bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 3D-printed platform for modular neuromuscular motor units
Authors: Cvetkovic Caroline , Rich Max H. , Raman Ritu , Kong Hyunjoon , Bashir Rashid 
Published: June 2017

AbstractA complex and functional living cellular system requires the interaction of one or more cell types to perform specific tasks, such as sensing, processing, or force production. Modular and flexible platforms for fabrication of such multi-cellular modules and their characterization have been lacking. Here, we present a modular cellular system, made up of multi-layered tissue rings containing integrated skeletal muscle and motor neurons (MNs) embedded in an extracellular matrix. The MNs were differentiated from mouse embryonic stem cells through the formation of embryoid bodies (EBs), which are spherical aggregations of cells grown in a suspension culture. The EBs were integrated into a tissue ring with skeletal muscle, which was differentiated in parallel, to create a co-culture amenable to both cell types. The multi-layered rings were then sequentially placed on a stationary three-dimensional-printed hydrogel structure resembling an anatomical muscle–tendon–bone organization. We demonstrate that the site-specific innervation of a group of muscle fibers in the multi-layered tissue rings allows for muscle contraction via chemical stimulation of MNs with glutamate, a major excitatory neurotransmitter in the mammalian nervous system, with the frequency of contraction increasing with glutamate concentration. The addition of tubocurarine chloride (a nicotinic receptor antagonist) halted the contractions, indicating that muscle contraction was MN induced. With a bio-fabricated system permitting controllable mechanical and geometric attributes in a range of length scales, our novel engineered cellular system can be utilized for easier integration of other modular “building blocks” in living cellular and biological machines.
A novel humanized mouse lacking murine P450 oxidoreductase for studying human drug metabolism
Authors: Barzi Mercedes , Pankowicz Francis P. , Zorman Barry , Liu Xing , Legras Xavier , Yang Diane , Borowiak Malgorzata , Bissig-Choisat Beatrice , Sumazin Pavel , Li Feng , Bissig Karl-Dimiter 
Published: June 2017

AbstractOnly one out of 10 drugs in development passes clinical trials. Many fail because experimental animal models poorly predict human xenobiotic metabolism. Human liver chimeric mice are a step forward in this regard, as the human hepatocytes in chimeric livers generate human metabolites, but the remaining murine hepatocytes contain an expanded set of P450 cytochromes that form the major class of drug-metabolizing enzymes. We therefore generated a conditional knock-out of the NADPH-P450 oxidoreductase (Por) gene combined with Il2rg
− /−
/Rag2
− /−
/Fah
− /−
(PIRF) mice. Here we show that homozygous PIRF mouse livers are readily repopulated with human hepatocytes, and when the murine Por gene is deleted (<5%), they predominantly use human cytochrome metabolism. When given the anticancer drug gefitinib or the retroviral drug atazanavir, the Por-deleted humanized PIRF mice develop higher levels of the major human metabolites than current models. Humanized, murine Por-deficient PIRF mice can thus predict human drug metabolism and should be useful for preclinical drug development.
Improving Dialysis Adherence for High Risk Patients Using Automated Messaging: Proof of Concept
Authors: Som A. , Groenendyk J. , An T. , Patel K. , Peters R. , Polites G. , Ross W. R. 
Published: June 2017

AbstractComorbidities and socioeconomic barriers often limit patient adherence and self-management with hemodialysis. Missed sessions, often associated with communication barriers, can result in emergency dialysis and avoidable hospitalizations. This proof of concept study explored using a novel digital-messaging platform, EpxDialysis, to improve patient-to-dialysis center communication via widely available text messaging and telephone technology. A randomized controlled trial was conducted through Washington University-affiliated hemodialysis centers involving ESRD patients with poor attendance, defined as missing 2–6 sessions over the preceding 12 weeks. A cross-over study design evaluated appointment adherence between intervention and control groups. Comparing nonadherence rates eight weeks prior to enrollment, median appointment adherence after using the system increased by 75%, and median number of unintended hospitalization days fell by 31%. A conservative cost-benefit analysis of EpxDialysis demonstrates a 1:36 savings ratio from appointment adherence. EpxDialysis is a low-risk, cost-effective, intervention for increasing hemodialysis adherence in high-risk patients, especially at centers caring for vulnerable and low-income patients.
Sustained release from a metal - Analgesics entrapped within biocidal silver
Authors: Menagen Barak , Pedahzur Rami , Avnir David 
Published: June 2017

