bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toward point-of-care management of chronic respiratory conditions: Electrochemical sensing of nitrite content in exhaled breath condensate using reduced graphene oxide
Authors: Gholizadeh Azam , Voiry Damien , Weisel Clifford , Gow Andrew , Laumbach Robert , Kipen Howard , Chhowalla Manish , Javanmard Mehdi 
Published: May 2017

AbstractWe present a portable non-invasive approach for measuring indicators of inflammation and oxidative stress in the respiratory tract by quantifying a biomarker in exhaled breath condensate (EBC). We discuss the fabrication and characterization of a miniaturized electrochemical sensor for detecting nitrite content in EBC using reduced graphene oxide. The nitrite content in EBC has been demonstrated to be a promising biomarker of inflammation in the respiratory tract, particularly in asthma. We utilized the unique properties of reduced graphene oxide (rGO); specifically, the material is resilient to corrosion while exhibiting rapid electron transfer with electrolytes, thus allowing for highly sensitive electrochemical detection with minimal fouling. Our rGO sensor was housed in an electrochemical cell fabricated from polydimethyl siloxane (PDMS), which was necessary to analyze small EBC sample volumes. The sensor is capable of detecting nitrite at a low over-potential of 0.7 V with respect to an Ag/AgCl reference electrode. We characterized the performance of the sensors using standard nitrite/buffer solutions, nitrite spiked into EBC, and clinical EBC samples. The sensor demonstrated a sensitivity of 0.21 μA μM−1 cm−2 in the range of 20–100 μM and of 0.1 μA μM−1 cm−2 in the range of 100–1000 μM nitrite concentration and exhibited a low detection limit of 830 nM in the EBC matrix. To benchmark our platform, we tested our sensors using seven pre-characterized clinical EBC samples with concentrations ranging between 0.14 and 6.5 μM. This enzyme-free and label-free method of detecting biomarkers in EBC can pave the way for the development of portable breath analyzers for diagnosing and managing changes in respiratory inflammation and disease.
Notch-mediated conversion of activated T cells into stem cell memory-like T cells for adoptive immunotherapy
Authors: Kondo Taisuke , Morita Rimpei , Okuzono Yuumi , Nakatsukasa Hiroko , Sekiya Takashi , Chikuma Shunsuke , Shichita Takashi , Kanamori Mitsuhiro , Kubo Masato , Koga Keiko , Miyazaki Takahiro , Kassai Yoshiaki , Yoshimura Akihiko 
Published: May 2017

AbstractAdoptive T-cell immunotherapy is a promising approach to cancer therapy. Stem cell memory T (TSCM) cells have been proposed as a class of long-lived and highly proliferative memory T cells. CD8+ TSCM cells can be generated in vitro from naive CD8+ T cells via Wnt signalling; however, methods do not yet exist for inducing TSCM cells from activated or memory T cells. Here, we show a strategy for generating TSCM-like cells in vitro (iTSCM cells) from activated CD4+ and CD8+ T cells in mice and humans by coculturing with stromal cells that express a Notch ligand. iTSCM cells lose PD-1 and CTLA-4 expression, and produce a large number of tumour-specific effector cells after restimulation. This method could therefore be used to generate antigen-specific effector T cells for adoptive immunotherapy.
Controlling for the species-area effect supports constrained long-term Mesozoic terrestrial vertebrate diversification
Authors: Close Roger A. , Benson Roger B.J. , Upchurch Paul , Butler Richard J. 
Published: May 2017

AbstractVariation in the geographic spread of fossil localities strongly biases inferences about the evolution of biodiversity, due to the ubiquitous scaling of species richness with area. This obscures answers to key questions, such as how tetrapods attained their tremendous extant diversity. Here, we address this problem by applying sampling standardization methods to spatial regions of equal size, within a global Mesozoic-early Palaeogene data set of non-flying terrestrial tetrapods. We recover no significant increase in species richness between the Late Triassic and the Cretaceous/Palaeogene (K/Pg) boundary, strongly supporting bounded diversification in Mesozoic tetrapods. An abrupt tripling of richness in the earliest Palaeogene suggests that this diversity equilibrium was reset following the K/Pg extinction. Spatial heterogeneity in sampling is among the most important biases of fossil data, but has often been overlooked. Our results indicate that controlling for variance in geographic spread in the fossil record significantly impacts inferred patterns of diversity through time.
TWEAK mediates inflammation in experimental atopic dermatitis and psoriasis
Authors: Sidler Daniel , Wu Ping , Herro Rana , Claus Meike , Wolf Dennis , Kawakami Yuko , Kawakami Toshiaki , Burkly Linda , Croft Michael 
Published: May 2017

