bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxycycline induces apoptosis via ER stress selectively to cells with a cancer stem cell-like properties: importance of stem cell plasticity
Authors: Matsumoto Takashi , Uchiumi Takeshi , Monji Keisuke , Yagi Mikako , Setoyama Daiki , Amamoto Rie , Matsushima Yuichi , Shiota Masaki , Eto Masatoshi , Kang Dongchon 
Published: November 2017

AbstractTumor heterogeneity can be traced back to a small subset of cancer stem cells (CSCs), which can be derived from a single stem cell and show chemoresistance. Recent studies showed that CSCs are sensitive to mitochondrial targeting antibiotics such as doxycycline. However, little is known about how cancer cells undergo sphere formation and how antibiotics inhibit CSC proliferation. Here we show that under sphere-forming assay conditions, prostate cancer cells acquired CSC-like properties: promoted mitochondrial respiratory chain activity, expression of characteristic CSC markers and resistance to anticancer agents. Furthermore, those CSC-like properties could reversibly change depending on the culture conditions, suggesting some kinds of CSCs have plasticity in tumor microenvironments. The sphere-forming cells (i.e. cancer stem-like cells) showed increased contact between mitochondria and mitochondrial associated-endoplasmic reticulum (ER) membranes (MAM). Mitochondrial targeting doxycycline induced activating transcription factor 4 (ATF4) mediated expression of ER stress response and led to p53-upregulated modulator of apoptosis (PUMA)-dependent apoptosis only in the cancer stem-like cells. We also found that doxycycline effectively suppressed the sphere formation in vitro and blocked CD44v9-expressing tumor growth in vivo. In summary, these data provide new molecular findings that monolayer cancer cells acquire CSC-like properties in a reversible manner. These findings provide important insights into CSC biology and a potential new treatment of targeting mitochondria dependency.
HUWE1 variants cause dominant X-linked intellectual disability: a clinical study of 21 patients
Authors: Moortgat Stéphanie , Berland Siren , Aukrust Ingvild , Maystadt Isabelle , Baker Laura , Benoit Valerie , Caro-Llopis Alfonso , Cooper Nicola S. , Debray François-Guillaume , Faivre Laurence , Gardeitchik Thatjana , Haukanes Bjørn I. , Houge Gunnar , Kivuva Emma , Martinez Francisco , Mehta Sarju G. , Nassogne Marie-Cécile , Powell-Hamilton Nina , Pfundt Rolph , Rosello Monica , Prescott Trine , Vasudevan Pradeep , van Loon Barbara , Verellen-Dumoulin Christine , Verloes Alain , Lippe Charlotte von der , Wakeling Emma , Wilkie Andrew O. M. , Wilson Louise , Yuen Amy , Study DDD , Low Karen J. , Newbury-Ecob Ruth A. 
Published: November 2017

Abstract
Whole-gene duplications and missense variants in the HUWE1 gene (NM_031407.6) have been reported in association with intellectual disability (ID). Increased gene dosage has been observed in males with non-syndromic mild to moderate ID with speech delay. Missense variants reported previously appear to be associated with severe ID in males and mild or no ID in obligate carrier females. Here, we report the largest cohort of patients with HUWE1 variants, consisting of 14 females and 7 males, with 15 different missense variants and one splice site variant. Clinical assessment identified common clinical features consisting of moderate to profound ID, delayed or absent speech, short stature with small hands and feet and facial dysmorphism consisting of a broad nasal tip, deep set eyes, epicanthic folds, short palpebral fissures, and a short philtrum. We describe for the first time that females can be severely affected, despite preferential inactivation of the affected X chromosome. Three females with the c.329 G  >  A p.Arg110Gln variant, present with a phenotype of mild ID, specific facial features, scoliosis and craniosynostosis, as reported previously in a single patient. In these females, the X inactivation pattern appeared skewed in favour of the affected transcript. In summary, HUWE1 missense variants may cause syndromic ID in both males and females.
Opposite effects of Activin type 2 receptor ligands on cardiomyocyte proliferation during development and repair
Authors: Dogra Deepika , Ahuja Suchit , Kim Hyun-Taek , Rasouli S. Javad , Stainier Didier Y. R. , Reischauer Sven 
Published: November 2017

