bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-nuclei RNA-seq on human retinal tissue provides improved transcriptome profiling
Authors: Liang Qingnan , Dharmat Rachayata , Owen Leah , Shakoor Akbar , Li Yumei , Kim Sangbae , Vitale Albert , Kim Ivana , Morgan Denise , Liang Shaoheng , Wu Nathaniel , Chen Ken , DeAngelis Margaret M. , Chen Rui 
Published: December 2019

AbstractSingle-cell RNA-seq is a powerful tool in decoding the heterogeneity in complex tissues by generating transcriptomic profiles of the individual cell. Here, we report a single-nuclei RNA-seq (snRNA-seq) transcriptomic study on human retinal tissue, which is composed of multiple cell types with distinct functions. Six samples from three healthy donors are profiled and high-quality RNA-seq data is obtained for 5873 single nuclei. All major retinal cell types are observed and marker genes for each cell type are identified. The gene expression of the macular and peripheral retina is compared to each other at cell-type level. Furthermore, our dataset shows an improved power for prioritizing genes associated with human retinal diseases compared to both mouse single-cell RNA-seq and human bulk RNA-seq results. In conclusion, we demonstrate that obtaining single cell transcriptomes from human frozen tissues can provide insight missed by either human bulk RNA-seq or animal models.
Multi-scale imaging and analysis identify pan-embryo cell dynamics of germlayer formation in zebrafish
Authors: Shah Gopi , Thierbach Konstantin , Schmid Benjamin , Waschke Johannes , Reade Anna , Hlawitschka Mario , Roeder Ingo , Scherf Nico , Huisken Jan 
Published: December 2019

AbstractThe coordination of cell movements across spatio-temporal scales ensures precise positioning of organs during vertebrate gastrulation. Mechanisms governing such morphogenetic movements have been studied only within a local region, a single germlayer or in whole embryos without cell identity. Scale-bridging imaging and automated analysis of cell dynamics are needed for a deeper understanding of tissue formation during gastrulation. Here, we report pan-embryo analyses of formation and dynamics of all three germlayers simultaneously within a developing zebrafish embryo. We show that a distinct distribution of cells in each germlayer is established during early gastrulation via cell movement characteristics that are predominantly determined by their position in the embryo. The differences in initial germlayer distributions are subsequently amplified by a global movement, which organizes the organ precursors along the embryonic body axis, giving rise to the blueprint of organ formation. The tools and data are available as a resource for the community.
In vitro implementation of robust gene regulation in a synthetic biomolecular integral controller
Authors: Agrawal Deepak K. , Marshall Ryan , Noireaux Vincent , Sontag Eduardo D 
Published: December 2019

AbstractFeedback mechanisms play a critical role in the maintenance of cell homeostasis in the presence of disturbances and uncertainties. Motivated by the need to tune the dynamics and improve the robustness of gene circuits, biological engineers have proposed various designs that mimic natural molecular feedback control mechanisms. However, practical and predictable implementations have proved challenging because of the complexity of synthesis and analysis of complex biomolecular networks. Here, we analyze and experimentally validate a synthetic biomolecular controller executed in vitro. The controller ensures that gene expression rate tracks an externally imposed reference level, and achieves this goal even in the presence of certain kinds of disturbances. Our design relies upon an analog of the well-known principle of integral feedback in control theory. We implement the controller in an Escherichia coli cell-free transcription-translation system, which allows rapid prototyping and implementation. Modeling and theory guide experimental implementation with well-defined operational predictability.
Wireless, battery-free, fully implantable multimodal and multisite pacemakers for applications in small animal models
Authors: Gutruf Philipp , Yin Rose T. , Lee K. Benjamin , Ausra Jokubas , Brennan Jaclyn A. , Qiao Yun , Xie Zhaoqian , Peralta Roberto , Talarico Olivia , Murillo Alejandro , Chen Sheena W. , Leshock John P. , Haney Chad R. , Waters Emily A. , Zhang Changxing , Luan Haiwen , Huang Yonggang , Trachiotis Gregory , Efimov Igor R. , Rogers John A. 
Published: December 2019

AbstractSmall animals support a wide range of pathological phenotypes and genotypes as versatile, affordable models for pathogenesis of cardiovascular diseases and for exploration of strategies in electrotherapy, gene therapy, and optogenetics. Pacing tools in such contexts are currently limited to tethered embodiments that constrain animal behaviors and experimental designs. Here, we introduce a highly miniaturized wireless energy-harvesting and digital communication electronics for thin, miniaturized pacing platforms weighing 110 mg with capabilities for subdermal implantation and tolerance to over 200,000 multiaxial cycles of strain without degradation in electrical or optical performance. Multimodal and multisite pacing in ex vivo and in vivo studies over many days demonstrate chronic stability and excellent biocompatibility. Optogenetic stimulation of cardiac cycles with in-animal control and induction of heart failure through chronic pacing serve as examples of modes of operation relevant to fundamental and applied cardiovascular research and biomedical technology.
Artificially cloaked viral nanovaccine for cancer immunotherapy
Authors: Fusciello Manlio , Fontana Flavia , Tähtinen Siri , Capasso Cristian , Feola Sara , Martins Beatriz , Chiaro Jacopo , Peltonen Karita , Ylösmäki Leena , Ylösmäki Erkko , Hamdan Firas , Kari Otto K. , Ndika Joseph , Alenius Harri , Urtti Arto , Hirvonen Jouni T. , Santos Hélder A. , Cerullo Vincenzo 
Published: December 2019