AbstractAtopic dermatitis (AD) and psoriasis are driven by alternate type 2 and type 17 immune responses, but some proteins might be critical to both diseases. Here we show that a deficiency of the TNF superfamily molecule TWEAK (TNFSF12) in mice results in defective maintenance of AD-specific T helper type 2 (Th2) and psoriasis-specific Th17 cells in the skin, and impaired expression of disease-characteristic chemokines and cytokines, such as CCL17 and TSLP in AD, and CCL20 and IL-19 in psoriasis. The TWEAK receptor, Fn14, is upregulated in keratinocytes and dermal fibroblasts, and TWEAK induces these cytokines and chemokines alone and in synergy with the signature T helper cytokines of either disease, IL-13 and IL-17. Furthermore, subcutaneous injection of recombinant TWEAK into naive mice induces cutaneous inflammation with histological and molecular signs of both diseases. TWEAK is therefore a critical contributor to skin inflammation and a possible therapeutic target in AD and psoriasis.
Single-molecule detection of dihydroazulene photo-thermal reaction using break junction technique
Authors: Huang Cancan , Jevric Martyn , Borges Anders , Olsen Stine T. , Hamill Joseph M. , Zheng Jue-Ting , Yang Yang , Rudnev Alexander , Baghernejad Masoud , Broekmann Peter , Petersen Anne Ugleholdt , Wandlowski Thomas , Mikkelsen Kurt V. , Solomon Gemma C. , Brøndsted Nielsen Mogens , Hong Wenjing 
Published: May 2017

AbstractCharge transport by tunnelling is one of the most ubiquitous elementary processes in nature. Small structural changes in a molecular junction can lead to significant difference in the single-molecule electronic properties, offering a tremendous opportunity to examine a reaction on the single-molecule scale by monitoring the conductance changes. Here, we explore the potential of the single-molecule break junction technique in the detection of photo-thermal reaction processes of a photochromic dihydroazulene/vinylheptafulvene system. Statistical analysis of the break junction experiments provides a quantitative approach for probing the reaction kinetics and reversibility, including the occurrence of isomerization during the reaction. The product ratios observed when switching the system in the junction does not follow those observed in solution studies (both experiment and theory), suggesting that the junction environment was perturbing the process significantly. This study opens the possibility of using nano-structured environments like molecular junctions to tailor product ratios in chemical reactions.
TRPV4 plays a role in breast cancer cell migration via Ca2+-dependent activation of AKT and downregulation of E-cadherin cell cortex protein
Authors: Lee W H , Choong L Y , Jin T H , Mon N N , Chong S , Liew C S , Putti T , Lu S Y , Harteneck C , Lim Y P 
Published: May 2017

AbstractTRPV4 belongs to the ‘Transient Receptor Potential’ (TRP) superfamily. It has been identified to profoundly affect a variety of physiological processes, including nociception, heat sensation and inflammation. Unlike other TRP superfamily channels, its role in cancers are unknown until recently when we reported TRPV4 to be required for cancer cell softness that may promote breast cancer cell extravasation and metastasis. Here, we elucidated the molecular mechanisms mediated by TRPV4 in the metastatic breast cancer cells. TRPV4-mediated signaling was demonstrated to involve Ca2+-dependent activation of AKT and downregulation of E-cadherin expression, which was abolished upon TRPV4 silencing. Functionally, TRPV4-enhanced breast caner cell transendothelial migration requires AKT activity while a combination of transcriptional and post-translational regulation contributed to the TRPV4-mediated E-cadherin downregulation. Finally, mass spectrometry analysis revealed that TRPV4 is required for the expression of a network of secreted proteins involved in extracellular matrix remodeling. In conclusion, TRPV4 may regulate breast cancer metastasis by regulating cell softness through the Ca2+-dependent AKT-E-cadherin signaling axis and regulation of the expression of extracellular proteins.
AKT is indispensable for coordinating Par-4/JNK cross talk in p21 downmodulation during ER stress
Authors: Rasool R U , Nayak D , Chakraborty S , Faheem M M , Rah B , Mahajan P , Gopinath V , Katoch A , Iqra Z , Yousuf S K , Mukherjee D , Kumar L D , Nargotra A , Goswami A 
Published: May 2017