AbstractMatrices for sustained release of drugs have been based on polymers, biomaterials and oxides. The use of the major family of metals as matrices for sustained release is, to the best of our knowledge, unknown. In this context we describe a new family of bio-composites for sustained release of drugs, namely analgesic drugs entrapped within metallic silver. Synthetic methodologies were developed for the preparation of ibuprofen@Ag, naproxen@Ag, tramadol@Ag and bupivacaine@Ag composites. Detailed kinetic analysis of the release of the drugs from within the metal, is provided, demonstrating that metals can indeed serve as reservoirs for drug release. The metal in our case acts not only as a drug releasing source, but also as an antibacterial agent and this property of the composites was studied. Unexpectedly, it was found that the entrapment of the analgesics within silver, dramatically enhances the growth inhibition activity of wild typePseudomonas aeruginosa, exceeding by far the inhibition activity of the separate components. A mechanism for this interesting observation is provided. The strong antimicrobial activity combined with the analgesic activity open the road for future applications of these materials as dual-purpose components in wound treatment.
Versatility of nodal affiliation to communities
Authors: Shinn Maxwell , Romero-Garcia Rafael , Seidlitz Jakob , Váša František , Vértes Petra E. , Bullmore Edward 
Published: June 2017

AbstractGraph theoretical analysis of the community structure of networks attempts to identify the communities (or modules) to which each node affiliates. However, this is in most cases an ill-posed problem, as the affiliation of a node to a single community is often ambiguous. Previous solutions have attempted to identify all of the communities to which each node affiliates. Instead of taking this approach, we introduce versatility, V, as a novel metric of nodal affiliation: V ≈ 0 means that a node is consistently assigned to a specific community; V >> 0 means it is inconsistently assigned to different communities. Versatility works in conjunction with existing community detection algorithms, and it satisfies many theoretically desirable properties in idealised networks designed to maximise ambiguity of modular decomposition. The local minima of global mean versatility identified the resolution parameters of a hierarchical community detection algorithm that least ambiguously decomposed the community structure of a social (karate club) network and the mouse brain connectome. Our results suggest that nodal versatility is useful in quantifying the inherent ambiguity of modular decomposition.
Aldosterone Modulates the Association between NCC and ENaC
Authors: Wynne Brandi M. , Mistry Abinash C. , Al-Khalili Otor , Mallick Rickta , Theilig Franziska , Eaton Douglas C. , Hoover Robert S. 
Published: June 2017

AbstractDistal sodium transport is a final step in the regulation of blood pressure. As such, understanding how the two main sodium transport proteins, the thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC), are regulated is paramount. Both are expressed in the late distal nephron; however, no evidence has suggested that these two sodium transport proteins interact. Recently, we established that these two sodium transport proteins functionally interact in the second part of the distal nephron (DCT2). Given their co-localization within the DCT2, we hypothesized that NCC and ENaC interactions might be modulated by aldosterone (Aldo). Aldo treatment increased NCC and αENaC colocalization (electron microscopy) and interaction (coimmunoprecipitation). Finally, with co-expression of the Aldo-induced protein serum- and glucocorticoid-inducible kinase 1 (SGK1), NCC and αENaC interactions were increased. These data demonstrate that Aldo promotes increased interaction of NCC and ENaC, within the DCT2 revealing a novel method of regulation for distal sodium reabsorption.
Coordination of Bactericidal and Iron Regulatory Functions of Hepcidin in Innate Antimicrobial Immunity in a Zebrafish Model
Authors: Jiang Xiao-feng , Liu Zhi-fei , Lin Ai-fu , Xiang Li-xin , Shao Jian-zhong 
Published: June 2017