AbstractVirus-based cancer vaccines are nowadays considered an interesting approach in the field of cancer immunotherapy, despite the observation that the majority of the immune responses they elicit are against the virus and not against the tumor. In contrast, targeting tumor associated antigens is effective, however the identification of these antigens remains challenging. Here, we describe ExtraCRAd, a multi-vaccination strategy focused on an oncolytic virus artificially wrapped with tumor cancer membranes carrying tumor antigens. We demonstrate that ExtraCRAd displays increased infectivity and oncolytic effect in vitro and in vivo. We show that this nanoparticle platform controls the growth of aggressive melanoma and lung tumors in vivo both in preventive and therapeutic setting, creating a highly specific anti-cancer immune response. In conclusion, ExtraCRAd might serve as the next generation of personalized cancer vaccines with enhanced features over standard vaccination regimens, representing an alternative way to target cancer.
An artificial metalloenzyme biosensor can detect ethylene gas in fruits and Arabidopsis leaves
Authors: Vong Kenward , Eda Shohei , Kadota Yasuhiro , Nasibullin Igor , Wakatake Takanori , Yokoshima Satoshi , Shirasu Ken , Tanaka Katsunori 
Published: December 2019

AbstractEnzyme biosensors are useful tools that can monitor rapid changes in metabolite levels in real-time. However, current approaches are largely constrained to metabolites within a limited chemical space. With the rising development of artificial metalloenzymes (ArM), a unique opportunity exists to design biosensors from the ground-up for metabolites that are difficult to detect using current technologies. Here we present the design and development of the ArM ethylene probe (AEP), where an albumin scaffold is used to solubilize and protect a quenched ruthenium catalyst. In the presence of the phytohormone ethylene, cross metathesis can occur to produce fluorescence. The probe can be used to detect both exogenous- and endogenous-induced changes to ethylene biosynthesis in fruits and leaves. Overall, this work represents an example of an ArM biosensor, designed specifically for the spatial and temporal detection of a biological metabolite previously not accessible using enzyme biosensors.
Enhanced control of self-doping in halide perovskites for improved thermoelectric performance
Authors: Liu Tianjun , Zhao Xiaoming , Li Jianwei , Liu Zilu , Liscio Fabiola , Milita Silvia , Schroeder Bob C. , Fenwick Oliver 
Published: December 2019

AbstractMetal halide perovskites have emerged as promising photovoltaic materials, but, despite ultralow thermal conductivity, progress on developing them for thermoelectrics has been limited. Here, we report the thermoelectric properties of all-inorganic tin based perovskites with enhanced air stability. Fine tuning the thermoelectric properties of the films is achieved by self-doping through the oxidation of tin (ΙΙ) to tin (ΙV) in a thin surface-layer that transfers charge to the bulk. This separates the doping defects from the transport region, enabling enhanced electrical conductivity. We show that this arises due to a chlorine-rich surface layer that acts simultaneously as the source of free charges and a sacrificial layer protecting the bulk from oxidation. Moreover, we achieve a figure-of-merit (ZT) of 0.14 ± 0.01 when chlorine-doping and degree of the oxidation are optimised in tandem.
Solving the controversy of healthier organic fruit: Leaf wounding triggers distant gene expression response of polyphenol biosynthesis in strawberry fruit (Fragaria x ananassa)
Authors: Ibanez Facundo , Bang Woo Young , Lombardini Leonardo , Cisneros-Zevallos Luis 
Published: December 2019

AbstractThe claim that organic agriculture produces higher levels of phytochemicals has been controversial for decades. Using strawberries as a model crop in field conditions, a preharvest leaf wounding stress was applied to study the production of phytochemicals in fruits. As a result phenolic compounds (PCs) and total soluble sugars increased significantly, where specific phenylpropanoids showed increment up to 137% and several genes related to PCs biosynthesis and sugar transport were overexpressed. It was observed that the accumulation of PCs on fruits can be triggered by the application of wounding stress in a distant tissue and this accumulation is directly related to carbon partition and associated gene expression. This supports the idea that higher levels of healthy phytochemicals reported in organic fruits and vegetables could be due to the wounding component of the biotic stress attributed to insects to which the plant are exposed to.
NAC-Like Gene GIBBERELLIN SUPPRESSING FACTOR Regulates the Gibberellin Metabolic Pathway in Response to Cold and Drought Stresses in Arabidopsis
Authors: Chen Hong-Ie , Li Pei-Fang , Yang Chang-Hsien 
Published: December 2019

