bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRAIL-based gene delivery and therapeutic
strategies
Authors: Zhong Hui-hai , Wang Hui-yuan , Li Jian , Huang Yong-zhuo 
Published: August 2019

AbstractTRAIL (tumor necrosis factor-related apoptosis-inducing ligand), also
known as APO2L, belongs to the tumor necrosis factor family. By binding to the death
receptor 4 (DR4) or DR5, TRAIL induces apoptosis of tumor cells without causing side
toxicity in normal tissues. In recent years TRAIL-based therapy has attracted great
attention for its promise of serving as a cancer drug candidate. However, the
treatment efficacy of TRAIL protein was under expectation in the clinical trials
because of the short half-life and the resistance of cancer cells. TRAIL gene
transfection can produce a “bystander effect” of tumor cell killing and provide a
potential solution to TRAIL-based cancer therapy. In this review we focus on TRAIL
gene therapy and various design strategies of TRAIL DNA delivery including non-viral
vectors and cell-based TRAIL therapy. In order to sensitize the tumor cells to
TRAIL-induced apoptosis, combination therapy of TRAIL DNA with other drugs by the
codelivery methods for yielding a synergistic antitumor efficacy is summarized. The
opportunities and challenges of TRAIL-based gene delivery and therapy are
discussed.
Kinetic asymmetry allows macromolecular catalysts to drive an information ratchet
Authors: Astumian R. Dean 
Published: August 2019

AbstractMolecular machines carry out their function by equilibrium mechanical motions in environments that are far from thermodynamic equilibrium. The mechanically equilibrated character of the trajectories of the macromolecule has allowed development of a powerful theoretical description, reminiscent of Onsager’s trajectory thermodynamics, that is based on the principle of microscopic reversibility. Unlike the situation at thermodynamic equilibrium, kinetic parameters play a dominant role in determining steady-state concentrations away from thermodynamic equilibrium, and kinetic asymmetry provides a mechanism by which chemical free-energy released by catalysis can drive directed motion, molecular adaptation, and self-assembly. Several examples drawn from the recent literature, including a catenane-based chemically driven molecular rotor and a synthetic molecular assembler or pump, are discussed.
Atomistic structures and dynamics of prenucleation clusters in MOF-2 and MOF-5 syntheses
Authors: Xing Junfei , Schweighauser Luca , Okada Satoshi , Harano Koji , Nakamura Eiichi 
Published: August 2019

AbstractChemical reactions in solution almost always take place via a series of minute intermediates that are often in rapid equilibrium with each other, and hence hardly characterizable at the level of atomistic molecular structures. We found that single-molecule atomic-resolution real-time electron microscopic (SMART-EM) video imaging provides a unique methodology for capturing and analyzing the minute reaction intermediates, as illustrated here for single prenucleation clusters (PNCs) in the reaction mixture of metal–organic frameworks (MOFs). Specifically, we found two different types of PNCs are involved in the formation of MOF-2 and MOF-5 from a mixture of zinc nitrate and benzene dicarboxylates at 95 °C and 120 °C, respectively. SMART-EM identified a small amount of 1-nm-sized cube and cube-like PNCs in the MOF-5 synthesis, but not in the MOF-2 synthesis. In the latter, we instead found only linear and square PNCs, suggesting that the MOF-2/-5 bifurcation takes place at the PNC stage.
Bacteria evoke alarm behaviour in zebrafish
Authors: Chia Joanne Shu Ming , Wall Elena S. , Wee Caroline Lei , Rowland Thomas A. J. , Cheng Ruey-Kuang , Cheow Kathleen , Guillemin Karen , Jesuthasan Suresh 
Published: August 2019

AbstractWhen injured, fish release an alarm substance (Schreckstoff) that elicits fear in members of their shoal. Although Schreckstoff has been proposed to be produced by club cells in the skin, several observations indicate that these giant cells function primarily in immunity. Previous data indicate that the alarm substance can be isolated from mucus. Here we show that mucus, as well as bacteria, are transported from the external surface into club cells, by cytoplasmic transfer or invasion of cells, including neutrophils. The presence of bacteria inside club cells raises the possibility that the alarm substance may contain a bacterial component. Indeed, lysate from a zebrafishStaphylococcusisolate is sufficient to elicit alarm behaviour, acting in concert with a substance from fish. These results suggest that Schreckstoff, which allows one individual to unwittingly change the emotional state of the surrounding population, derives from two kingdoms and is associated with processes that protect the host from bacteria.
Self-organized formation of developing appendages from murine pluripotent stem cells
Authors: Mori Shunsuke , Sakakura Eriko , Tsunekawa Yuji , Hagiwara Masaya , Suzuki Takayuki , Eiraku Mototsugu 
Published: August 2019