AbstractThe double-edged role of p21 to command survival and apoptosis is emerging. The current investigation highlights ER stress-mediated JNK activation that plausibly triggers cell death by attenuating endogenous p21 level. Here, we demonstrated that ER stress activator 3-AWA diminishes the p21 levels in cancer cells by averting the senescent phenotype to commence G2/M arrest. In essence, the deceleration in p21 level occurs through ER stress/JNK/Caspase-3 axis via activation/induction of proapoptotic Par-4 and inhibition of AKT. The molecular dynamics studies identified important interactions, which may be responsible for the AKT inhibition and efficacy of 3-AWA towards AKT binding pocket. Interestingly, the p21 deceleration was rescued by incubating the cells with 3-AWA in the presence of an ER stress inhibitor, Salubrinal. Furthermore, we demonstrated that p21 expression decreases solitarily in Par-4+/+ MEFs; albeit, ER stress-induced JNK activation was observed in both Par-4+/+ and Par-4−/− MEFs. Par-4 knockdown or overexpression studies established that ectopic Par-4 along with ER stress are not sufficient to downregulate p21 in PC-3 cells but are adequate for DU-145 cells and that the ER stress inflicted activation of JNK, inhibition of AKT and Par-4 induction are all crucial to p21 downmodulation by 3-AWA. By using isogenic cell lines, such as HCT-116 p53+/+ and HCT-116 p53−/−, we found that deceleration in p21 expression due to ER stress is p53 independent. Moreover, in orthotopic carcinogen-induced rat colorectal carcinoma model, we found that 3-AWA inhibits colorectal tumor growth and formation of colorectal polyps at a tolerable dose, similar to the first-line drug for colorectal cancer-5-fluorouracil.
Chaos as an intermittently forced linear system
Authors: Brunton Steven L. , Brunton Bingni W. , Proctor Joshua L. , Kaiser Eurika , Kutz J. Nathan 
Published: May 2017

AbstractUnderstanding the interplay of order and disorder in chaos is a central challenge in modern quantitative science. Approximate linear representations of nonlinear dynamics have long been sought, driving considerable interest in Koopman theory. We present a universal, data-driven decomposition of chaos as an intermittently forced linear system. This work combines delay embedding and Koopman theory to decompose chaotic dynamics into a linear model in the leading delay coordinates with forcing by low-energy delay coordinates; this is called the Hankel alternative view of Koopman (HAVOK) analysis. This analysis is applied to the Lorenz system and real-world examples including Earth’s magnetic field reversal and measles outbreaks. In each case, forcing statistics are non-Gaussian, with long tails corresponding to rare intermittent forcing that precedes switching and bursting phenomena. The forcing activity demarcates coherent phase space regions where the dynamics are approximately linear from those that are strongly nonlinear.
Palliative care for Parkinson’s disease: suggestions from a council of patient and carepartners
Authors: Hall Kirk , Sumrall Malenna , Thelen Gil , Kluger Benzi M. ,   on behalf of the 2015 Parkinson’s Disease Foundation sponsored “Palliative Care and Parkinson’s Disease” Patient Advisory Council
Published: May 2017

AbstractIn 2015, the Parkinson’s Disease Foundation sponsored the first international meeting on Palliative Care and Parkinson’s disease and the Patient Centered Outcomes Research Institute funded the first comparative effectiveness trial of palliative care for Parkinson’s disease. A council of Parkinson’s disease patients and carepartners was engaged to assist with both projects. This council wrote the following manuscript as an opinion piece addressed to the clinical and research community on how palliative care could be applied to people living with Parkinson’s disease and their families. The council endorses palliative care as an approach to the care of Parkinson’s disease patients and their families that seeks to reduce suffering through spiritual, psychosocial, and medical support. This approach should start at the time of diagnosis, as this is a very challenging time for patients and carepartners; includes better emotional support, educational resources, and closer follow-up than is currently standard; and continue through end-of-life care and bereavement.
Microfluidic Isolation of Circulating Tumor Cell Clusters by Size and Asymmetry
Authors: Au Sam H. , Edd Jon , Stoddard Amy E. , Wong Keith H. K. , Fachin Fabio , Maheswaran Shyamala , Haber Daniel A. , Stott Shannon L. , Kapur Ravi , Toner Mehmet 
Published: May 2017