AbstractZebrafish regenerate damaged myocardial tissue very effectively. Hence, insights into the molecular networks underlying zebrafish heart regeneration might help develop alternative strategies to restore human cardiac performance. While TGF-β signaling has been implicated in zebrafish cardiac regeneration, the role of its individual ligands remains unclear. Here, we report the opposing expression response during zebrafish heart regeneration of two genes, mstnb and inhbaa, which encode TGF-β family ligands. Using gain-of-function (GOF) and loss-of-function (LOF) approaches, we show that these ligands mediate inverse effects on cardiac regeneration and specifically on cardiomyocyte (CM) proliferation. Notably, we find that Inhbaa functions as a CM mitogen and that its overexpression leads to accelerated cardiac recovery and scar clearance after injury. In contrast, mstnb GOF and inhbaa LOF both lead to unresolved scarring after cardiac injury. We further show that Mstnb and Inhbaa inversely control Smad2 and Smad3 transcription factor activities through alternate Activin type 2 receptors.
Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading
Authors: Goldstein Ido , Paakinaho Ville , Baek Songjoon , Sung Myong-Hee , Hager Gordon L. 
Published: November 2017

AbstractThe cytokines interleukin 1β and 6 (IL-1β, IL-6) mediate the acute phase response (APR). In liver, they regulate the secretion of acute phase proteins. Using RNA-seq in primary hepatocytes, we show that these cytokines regulate transcription in a bifurcated manner, leading to both synergistic and antagonistic gene expression. By mapping changes in enhancer landscape and transcription factor occupancy (using ChIP-seq), we show that synergistic gene induction is achieved by assisted loading of STAT3 on chromatin by NF-κB. With IL-6 treatment alone, STAT3 does not efficiently bind 20% of its coordinated binding sites. In the presence of IL-1β, NF-κB is activated, binds a subset of enhancers and primes their activity, as evidenced by increasing H3K27ac. This facilitates STAT3 binding and synergistic gene expression. Our findings reveal an enhancer-specific crosstalk whereby NF-κB enables STAT3 binding at some enhancers while perturbing it at others. This model reconciles seemingly contradictory reports of NF-κB-STAT3 crosstalk.
Chiral transport along magnetic domain walls in the quantum anomalous Hall effect
Authors: Rosen Ilan T. , Fox Eli J. , Kou Xufeng , Pan Lei , Wang Kang L. , Goldhaber-Gordon David 
Published: November 2017

AbstractThe quantum anomalous Hall effect in thin film magnetic topological insulators (MTIs) is characterized by chiral, one-dimensional conduction along the film edges when the sample is uniformly magnetized. This has been experimentally confirmed by measurements of quantized Hall resistance and near-vanishing longitudinal resistivity in magnetically doped (Bi,Sb)2Te3. Similar chiral conduction is expected along magnetic domain walls, but clear detection of these modes in MTIs has proven challenging. Here, we intentionally create a magnetic domain wall in an MTI, and study electrical transport along the domain wall. In agreement with theoretical predictions, we observe chiral transport along a domain wall. We present further evidence that two modes equilibrate while co-propagating along the length of the domain wall.
Hierarchically porous, and Cu- and Zn-containing γ-AlOOH mesostrands as adjuvants for cancer immunotherapy
Authors: Li Xia , Shenashen Mohamed A. , Wang Xiupeng , Ito Atsuo , Taniguchi Akiyoshi , EI-Safty Sherif A. 
Published: November 2017

AbstractAlum is the only licensed adjuvant by Food and Drug Administration of USA used in many human vaccines and has excellent safety record in clinical applications. However, alum hardly induces T helper 1 (Th1) immune responses that are required for anti-tumor immunity. In the present study, we fabricated hierarchical copper- and zinc- buds dressing γ-AlOOH mesostrands (Cu- and Zn-AMSs) with randomly wrinkled morphology, mesoscale void- or cave-like pockets, high-exposed surface coverage sites, and positive charge streams in saline. We confirmed that Cu- and Zn-AMSs promoted intracellular uptake of model cancer antigen (ovalbumin, OVA) by THP-1-differentiated macrophage-like cellsin vitro. Moreover, Cu- and Zn-AMSs enhanced maturation and cytokine release of bone marrow dendritic cellsin vitro.In vivostudy demonstrated that Cu- and Zn-AMSs markedly induced anti-tumor-immunity and enhanced CD4+and CD8+T cell populations in splenocytes of mice. These findings demonstrated that hierarchical copper- and zinc- buds dressing γ-AlOOH mesostrands, which are oriented in randomly wrinkled matrice, are suitable platforms as novel adjuvants for cancer immunotherapy.
Tabby graphene: Dimensional magnetic crossover in fluorinated graphite
Authors: Makarova T. L. , Shelankov A. L. , Shames A. I. , Zyrianova A. A. , Komlev A. A. , Chekhova G. N. , Pinakov D. V. , Bulusheva L. G. , Okotrub A. V. , Lähderanta E. 
Published: November 2017