AbstractLimb development starts with the formation of limb buds (LBs), which consist of tissues from two different germ layers; the lateral plate mesoderm-derived mesenchyme and ectoderm-derived surface epithelium. Here, we report means for induction of an LB-like mesenchymal/epithelial complex tissues from murine pluripotent stem cells (PSCs) in vitro. The LB-like tissues selectively differentiate into forelimb- or hindlimb-type mesenchymes, depending on a concentration of retinoic acid. Comparative transcriptome analysis reveals that the LB-like tissues show similar gene expression pattern to that seen in LBs. We also show that manipulating BMP signaling enables us to induce a thickened epithelial structure similar to the apical ectodermal ridge. Finally, we demonstrate that the induced tissues can contribute to endogenous digit tissue after transplantation. This PSC technology offers a first step for creating an artificial limb bud in culture and might open the door to inducing other mesenchymal/epithelial complex tissues from PSCs.
Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy
Authors: Yong Tuying , Zhang Xiaoqiong , Bie Nana , Zhang Hongbo , Zhang Xuting , Li Fuying , Hakeem Abdul , Hu Jun , Gan Lu , Santos Hélder A. , Yang Xiangliang 
Published: August 2019

AbstractDeveloping biomimetic nanoparticles without loss of the integrity of proteins remains a major challenge in cancer chemotherapy. Here, we develop a biocompatible tumor-cell-exocytosed exosome-biomimetic porous silicon nanoparticles (PSiNPs) as drug carrier for targeted cancer chemotherapy. Exosome-sheathed doxorubicin-loaded PSiNPs (DOX@E-PSiNPs), generated by exocytosis of the endocytosed DOX-loaded PSiNPs from tumor cells, exhibit enhanced tumor accumulation, extravasation from blood vessels and penetration into deep tumor parenchyma following intravenous administration. In addition, DOX@E-PSiNPs, regardless of their origin, possess significant cellular uptake and cytotoxicity in both bulk cancer cells and cancer stem cells (CSCs). These properties endow DOX@E-PSiNPs with great in vivo enrichment in total tumor cells and side population cells with features of CSCs, resulting in anticancer activity and CSCs reduction in subcutaneous, orthotopic and metastatic tumor models. These results provide a proof-of-concept for the use of exosome-biomimetic nanoparticles exocytosed from tumor cells as a promising drug carrier for efficient cancer chemotherapy.
Spectroscopic studies of atomic defects and bandgap renormalization in semiconducting monolayer transition metal dichalcogenides
Authors: Jeong Tae Young , Kim Hakseong , Choi Sang-Jun , Watanabe Kenji , Taniguchi Takashi , Yee Ki Ju , Kim Yong-Sung , Jung Suyong 
Published: August 2019

AbstractAssessing atomic defect states and their ramifications on the electronic properties of two-dimensional van der Waals semiconducting transition metal dichalcogenides (SC-TMDs) is the primary task to expedite multi-disciplinary efforts in the promotion of next-generation electrical and optical device applications utilizing these low-dimensional materials. Here, with electron tunneling and optical spectroscopy measurements with density functional theory, we spectroscopically locate the mid-gap states from chalcogen-atom vacancies in four representative monolayer SC-TMDs—WS2, MoS2, WSe2, and MoSe2—, and carefully analyze the similarities and dissimilarities of the atomic defects in four distinctive materials regarding the physical origins of the missing chalcogen atoms and the implications to SC-mTMD properties. In addition, we address both quasiparticle and optical energy gaps of the SC-mTMD films and find out many-body interactions significantly enlarge the quasiparticle energy gaps and excitonic binding energies, when the semiconducting monolayers are encapsulated by non-interacting hexagonal boron nitride layers.
Modulation of actin polymerization affects nucleocytoplasmic transport in multiple forms of amyotrophic lateral sclerosis
Authors: Giampetruzzi Anthony , Danielson Eric W. , Gumina Valentina , Jeon Maryangel , Boopathy Sivakumar , Brown Robert H. , Ratti Antonia , Landers John E. , Fallini Claudia 
Published: August 2019