AbstractCirculating tumor cell clusters (CTC clusters) are potent initiators of metastasis and potentially useful clinical markers for patients with cancer. Although there are numerous devices developed to isolate individual circulating tumor cells from blood, these devices are ineffective at capturing CTC clusters, incapable of separating clusters from single cells and/or cause cluster damage or dissociation during processing. The only device currently able to specifically isolate CTC clusters from single CTCs and blood cells relies on the batch immobilization of clusters onto micropillars which necessitates long residence times and causes damage to clusters during release. Here, we present a two-stage continuous microfluidic chip that isolates and recovers viable CTC clusters from blood. This approach uses deterministic lateral displacement to sort clusters by capitalizing on two geometric properties: size and asymmetry. Cultured breast cancer CTC clusters containing between 2–100 + cells were recovered from whole blood using this integrated two-stage device with minimal cluster dissociation, 99% recovery of large clusters, cell viabilities over 87% and greater than five-log depletion of red blood cells. This continuous-flow cluster chip will enable further studies examining CTC clusters in research and clinical applications.
Multiple viral infections in Agaricus bisporus - Characterisation of 18 unique RNA viruses and 8 ORFans identified by deep sequencing
Authors: Deakin Gregory , Dobbs Edward , Bennett Julie M. , Jones Ian M. , Grogan Helen M. , Burton Kerry S. 
Published: May 2017

AbstractThirty unique non-host RNAs were sequenced in the cultivated fungus, Agaricus bisporus, comprising 18 viruses each encoding an RdRp domain with an additional 8 ORFans (non-host RNAs with no similarity to known sequences). Two viruses were multipartite with component RNAs showing correlative abundances and common 3′ motifs. The viruses, all positive sense single-stranded, were classified into diverse orders/families. Multiple infections of Agaricus may represent a diverse, dynamic and interactive viral ecosystem with sequence variability ranging over 2 orders of magnitude and evidence of recombination, horizontal gene transfer and variable fragment numbers. Large numbers of viral RNAs were detected in multiple Agaricus samples; up to 24 in samples symptomatic for disease and 8–17 in asymptomatic samples, suggesting adaptive strategies for co-existence. The viral composition of growing cultures was dynamic, with evidence of gains and losses depending on the environment and included new hypothetical viruses when compared with the current transcriptome and EST databases. As the non-cellular transmission of mycoviruses is rare, the founding infections may be ancient, preserved in wild Agaricus populations, which act as reservoirs for subsequent cell-to-cell infection when host populations are expanded massively through fungiculture.
Organoid-based epithelial to mesenchymal transition (OEMT) model: from an intestinal fibrosis perspective
Authors: Hahn Soojung , Nam Myeong-Ok , Noh Jung Hyun , Lee Dong Hyeon , Han Hyun Wook , Kim Duk Hwan , Hahm Ki Baik , Hong Sung Pyo , Yoo Jun-Hwan , Yoo Jongman 
Published: May 2017

AbstractThe current in vitro or in vivo intestinal fibrosis models have many limitations. Recent advancements in the isolation and culturing of organoids has led to development of various three-dimensional (3D) intestinal disease models with in vivo physiology. In this study, we generated an organoid-based epithelial to mesenchymal transition (OEMT) model, which could be used as a novel intestinal fibrosis model. Intestinal epithelial organoids (IEOs) were isolated and cultured from the small intestines of normal mice. IEOs were treated with transforming growth factor- β1 (TGF-β1) or Tumor necrosis factor-α (TNF-α) to evaluate their phenotypic change. Raw 264.7 cells (macrophage) stimulated with lipopolysaccharide were co-cultured with IEOs in growth media with or without TGF-β1. TGF-β1 alone slightly induced epithelial to mesenchymal transition (EMT) in the IEOs but mainly disrupted them. Macrophage released cytokines synergistically induced mesenchymal phenotypic changes in TGF-β1 stimulated intestinal organoids. TNF-α and TGF-β1 synergistically induced proliferation of mesenchymal cells as well as EMT in the IEOs. We generated a novel OEMT model based on our finding that TNF-α and TGF-β synergistically induce type 2 EMT in IEOs. This 3D EMT model with in vivo physiology could be used to study EMT associated intestinal fibrosis.
Up-regulation of long non-coding RNA XLOC_010235 regulates epithelial-to-mesenchymal transition to promote metastasis by associating with Snail1 in gastric cancer
Authors: Liu Yu-yi , Chen Ze-hong , Peng Jian-jun , Wu Jia-lin , Yuan Yu-jie , Zhai Er-tao , Cai Shi-rong , He Yu-long , Song Wu 
Published: May 2017

