Authors: Peng Yi-Chan , Yang En-Cheng
Published: September 2017

In a comment on our Article “Sublethal Dosage of Imidacloprid Reduces the Microglomerular Density of Honey Bee Mushroom Bodies”, Rössler et al. assert that our reported counts are overall lower than previously reported due to the use of automated quantification. We address these issues in this reply.
Dogs are not better than humans at detecting coherent motion
Authors: Kanizsár Orsolya , Mongillo Paolo , Battaglini Luca , Campana Gianluca , Marinelli Lieta
Published: September 2017

The ability to perceive motion is one of the main properties of the visual system. Sensitivity in detecting coherent motion has been thoroughly investigated in humans, where thresholds for motion detection are well below 10% of coherence, i.e. of the proportion of dots coherently moving in the same direction, among a background of randomly moving dots. Equally low thresholds have been found in other species, including monkeys, cats and seals. Given the lack of data from the domestic dog, we tested 5 adult dogs on a conditioned discrimination task with random dot displays. In addition, five adult humans were tested in the same condition for comparative purposes. The mean threshold for motion detection in our dogs was 42% of coherence, while that of humans was as low as 5%. Therefore, dogs have a much higher threshold of coherent motion detection than humans, and possibly also than phylogenetically closer species that have been tested in similar experimental conditions. Various factors, including the relative role of global and local motion processing and experience with the experimental stimuli may have contributed to this result. Overall, this finding questions the general claim on dogs’ high performance in detecting motion.
A Class II small heat shock protein OsHsp18.0 plays positive roles in both biotic and abiotic defense responses in rice
Authors: Kuang Jie , Liu Jianzhong , Mei Jun , Wang Changchun , Hu Haitao , Zhang Yanjun , Sun Meihao , Ning Xi , Xiao Langtao , Yang Ling
Published: September 2017

Bacterial blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most devastating diseases of rice. However, the molecular mechanism underpinning the Xoo resistance of rice is still not fully understood. Here, we report that a class II small heat shock protein gene, OsHsp18.0, whose expression was differentially induced between a resistant and a susceptible variety in response to Xoo infection, plays positive roles in both biotic and abiotic resistance. The molecular chaperone activity of OsHsp18.0 was confirmed by a bacterium-expressed glutathione S-transferase fusion protein. Overexpression of OsHsp18.0 in a susceptible rice variety significantly enhanced its resistance to multiple Xoo strains, whereas silencing of OsHsp18.0 in a resistant variety drastically increased its susceptibility. The enhanced Xoo resistance in OsHsp18.0-overexpressing lines was positively correlated with the sensitized salicylic acid-dependent defense responses. In addition to disease resistance, the OsHsp18.0 overexpressing and silencing lines exhibited enhanced and reduced tolerance, respectively, to heat and salt treatments. The subcellular localization study revealed that the green fluorescent protein-OsHsp18.0 was enriched on the nuclear envelope, suggesting a potential role of OsHsp18.0 in the nucleo-cytoplasmic trafficking. Together, our results reveal that the rice OsHsp18.0 is a positive regulator in both biotic and abiotic defense responses.
Function Coupling Mechanism of PhuS and HemO in Heme Degradation
Authors: Lee Michael J. Y. , Wang Ye , Jiang Yafei , Li Xichen , Ma Jianqiu , Tan Hongwei , Turner-Wood Keegan , Rahman Mona N. , Chen Guangju , Jia Zongchao
Published: September 2017

Most bacteria possess only one heme-degrading enzyme for obtaining iron, however few bacteria such as Pseudomonas aeruginosa express two, namely PhuS and HemO. While HemO is a well-known heme oxygenase, previously we discovered that PhuS also possesses heme degradation activity and generates verdoheme, an intermediate of heme breakdown. To understand the coexistence of these two enzymes, using the DFT calculation we reveal that PhuS effectively enhances heme degradation through its participation in heme hydroxylation, the rate limiting reaction. Heme is converted to verdoheme in this reaction and the energy barrier for PhuS is substantially lower than for HemO. Thus, HemO is mainly involved in the ring opening reaction which converts verdoheme to biliverdin and free iron. Our kinetics experiments show that, in the presence of both PhuS and HemO, complete degradation of heme to biliverdin is enhanced. We further show that PhuS is more active than HemO using heme as a substrate and generates more CO. Combined experimental and theoretical results directly identify function coupling of this two-enzyme system, resulting in more efficient heme breakdown and utilization.
Timing for Surgical Stabilization with K-wires after Open Fractures of Proximal and Middle Phalangeal Shaft
Authors: Gao Yanchun , Wang Qiyang , Zhu Hongyi , Xu Zhengyu
Published: September 2017

The optimal timing for surgical stabilization after open fractures of proximal and middle phalangeal shaft remained unclear. Total 147 patients with single open fracture in proximal or middle phalangeal shaft (arrived within 8 hours) who received K-wire fixation from June 2012 to June 2015 were included for analysis. The timing for surgical stabilization of fractures (immediate or delayed) was decided according to the surgeons’ preferences. The Michigan hand outcomes questionnaire (MHQ) scores, grip strength and total active motion (TAM) one year after the initial surgery were similar between the two groups. There was no significant difference in the incidence of tenosynovitis, bone nonunion. The overall infection rate in immediate fixation group was slightly but not significantly higher compared with the delayed fixation group (29.2% versus 20.7% P = 0.212). However, patients with both palmar and dorsal wounds who received immediate fixation had much higher infection rate compared with delayed fixation (52.6% versus 22.7%, P = 0.047). The immediate fixation could reduce costs and the period of hospitalization. Open fractures with both palmar and dorsal wounds should be treated with delayed fixation of K-wires otherwise stabilized immediately after injury.