AbstractHepcidin acts as both an antimicrobial peptide and a hormonal regulator of iron homeostasis; however, the biological significance of this dual-function in immune reactions remains elusive. In this study, we provide experimental evidence regarding the coordination of this dual-function in the innate antimicrobial immunity using a zebrafish model. The transcription of hepcidin gene was significantly upregulated in liver by Aeromonas hydrophila (A.h) DNA stimulation, which was accompanied by an increase of hepcidin protein and a decrease of iron concentration in serum. Thus, an enhanced bactericidal activity against A.h and Escherichia coli and inhibitory effects on A.h growth and OmpA expression were observed in A.h cells, the latter of which made the bacterium more susceptible to complement attack. The enhanced bacteriostatic activities in serum following the stimulation were dramatically impaired by neutralizing hepcidin or restoring iron to the samples. Immuno-protection assay showed that zebrafish administrated with A.h DNA or designed CpG-ODNs had a significantly enhanced defence against A.h and Vibrio alginolyticus infections, which was also eliminated by the neutralization of hepcidin. Results indicate that the induction of hepcidin leads to the decrease of iron in circulation, which eventually limits iron availability to invading microorganisms, thus contributing to host defence.
Dacomitinib, a pan-inhibitor of ErbB receptors, suppresses growth and invasive capacity of chemoresistant ovarian carcinoma cells
Authors: Momeny Majid , Zarrinrad Ghazaleh , Moghaddaskho Farima , Poursheikhani Arash , Sankanian Ghazaleh , Zaghal Azam , Mirshahvaladi Shahab , Esmaeili Fatemeh , Eyvani Haniyeh , Barghi Farinaz , Sabourinejad Zahra , Alishahi Zivar , Yousefi Hassan , Ghasemi Reza , Dardaei Leila , Bashash Davood , Chahardouli Bahram , Dehpour Ahmad R. , Tavakkoly-Bazzaz Javad , Alimoghaddam Kamran , Ghavamzadeh Ardeshir , Ghaffari Seyed H. 
Published: June 2017

AbstractEpithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy worldwide. Development of chemoresistance and peritoneal dissemination of EOC cells are the major reasons for low survival rate. Targeting signal transduction pathways which promote therapy resistance and metastatic dissemination is the key to successful treatment. Members of the ErbB family of receptors are over-expressed in EOC and play key roles in chemoresistance and invasiveness. Despite this, single-targeted ErbB inhibitors have demonstrated limited activity in chemoresistant EOC. In this report, we show that dacomitinib, a pan-ErbB receptor inhibitor, diminished growth, clonogenic potential, anoikis resistance and induced apoptotic cell death in therapy-resistant EOC cells. Dacominitib inhibited PLK1-FOXM1 signalling pathway and its down-stream targets Aurora kinase B and survivin. Moreover, dacomitinib attenuated migration and invasion of the EOC cells and reduced expression of epithelial-to-mesenchymal transition (EMT) markers ZEB1, ZEB2 and CDH2 (which encodes N-cadherin). Conversely, the anti-tumour activity of single-targeted ErbB agents including cetuximab (a ligand-blocking anti-EGFR mAb), transtuzumab (anti-HER2 mAb), H3.105.5 (anti-HER3 mAb) and erlotinib (EGFR small-molecule tyrosine kinase inhibitor) were marginal. Our results provide a rationale for further investigation on the therapeutic potential of dacomitinib in treatment of the chemoresistant EOC.
A Gelatin-sulfonated Silk Composite Scaffold based on 3D Printing Technology Enhances Skin Regeneration by Stimulating Epidermal Growth and Dermal Neovascularization
Authors: Xiong Si , Zhang Xianzhu , Lu Ping , Wu Yan , Wang Quan , Sun Heng , Heng Boon Chin , Bunpetch Varitsara , Zhang Shufang , Ouyang Hongwei 
Published: June 2017