AbstractWe previously performed long non-coding RNA (lncRNA) expression microarray analyses to identify novel indicators for gastric cancer (GC) metastasis and prognosis in which we identified lncRNA XLOC_010235 (XLOC) as a candidate RNA. However, XLOC_010235 molecular mechanism of action remains unclear. Gain and loss of function approaches were used to investigate the biological role of XLOC in vitro. The effects of XLOC on cell viability were assessed by CCK-8 proliferation assays. Real-time PCR, western-blot and immunofluorescence were used to evaluate the mRNA and protein expression of Snail and multiple EMT related molecules. The positive XLOC/Snail1 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis. Ectopic expression of XLOC facilitate cell viability, migration and invasion, leading to the acceleration of metastasis, while depletion of XLOC expression hindered cell migration and invasion. Moreover, over-expression of XLOC was found to play a important role in epithelial-to-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression, in which transcriptional factor Snail1 was involved. These results advance our understanding of the role of lncRNA XLOC_010235 as a active regulator of EMT by associating with Snail1, which may help in the development of new therapeutics.
Cinnamon induces browning in subcutaneous adipocytes
Authors: Kwan Hiu Yee , Wu Jiahui , Su Tao , Chao Xiao-Juan , Liu Bin , Fu Xiuqiong , Chan Chi Leung , Lau Rebecca Hiu Ying , Tse Anfernee Kai Wing , Han Quan Bin , Fong Wang Fun , Yu Zhi-ling 
Published: May 2017

AbstractBrowning is the process of increasing the number of brite cells, which helps to increase energy expenditure and reduce obesity. Consumption of natural and non-toxic herbal extracts that possess the browning effect is an attractive anti-obesity strategy. In this study, we examined the browning effect of cinnamon extract. We found that cinnamon extract (CE) induced typical brown adipocyte multiocular phenotype in 3T3-L1 adipocytes. The treatment also increased brown adipocytes markers and reduced white adipocytes markers in the 3T3-L1 adipocytes. In ex vivo studies, we found that CE increased brown adipocytes markers in the subcutaneous adipocytes isolated from db/db mice and diet-induced obesity (DIO) mice. However, CE did not significantly affect UCP1 expression in the adipocytes isolated from perinephric adipose tissue and epididymal adipose tissue. β3-adernergic receptor (β3-AR) antagonist reduced the CE-enhanced UCP1 expression, suggesting an involvement of the β3-AR activity. Oral administration of CE significantly increased UCP1 expression in the subcutaneous adipose tissue in vivo and reduced the body weight of the DIO mice. Taken together, our data suggest that CE has a browning effect in subcutaneous adipocytes. Our study suggests a natural non-toxic herbal remedy to reduce obesity.
Therapeutic effects of matrine derivate MASM in mice with collagen-induced arthritis and on fibroblast-like synoviocytes
Authors: Zou Yuming , Li Quan , Liu Denghui , Li Jia , Cai Qing , Li Chao , Zhao Qingjie , Xu Weidong 
Published: May 2017

AbstractMASM is a matrine derivate that exhibits a number of pharmacological effects, including immunosuppressive activity and anti-inflammatory properties. In this study, the mechanisms underlying the therapeutic efficacy of MASM in the treatment of rheumatoid arthritis were investigated using DBA/1 mice with collagen-induced arthritis (CIA) and fibroblast-like synoviocytes derived from rheumatoid arthritis patients (RA-FLS). We demonstrated that MASM markedly attenuated the severity of arthritis in CIA mice. The therapeutic effects were associated with ameliorated joint swelling and reduced bone erosion and destruction. Furthermore, the administration of MASM suppressed the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). In vitro, MASM inhibited the expression of pro-inflammatory cytokines (TNF-α, IL-6, IL-8) and matrix metalloproteinases (MMP-1, MMP-3 and MMP-13) by inhibiting both the phosphorylation of MAPKs and the activation of NF-κB in IL-1β-stimulated RA-FLS. Additionally, MASM could induce apoptosis of RA-FLS via mitochondrial and Akt signaling pathways in human RA-FLS. These findings suggest that MASM could attenuate arthritis severity in CIA mice at least partially by blocking the phosphorylation of MAPKs and the activation of NF-κB and by inducing apoptosis in RA-FLS. MASM could be a potent therapeutic agent for the treatment of RA.