AbstractTabby is a pattern of short irregular stripes, usually related to domestic cats. We have produced Tabby patterns on graphene by attaching fluorine atoms running as monoatomic chains in crystallographic directions. Separated by non-fluorinated sp2 carbon ribbons, sp3-hybridized carbon atoms bonded to zigzag fluorine chains produce sp2-sp3 interfaces and spin-polarized edge states localized on both sides of the chains. We have compared two kinds of fluorinated graphite samples C2F
x
, with x near to 1 and x substantially below 1. The magnetic susceptibility of C2F
x
(x < 1) shows a broad maximum and a thermally activated spin gap behaviour that can be understood in a two-leg spin ladder model with ferromagnetic legs and antiferromagnetic rungs; the spin gap constitutes about 450 K. Besides, stable room-temperature ferromagnetism is observed in C2F
x
(x < 1) samples: the crossover to a three-dimensional magnetic behaviour is due to the onset of interlayer interactions. Similarly prepared C2F
x
(x ≈ 1) samples demonstrate features of two-dimensional magnetism without signs of high-temperature magnetic ordering, but with transition to a superparamagnetic state below 40 K instead. The magnetism of the Tabby graphene is stable until 520 K, which is the temperature of the structural reconstruction of fluorinated graphite.
DHHC5-mediated palmitoylation of S1P receptor subtype 1 determines G-protein coupling
Authors: Badawy Shaymaa Mohamed Mohamed , Okada Taro , Kajimoto Taketoshi , Ijuin Takeshi , Nakamura Shun-ichi 
Published: November 2017

AbstractSphingosine 1-phosphate (S1P) is a pleiotropic lipid mediator involved in the regulation of immune cell trafficking and vascular permeability acting mainly through G-protein-coupled S1P receptors (S1PRs). However, mechanism underlying how S1PRs are coupled with G-proteins remains unknown. Here we have uncovered that palmitoylation of a prototypical subtype S1P1R is prerequisite for subsequent inhibitory G-protein (Gi) coupling. We have identified DHHC5 as an enzyme for palmitoylation of S1P1R. Under basal conditions, S1P1R was functionally associated with DHHC5 in the plasma membranes (PM) and was fully palmitoylated, enabling Gi coupling. Upon stimulation, the receptor underwent internalisation leaving DHHC5 in PM, resulting in depalmitoylation of S1P1R. We also revealed that while physiological agonist S1P-induced endocytosed S1P1R readily recycled back to PM, pharmacological FTY720-P-induced endocytosed S1P1R-positive vesicles became associated with DHHC5 in the later phase, persistently transmitting Gi signals there. This indicates that FTY720-P switches off the S1P signal in PM, while switching on its signal continuously inside the cells. We propose that DHHC5-mediated palmitoylation of S1P1R determines Gi coupling and its signalling in a spatio/temporal manner.
Evolving autonomous learning in cognitive networks
Authors: Sheneman Leigh , Hintze Arend 
Published: November 2017

AbstractThere are two common approaches for optimizing the performance of a machine: genetic algorithms and machine learning. A genetic algorithm is applied over many generations whereas machine learning works by applying feedback until the system meets a performance threshold. These methods have been previously combined, particularly in artificial neural networks using an external objective feedback mechanism. We adapt this approach to Markov Brains, which are evolvable networks of probabilistic and deterministic logic gates. Prior to this work MB could only adapt from one generation to the other, so we introduce feedback gates which augment their ability to learn during their lifetime. We show that Markov Brains can incorporate these feedback gates in such a way that they do not rely on an external objective feedback signal, but instead can generate internal feedback that is then used to learn. This results in a more biologically accurate model of the evolution of learning, which will enable us to study the interplay between evolution and learning and could be another step towards autonomously learning machines.
Risk of mortality during and after the 2011 Great East Japan Earthquake and Tsunami among older coastal residents
Authors: Aida Jun , Hikichi Hiroyuki , Matsuyama Yusuke , Sato Yukihiro , Tsuboya Toru , Tabuchi Takahiro , Koyama Shihoko , Subramanian S. V. , Kondo Katsunori , Osaka Ken , Kawachi Ichiro 
Published: November 2017