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of unknown etiology. Although defects in nucleocytoplasmic transport (NCT) may be central to the pathogenesis of ALS and other neurodegenerative diseases, the molecular mechanisms modulating the nuclear pore function are still largely unknown. Here we show that genetic and pharmacological modulation of actin polymerization disrupts nuclear pore integrity, nuclear import, and downstream pathways such as mRNA post-transcriptional regulation. Importantly, we demonstrate that modulation of actin homeostasis can rescue nuclear pore instability and dysfunction caused by mutant PFN1 as well as by C9ORF72 repeat expansion, the most common mutation in ALS patients. Collectively, our data link NCT defects to ALS-associated cellular pathology and propose the regulation of actin homeostasis as a novel therapeutic strategy for ALS and other neurodegenerative diseases.
Integrative transcriptome imputation reveals tissue-specific and shared biological mechanisms mediating susceptibility to complex traits
Authors: Zhang Wen , Voloudakis Georgios , Rajagopal Veera M. , Readhead Ben , Dudley Joel T. , Schadt Eric E. , Björkegren Johan L. M. , Kim Yungil , Fullard John F. , Hoffman Gabriel E. , Roussos Panos 
Published: August 2019

AbstractTranscriptome-wide association studies integrate gene expression data with common risk variation to identify gene-trait associations. By incorporating epigenome data to estimate the functional importance of genetic variation on gene expression, we generate a small but significant improvement in the accuracy of transcriptome prediction and increase the power to detect significant expression-trait associations. Joint analysis of 14 large-scale transcriptome datasets and 58 traits identify 13,724 significant expression-trait associations that converge on biological processes and relevant phenotypes in human and mouse phenotype databases. We perform drug repurposing analysis and identify compounds that mimic, or reverse, trait-specific changes. We identify genes that exhibit agonistic pleiotropy for genetically correlated traits that converge on shared biological pathways and elucidate distinct processes in disease etiopathogenesis. Overall, this comprehensive analysis provides insight into the specificity and convergence of gene expression on susceptibility to complex traits.
Bio-mediated synthesis of 5-FU based nanoparticles employing orange fruit juice: a novel drug delivery system to treat skin fibrosarcoma in model animals
Authors: Mohammad Owais , Faisal Syed Mohd. , Ahmad Nadeem , Rauf Mohd. Ahmar , Umar Mohd Saad , Mujeeb Anzar Abdul , Pachauri Piyush , Ahmed Anees , Kashif Mohammad , Ajmal Mohammad , Zubair Swaleha 
Published: August 2019

AbstractNano-sized drug delivery systems (NDDS) have been widely exploited to achieve targeted delivery of pharmaco-materials. Traditional pharmaceutical approaches, implied in the synthesis of nano-formulations, are obscure owing to the incompatible physico-chemical properties of the core drug as well as some other factors crucial in development of NDDS. Infact, most of the existing methods used in development of NDDS rely on usage of additives or excipients, a special class of chemicals. Barring few exceptions, the usage of synthetic excipients ought to be curtailed because of several associated undesirable features. Such issues necessitate strategies that lead to development of the synthetic excipient free drug delivery system. Plant based extracts have great potential to induce synthesis of nano-sized particles. Considering this fact, here we propose a prototype employing orange fruit juice (OJ) to facilitate bio-mediated synthesis of nano-sized supra-molecular assemblies of 5-fluorouracil (5-FU), a potent anticancer drug. The as-synthesized 5-FU Nanoparticles (NPs) retained the anti-neoplastic efficacy of the parent compound and induced apoptosis in cancer cells. The novel 5-FU NPs formulation demonstrated enhanced efficacy against DMBA induced experimental fibrosarcoma in the mouse model when compared to the micro-sized crystals of parent 5-FU drug.
Hepsin-mediated Processing of Uromodulin is Crucial for Salt-sensitivity and Thick Ascending Limb Homeostasis
Authors: Olinger Eric , Lake Jennifer , Sheehan Susan , Schiano Guglielmo , Takata Tomoaki , Tokonami Natsuko , Debaix Huguette , Consolato Francesco , Rampoldi Luca , Korstanje Ron , Devuyst Olivier 
Published: August 2019

AbstractUromodulin is a zona pellucida-type protein essentially produced in the thick ascending limb (TAL) of the mammalian kidney. It is the most abundant protein in normal urine. Defective uromodulin processing is associated with various kidney disorders. The luminal release and subsequent polymerization of uromodulin depend on its cleavage mediated by the serine protease hepsin. The biological relevance of a proper cleavage of uromodulin remains unknown. Here we combinedin vivotesting on hepsin-deficient mice,ex vivoanalyses on isolated tubules andin vitrostudies on TAL cells to demonstrate that hepsin influence on uromodulin processing is an important modulator of salt transport via the sodium cotransporter NKCC2 in the TAL. At baseline, hepsin-deficient mice accumulate uromodulin, along with hyperactivated NKCC2, resulting in a positive sodium balance and a better adaptation to water deprivation. In conditions of high salt intake, defective uromodulin processing predisposes hepsin-deficient mice to a salt-wasting phenotype, with a decreased salt sensitivity. These modifications are associated with intracellular accumulation of uromodulin, endoplasmic reticulum-stress and signs of tubular damage. These studies expand the physiological role of hepsin and uromodulin and highlight the importance of hepsin-mediated processing of uromodulin for kidney tubule homeostasis and salt sensitivity.
Nanoscale Spatially Resolved Mapping of Uranium Enrichment
Authors: Kautz Elizabeth , Burkes Douglas , Joshi Vineet , Lavender Curt , Devaraj Arun 
Published: August 2019