AbstractOne of the key problems hindering skin repair is the deficiency of dermal vascularization and difficulty of epidermis regeneration, which makes it challenging to fabricate scaffolds that can biologically fulfill the requirements for skin regeneration. To overcome this problem, three-dimensional printing was used to fabricate a gelatin-sulfonated silk composite scaffold that was incorporated with basic fibroblast growth factor 2 (FGF-2) through binding with a sulfonic acid group (SO3) (3DG-SF-SO3-FGF). The efficacy and mechanism by which the 3DG-SF-SO3-FGF scaffolds promote skin regeneration were investigated both within in vitro cell culture and in vivo with a full-thickness skin defect model. The histological results showed that the gelatin-sulfonated silk composite scaffolds promoted granulation, and that incorporation of FGF-2 significantly enhanced the regeneration of skin-like tissues after implantation in rat skin defects for 14 and 28 days. Further investigations demonstrated that 3DG-SF-SO3-FGF scaffolds might stimulate dermal vascularization. These findings thus suggest that incorporation of FGF-2 into the 3D printed scaffolds is a viable strategy for enhancing skin regeneration.
Global rainfall erosivity assessment based on high-temporal resolution rainfall records
Authors: Panagos Panos , Borrelli Pasquale , Meusburger Katrin , Yu Bofu , Klik Andreas , Jae Lim Kyoung , Yang Jae E. , Ni Jinren , Miao Chiyuan , Chattopadhyay Nabansu , Sadeghi Seyed Hamidreza , Hazbavi Zeinab , Zabihi Mohsen , Larionov Gennady A. , Krasnov Sergey F. , Gorobets Andrey V. , Levi Yoav , Erpul Gunay , Birkel Christian , Hoyos Natalia , Naipal Victoria , Oliveira Paulo Tarso S. , Bonilla Carlos A. , Meddi Mohamed , Nel Werner , Al Dashti Hassan , Boni Martino , Diodato Nazzareno , Van Oost Kristof , Nearing Mark , Ballabio Cristiano 
Published: June 2017

AbstractThe exposure of the Earth’s surface to the energetic input of rainfall is one of the key factors controlling water erosion. While water erosion is identified as the most serious cause of soil degradation globally, global patterns of rainfall erosivity remain poorly quantified and estimates have large uncertainties. This hampers the implementation of effective soil degradation mitigation and restoration strategies. Quantifying rainfall erosivity is challenging as it requires high temporal resolution(<30 min) and high fidelity rainfall recordings. We present the results of an extensive global data collection effort whereby we estimated rainfall erosivity for 3,625 stations covering 63 countries. This first ever Global Rainfall Erosivity Database was used to develop a global erosivity map at 30 arc-seconds(~1 km) based on a Gaussian Process Regression(GPR). Globally, the mean rainfall erosivity was estimated to be 2,190 MJ mm ha−1 h−1 yr−1, with the highest values in South America and the Caribbean countries, Central east Africa and South east Asia. The lowest values are mainly found in Canada, the Russian Federation, Northern Europe, Northern Africa and the Middle East. The tropical climate zone has the highest mean rainfall erosivity followed by the temperate whereas the lowest mean was estimated in the cold climate zone.
The role of SET/I2PP2A in canine mammary tumors
Authors: Kake Satoru , Tsuji Shunya , Enjoji Shuhei , Hanasaki Sayaka , Hayase Hiroshi , Yabe Ryotaro , Tanaka Yuiko , Nakagawa Takayuki , Liu Hao-Ping , Chang Shih-Chieh , Usui Tatsuya , Ohama Takashi , Sato Koichi 
Published: June 2017

AbstractCanine mammary tumor is the most common neoplasm in female dogs, and it has generated considerable attention as a translational model for human breast cancer. Ser/Thr protein phosphatase 2A (PP2A) plays a critical role as a tumor suppressor, and SET/I2PP2A, the endogenous inhibitory protein of PP2A, binds directly to PP2A and suppresses its phosphatase activity. Here, we investigated the role of SET in the tumorigenic growth in canine mammary tumor as well as in the sensitivity of tumors to existing therapeutics. Elevated protein levels of SET were observed in advanced-stage of canine mammary tumor tissues of dogs compared with paired normal tissues. Knockdown of SET expression in a canine mammary tumor cell line CIP-m led to increased PP2A activity and decreased cell proliferation, colony formation, and in vivo tumor growth. We observed suppression of mTOR, β-catenin, and NFκB signaling by SET knockdown. The sensitivity of CIP-m cells to doxorubicin was decreased by SET knockdown, while SET knockdown in CIP-m cells did not affect sensitivity to 4-OH-tamoxifen, carboplatin, bortezomib, and X-ray radiation. These data suggest that SET plays important roles in the tumor progression of a subset of canine mammary tumor by suppressing PP2A activity and enhancing mTOR, β-catenin, and NFκB signaling.
Experimental Demonstration of Four-Dimensional Photonic Spatial Entanglement between Multi-core Optical Fibres
Authors: Lee Hee Jung , Choi Sang-Kyung , Park Hee Su 
Published: June 2017