AbstractThe Japan Gerontological Evaluation Study is a nationwide cohort study of individuals aged 65 years and older established in July 2010. Seven months later, one of the study field sites was directly in the line of the 2011 Great East Japan Earthquake and Tsunami. Despite the 1-hour warning interval between the earthquake and tsunami, many coastal residents lost their lives. We analyzed the risk of all-cause mortality on the day of the disaster as well as in the 38-month interval after the disaster. Among 860 participants, 33 (3.8%) died directly because of the tsunami and an additional 95 people died during the 38-month follow-up period. Individuals with depressive symptoms had elevated risk of mortality on the day of the disaster (odds ratio = 3.90 [95% CI: 1.13, 13.47]). More socially connected people also suffered increased risk of mortality, although these estimates were not statistically significant. In contrast, after the disaster, frequent social interactions reverted back to predicting improved survival (hazard ratio = 0.46 (95% CI: 0.26, 0.82)). Depressive symptoms and stronger social connectedness were associated with increased risk of mortality on the day of the disaster. After the disaster, social interactions were linked to improved survival.
Estrogen receptor 1 (ESR1) regulates VEGFA in adipose tissue
Authors: Fatima L. A. , Campello R. S. , Santos R. de Souza , Freitas H. S. , Frank A. P , Machado U. F. , Clegg D. J. 
Published: November 2017

AbstractVascular endothelial growth factor A (VEGFA) is a key factor in the regulation of angiogenesis in adipose tissue. Poor vascularization during adipose tissue proliferation causes fibrosis and local inflammation, and is associated with insulin resistance. It is known that 17-beta estradiol (E2) regulates adipose tissue function and VEGFA expression in other tissues; however, the ability of E2 to regulate VEGFA in adipose tissue is currently unknown. In this study, we showed that, in 3T3-L1 cells, E2 and the estrogen receptor 1 (ESR1) agonist PPT induced VEGFA expression, while ESR1 antagonist (MPP), and selective knockdown of ESR1 using siRNA decreased VEGFA and prevented the ability of E2 to modulate its expression. Additionally, we found that E2 and PPT induced the binding of hypoxia inducible factor 1 alpha subunit (HIF1A) in the VEGFA gene promoter. We further found that VEGFA expression was lower in inguinal and gonadal white adipose tissues of ESR1 total body knockout female mice compared to wild type mice. In conclusion, our data provide evidence of an important role for E2/ESR1 in modulating adipose tissue VEGFA, which is potentially important to enhance angiogenesis, reduce inflammation and improve adipose tissue function.
Consistency and flexibility in solving spatial tasks: different horses show different cognitive styles
Authors: Baragli Paolo , Vitale Valentina , Sighieri Claudio , Lanata Antonio , Palagi Elisabetta , Reddon Adam R. 
Published: November 2017

AbstractIndividual animals vary in their behaviour and reactions to novel situations. These differences may extend to differences in cognition among individuals. We tested twenty-six horses for their ability to detour around symmetric and asymmetric obstacles. All of the animals were able to get around the barrier to reach a food target, but varied in their approach. Some horses moved slowly but were more accurate in choosing the shortest way. Other horses acted quickly, consistently detoured in the same direction, and did not reliably choose the shortest way. The remaining horses shifted from a faster, directionally consistent response with the symmetric barrier, to a slower but more accurate response with the asymmetric barrier. The asymmetric barrier induced a reduction in heart rate variability, suggesting that this is a more demanding task. The different approaches used to solve the asymmetric task may reflect distinct cognitive styles in horses, which vary among individuals, and could be linked to different personality traits. Understanding equine behaviour and cognition can inform horse welfare and management.
Identification of Borrelia protein candidates in mouse skin for potential diagnosis of disseminated Lyme borreliosis
Authors: Grillon Antoine , Westermann Benoît , Cantero Paola , Jaulhac Benoît , Voordouw Maarten J. , Kapps Delphine , Collin Elody , Barthel Cathy , Ehret-Sabatier Laurence , Boulanger Nathalie 
Published: November 2017