AbstractSpatially resolved analysis of uranium (U) isotopes in small volumes of actinide-bearing materials is critical for a variety of technical disciplines, including earth and planetary sciences, environmental monitoring, bioremediation, and the nuclear fuel cycle. However, achieving subnanometer-scale spatial resolution for such isotopic analysis is currently a challenge. By using atom probe tomography—a three-dimensional nanoscale characterisation technique—we demonstrate unprecedented nanoscale mapping of U isotopic enrichment with high sensitivity across various microstructural interfaces within small volumes (~100 nm3) of depleted and low-enriched U alloyed with 10 wt% molybdenum that has different nominal enrichments of 0.20 and 19.75% 235U, respectively. We map enrichment in various morphologies of a U carbide phase, the adjacent γ-UMo matrix, and across interfaces (e.g., carbide/matrix, grain boundary). Results indicate the U carbides were formed during casting, rather than retained from either highly enriched or depleted U feedstock materials. The approach presented here can be applied to study nanoscale variations of isotopic abundances in the broad class of actinide-bearing materials, providing unique insights into their origins and thermomechanical processing routes.
Heavy fermion quantum criticality at dilute carrier limit in CeNi2−δ(As1−xPx)2
Authors: Chen Jian , Wang Zhen , Li Yupeng , Feng Chunmu , Dai Jianhui , Xu Zhu’an , Si Qimiao 
Published: August 2019

AbstractWe study the quantum phase transitions in the nickel pnctides, CeNi2−δ(As1−xPx)2 (δ ≈ 0.07–0.22) polycrystalline samples. This series displays the distinct heavy fermion behavior in the rarely studied parameter regime of dilute carrier limit. We systematically investigate the magnetization, specific heat and electrical transport down to low temperatures. Upon increasing the P-content, the antiferromagnetic order of the Ce-4f moment is suppressed continuously and vanishes at xc ~ 0.55. At this doping, the temperature dependences of the specific heat and longitudinal resistivity display non-Fermi liquid behavior. Both the residual resistivity ρ0 and the Sommerfeld coefficient γ0 are sharply peaked around xc. When the P-content reaches close to 100%, we observe a clear low-temperature crossover into the Fermi liquid regime. In contrast to what happens in the parent compound x = 0.0 as a function of pressure, we find a surprising result that the non-Fermi liquid behavior persists over a nonzero range of doping concentration, xc < x < 0.9. In this doping range, at the lowest measured temperatures, the temperature dependence of the specific-heat coefficient is logarithmically divergent and that of the electrical resistivity is linear. We discuss the properties of CeNi2−δ(As1−xPx)2 in comparison with those of its 1111 counterpart, CeNi(As1−xPx)O. Our results indicate a non-Fermi liquid phase in the global phase diagram of heavy fermion metals.
Hyperbaric therapy provides no benefit for skeletal muscle and respiratory function and accelerates cardiac injury in mdx mice
Authors: Fischer Kaleb D. , Heitzman Jackie A. , Townsend DeWayne 
Published: August 2019

AbstractDuchenne muscular dystrophy (DMD) is a uniformly fatal condition of striated muscle wasting resulting in premature death from respiratory and/or cardiac failure. Symptomatic therapy has prolonged survival by limiting deaths resulting from respiratory insufficiency, but there is currently no effective therapy for most patients with DMD. This grim prognosis has led patients and their families to seek unproven therapeutic approaches. One such approach is the use of hyperbaric therapies, which 14% of DMD patients self-report using. The primary goal of this study was to determine if intermittent hyperbaric exposure altered the muscle function of the mdx mouse, a genetic model of DMD. To do this, mdx mice were exposed to three daily 90-minute 1.3 atmosphere hyperbaric exposures for 4 weeks. Skeletal muscle, respiratory, and cardiac function were assessed in treated and untreated wild type and dystrophic mice. The results of these studies find that hyperbaric and hyperoxic approaches resulted in increased cardiac fibrosis in dystrophic mice and no beneficial effects on the functional parameters measured. These data suggest that these oxygen-based therapies are unlikely to provide therapeutic benefit to DMD patients.
Comparative transcriptome and metabolite profiling of four tissues from Alisma orientale (Sam.) Juzep reveals its inflorescence developmental and medicinal characteristics
Authors: Lin Wenjin , Sun Fengling , Zhang Yamin , Xu Xiaomei , Lu Xuehua , Li Lisha , Xu Rongqing 
Published: August 2019