AbstractFibre transport of multi-dimensional photonic quantum states promises high information capacity per photon without space restriction. This work experimentally demonstrates transmission of spatial ququarts through multi-core optical fibres and measurement of the entanglement between two fibres with quantum state analyzers, each composed of a spatial light modulator and a single-mode fibre. Quantum state tomography reconstructs the four-dimension entangled state that verifies the nonlocality through concurrences in two-dimensional subspaces, a lower bound of four-dimensional concurrence and a Bell-type CGLMP inequality.
Effect of H2O Adsorption on Negative Differential Conductance Behavior of Single Junction
Authors: Li Zong-Liang , Yi Xiao-Hua , Liu Ran , Bi Jun-Jie , Fu Huan-Yan , Zhang Guang-Ping , Song Yu-Zhi , Wang Chuan-Kui 
Published: June 2017

AbstractLarge negative differential conductance (NDC) at lower bias regime is a very desirable functional property for single molecular device. Due to the non-conjugated segment separating two conjugated branches, the single thiolated arylethynylene molecule with 9,10-dihydroanthracene core (denoted as TADHA) presents excellent NDC behavior in lower bias regime. Based on the ab initio calculation and non-equilibrium Green’s function formalism, the NDC behavior of TADHA molecular device and the H2O-molecule-adsorption effects are studied systematically. The numerical results show that the NDC behavior of TADHA molecular junction originates from the Stark effect of the applied bias which splits the degeneration of the highest occupied molecular orbital (HOMO) and HOMO-1. The H2O molecule adsorbed on the terminal sulphur atom strongly suppresses the conductance of TADHA molecular device and destroys the NDC behavior in the lower bias regime. Single or separated H2O molecules adsorbed on the backbone of TADHA molecule can depress the energy levels of molecular orbitals, but have little effects on the NDC behavior of the TADHA molecular junction. Aggregate of several H2O molecules adsorbed on one branch of TADHA molecule can dramatically enhance the conductance and NDC behavior of the molecular junction, and result in rectifier behavior.
Identification of introns harboring functional sequence elements through positional conservation
Authors: Chorev Michal , Joseph Bekker Alan , Goldberger Jacob , Carmel Liran 
Published: June 2017

AbstractMany human introns carry out a function, in the sense that they are critical to maintain normal cellular activity. Their identification is fundamental to understanding cellular processes and disease. However, being noncoding elements, such functional introns are poorly predicted based on traditional approaches of sequence and structure conservation. Here, we generated a dataset of human functional introns that carry out different types of functions. We showed that functional introns share common characteristics, such as higher positional conservation along the coding sequence and reduced loss rates, regardless of their specific function. A unique property of the data is that if an intron is unknown to be functional, it still does not mean that it is indeed non-functional. We developed a probabilistic framework that explicitly accounts for this unique property, and predicts which specific human introns are functional. We show that we successfully predict function even when the algorithm is trained on introns with a different type of function. This ability has many implications in studying regulatory networks, gene regulation, the effect of mutations outside exons on human disease, and on our general understanding of intron evolution and their functional exaptation in mammals.
Regulation of Drosophila Lifespan by bellwether Promoter Alleles
Authors: Garcia Júlia Frankenberg , Carbone Mary Anna , Mackay Trudy F. C. , Anholt Robert R. H. 
Published: June 2017

AbstractLongevity varies among individuals, but how natural genetic variation contributes to variation in lifespan is poorly understood. Drosophila melanogaster presents an advantageous model system to explore the genetic underpinnings of longevity, since its generation time is brief and both the genetic background and rearing environment can be precisely controlled. The bellwether (blw) gene encodes the α subunit of mitochondrial ATP synthase. Since metabolic rate may influence lifespan, we investigated whether alternative haplotypes in the blw promoter affect lifespan when expressed in a co-isogenic background. We amplified 521 bp upstream promoter sequences containing alternative haplotypes and assessed promoter activity both in vitro and in vivo using a luciferase reporter system. The AG haplotype showed significantly greater expression of luciferase than the GT haplotype. We then overexpressed a blw cDNA construct driven by either the AG or GT haplotype promoter in transgenic flies and showed that the AG haplotype also results in greater blw cDNA expression and a significant decrease in lifespan relative to the GT promoter haplotype, in male flies only. Thus, our results show that naturally occurring regulatory variants of blw affect lifespan in a sex-specific manner.