bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractT-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

AbstractRetinitis 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

AbstractAlternative 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

AbstractAlthough 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

AbstractMicrotus 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

AbstractPeat 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

AbstractSingle-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

AbstractThe 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

AbstractWe 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

AbstractThe 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

AbstractMultispectral 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

AbstractWe 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)
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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

AbstractThe 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

AbstractOptimality 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

AbstractAdenoid 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.