AbstractAlisma orientale (Sam.) Juzep (A. orientale) is an important medicinal plant in traditional Chinese medicine. In this study, de novo RNA-seq of A. orientale was performed based on the cDNA libraries from four different tissues, roots, leaves, scapes and inflorescences. A total of 41,685 unigenes were assembled, 25,024 unigene functional annotations were obtained by searching against the five public sequence databases, and 3,411 simple sequence repeats in A. orientale were reported for the first time. 15,402 differentially expressed genes were analysed. The morphological characteristics showed that compared to the other tissues, the leaves had more chlorophyll, the scapes had more vascular bundles, and the inflorescences contained more starch granules and protein. In addition, the metabolic profiles of eight kinds of alisols metabolite profiling, which were measured by ultra-Performance liquid chromatography-triple quadrupole-mass spectrometry showed that alisol B 23-acetate and alisol B were the major components of the four tissues at amounts of 0.068~0.350 mg/g and 0.046~0.587 mg/g, respectively. In addition, qRT-PCR validated that farnesyl pyrophosphate synthase and 3-hydroxy-3-methylglutaryl-CoA reductase should be considered the critical candidate genes involved in alisol biosynthesis. These transcriptome and metabolic profiles of A. orientale may help clarify the molecular mechanisms underlying the medicinal characteristics of A. orientale.
Hexagonal Close-packed Iron Hydride behind the Conventional Phase Diagram
Authors: Machida Akihiko , Saitoh Hiroyuki , Hattori Takanori , Sano-Furukawa Asami , Funakoshi Ken-ichi , Sato Toyoto , Orimo Shin-ichi , Aoki Katsutoshi 
Published: August 2019

AbstractHexagonal close-packed iron hydride, hcp FeHx, is absent from the conventional phase diagram of the Fe–H system, although hcp metallic Fe exists stably over extensive temperature (T) and pressure (P) conditions, including those corresponding to the Earth’s inner core. In situ X-ray and neutron diffraction measurements at temperatures ranging from 298 to 1073 K and H pressures ranging from 4 to 7 GPa revealed that the hcp hydride was formed for FeHx compositions when x < 0.6. Hydrogen atoms occupied the octahedral interstitial sites of the host metal lattice both partially and randomly. The hcp hydride exhibited a H-induced volume expansion of 2.48(5) Å3/H-atom, which was larger than that of the face-centered cubic (fcc) hydride. The hcp hydride showed an increase in x with T, whereas the fcc hydride showed a corresponding decrease. The present study provides guidance for further investigations of the Fe–H system over an extensive x–T–P region.
MT2A is an early predictive biomarker of response to chemotherapy and a potential therapeutic target in osteosarcoma
Authors: Mangelinck Adèle , da Costa Maria Eugénia Marques , Stefanovska Bojana , Bawa Olivia , Polrot Mélanie , Gaspar Nathalie , Fromigué Olivia 
Published: August 2019

AbstractOsteosarcoma is the most prevalent primary bone malignancy in children and young adults. Resistance to chemotherapy remains a key challenge for effective treatment of patients with osteosarcoma. The aim of the present study was to investigate the preventive role of metallothionein-2A (MT2A) in response to cytotoxic effects of chemotherapy. A panel of human and murine osteosarcoma cell lines, modified for MT2A were evaluated for cell viability, and motility (wound healing assay). Cell-derived xenograft models were established in mice. FFPE tumour samples were assessed by IHC. In vitro experiments indicated a positive correlation between half-maximal inhibitory concentration (IC50) for drugs in clinical practice, and MT2A mRNA level. This reinforced our previously reported correlation between MT2A mRNA level in tumour samples at diagnosis and overall survival in patients with osteosarcoma. In addition, MT2A/MT2 silencing using shRNA strategy led to a marked reduction of IC50 values and to enhanced cytotoxic effect of chemotherapy on primary tumour. Our results show that MT2A level could be used as a predictive biomarker of resistance to chemotherapy, and provide with preclinical rational for MT2A targeting as a therapeutic strategy for enhancing anti-tumour treatment of innate chemo-resistant osteosarcoma cells.