AbstractIn vector-borne diseases, the skin plays an essential role in the transmission of vector-borne pathogens between the vertebrate host and blood-feeding arthropods and in pathogen persistence.Borrelia burgdorferisensu lato is a tick-borne bacterium that causes Lyme borreliosis (LB) in humans. This pathogen may establish a long-lasting infection in its natural vertebrate host where it can persist in the skin and some other organs. Using a mouse model, we demonstrate thatBorreliatargets the skin regardless of the route of inoculation, and can persist there at low densities that are difficult to detect via qPCR, but that were infective for blood-feeding ticks. Application of immunosuppressive dermocorticoids at 40 days post-infection (PI) significantly enhanced theBorreliapopulation size in the mouse skin. We used non-targeted (Ge-LC-MS/MS) and targeted (SRM-MS) proteomics to detect severalBorrelia-specific proteins in the mouse skin at 40 days PI. DetectedBorreliaproteins included flagellin, VlsE and GAPDH. An important problem in LB is the lack of diagnosis methods capable of detecting active infection in humans suffering from disseminated LB. The identification ofBorreliaproteins in skin biopsies may provide new approaches for assessing active infection in disseminated manifestations.
Immune and Imaging Correlates of Mild Cognitive Impairment Conversion to Alzheimer’s Disease
Authors: La Rosa Francesca , Saresella Marina , Baglio Francesca , Piancone Federica , Marventano Ivana , Calabrese Elena , Nemni Raffaello , Ripamonti Enrico , Cabinio Monia , Clerici Mario 
Published: November 2017

AbstractAmnestic mild cognitive impairment (aMCI) conversion to Alzheimer’s disease (AD) is seen in a sizable portion of aMCI patients; correlates predicting such conversion are poorly defined but neuroinflammation and the reactivation of chronic viral infections are suspected to play a role in this phenomenon. We analyzed these aspects in two homogeneous groups of aMCI who did or did not convert to AD over a 24-months period. Results showed that at baseline in those aMCI individuals who did not convert to AD: 1) Aβ1-42 stimulated production of the pro-inflammatory cytokines IL6 and IL1β by CD14+ cells was significantly reduced (p = 0.01), 2) CD14+/IL-33+ cells were increased (p = 0.0004); 3) MFI of TLR8 and TLR9 was significantly increased, and 4) better preserved hippocampus volumes were observed and correlated with IL33+/CD14+ cells. Notably, Aβ1-42 stimulated production of the antiviral cytokine IFN-λ was increased as well in non-AD converters, although with a borderline statistical significance (p = 0.05). Data herein indicating that proinflammatory cytokines are reduced, whereas IFN-λ production and TLR8 and 9 MFI are augmented in those aMCI in whom AD conversion is not observed suggest that the ability to mount stronger antiviral response within an antiiflammatory milieu associates with lack of AD conversion.
Hypersensitivity of BRCA2 deficient cells to rosemary extract explained by weak PARP inhibitory activity
Authors: Su Cathy , Gius Jeffrey P. , Van Steenberg Julia , Haskins Alexis H. , Heishima Kazuki , Omata Chisato , Iwayama Masahiro , Murakami Mami , Mori Takashi , Maruo Kohji , Kato Takamitsu A. 
Published: November 2017

AbstractRosemary extract is used in food additives and traditional medicine and has been observed to contain anti-tumor activity. In this study, rosemary extract is hypothesized to induce synthetic lethality in BRCA2 deficient cells by PARP inhibition. Chinese hamster lung V79 cells and its mutant cell lines, V-C8 (BRCA2 deficient) and V-C8 with BRCA2 gene correction were used. Rosemary extract and its major constituent chemicals were tested for their cytotoxicity by colony formation assay in cells of different BRCA2 status. The latter chemicals were tested for inhibitory effect of poly (ADP-ribose) polymerase (PARP) activity in vitro and in vivo. Rosemary has shown selective cytotoxicity against V-C8 cells (IC50 17 µg/ml) compared to V79 cells (IC50 26 µg/ml). Among tested chemicals, gallic acid and carnosic acid showed selective cytotoxicity to V-C8 cells along with PARP inhibitory effects. Carnosol showed comparative PARP inhibitory effects at 100 µM compared to carnosic acid and gallic acid, but the selective cytotoxicity was not observed. In conclusion, we predict that within rosemary extract two specific constituent components; gallic acid and carnosic acid were the cause for the synthetic lethality.