AbstractTo investigate the functions ofNAC-like genes, we reported the characterization and functional analysis of oneArabidopsis NAC-like gene which showed a novel function in the regulation of gibberellin biosynthesis and named asGIBBERELLIN SUPPRESSING FACTOR(GSF). GSF acts as a transcriptional activator and has transactivation capacity based on yeast transcription activity assays. YFP + GSF-TM (lacking a transmembrane domain) fusion proteins accumulated in the nuclei, while the YFP + GSF fusion proteins only accumulated in the ER membrane and were absent from the nuclei. These results revealed that GSF requires processing and release from the ER and transportation into the nucleus to perform its function. The ectopic expression ofGSF-TMcaused a dwarfism phenotype, which was correlated with the upregulation of the gibberellin (GA) deactivation genes GA2-oxidases 2/6 (GA2ox2/6) and the downregulation of the GA biosynthetic genes GA20-oxidases 1–4 (GA20ox1-4). The external application of GA rescued the dwarfism in the 35 S::GSF-TMplants, indicating thatGSFaffects GA biosynthesis, rather than the GA signaling pathway. Further analysis indicated that the upregulation ofGA2ox2/6is a key factor for theGSFfunction to regulate the GA level, since 35 S::GA20ox1could not rescue the dwarfism in the 35 S::GSF-TMplants. Cold treatment induced the processing of the YFP + GSF fusion proteins from the ER membrane and their entry into the nuclei, which is correlated with the cold-induced upregulation of GA2oxs. In addition, the expression of GA2oxs was induced by drought, and the 35 S::GSF-TMplants showed drought tolerance compared to the wild-type plants. Our data suggest a role forGSFin response to abiotic stresses, such as cold and drought, by suppressing the biosynthesis of GA in Arabidopsis.
Insight into the biology of Mycobacterium mucogenicum and Mycobacterium neoaurum clade members
Authors: Behra Phani Rama Krishna , Pettersson B. M. Fredrik , Ramesh Malavika , Dasgupta Santanu , Kirsebom Leif A. 
Published: December 2019

AbstractNontuberculous mycobacteria, NTM, are of growing concern and among these members of the Mycobacterium mucogenicum (Mmuc) and Mycobacterium neoaurum (Mneo) clades can cause infections in humans and they are resistant to first-line anti-tuberculosis drugs. They can be isolated from different ecological niches such as soil, tap water and ground water. Mycobacteria, such as Mmuc and Mneo, are classified as rapid growing mycobacteria, RGM, while the most familiar, Mycobacterium tuberculosis, belongs to the slow growing mycobacteria, SGM. Modern “omics” approaches have provided new insights into our understanding of the biology and evolution of this group of bacteria. Here we present comparative genomics data for seventeen NTM of which sixteen belong to the Mmuc- and Mneo-clades. Focusing on virulence genes, including genes encoding sigma/anti-sigma factors, serine threonine protein kinases (STPK), type VII (ESX genes) secretion systems and mammalian cell entry (Mce) factors we provide insight into their presence as well as phylogenetic relationship in the case of the sigma/anti-sigma factors and STPKs. Our data further suggest that these NTM lack ESX-5 and Mce2 genes, which are known to affect virulence. In this context, Mmuc- and Mneo-clade members lack several of the genes in the glycopeptidolipid (GLP) locus, which have roles in colony morphotype appearance and virulence. For the M. mucogenicum type strain, MmucT, we provide RNASeq data focusing on mRNA levels for sigma factors, STPK, ESX proteins and Mce proteins. These data are discussed and compared to in particular the SGM and fish pathogen Mycobacterium marinum. Finally, we provide insight into as to why members of the Mmuc- and Mneo-clades show resistance to rifampin and isoniazid, and why MmucT forms a rough colony morphotype.
Biodegradation of Vulcanized SBR: A Comparison between Bacillus subtilis, Pseudomonas aeruginosa and Streptomyces sp
Authors: Aboelkheir Mostafa Galal , Bedor Priscilla Braga , Leite Selma Gomes , Pal Kaushik , Toledo Filho Romildo Dias , Gomes de Souza Fernando 
Published: December 2019

AbstractRubber residues present harmful impacts on health and environment, besides wasting valuable and huge amounts of rubber. Biological recycling technique is focused here to minimize this problem. A comparison of the biodegradation effect caused by Bacillus subtilis, Pseudomonas aeruginosa, and Streptomyces sp., separately, on vulcanized SBR-rubber during 4 weeks is reported. The surface and molecular analyses were studied by FTIR-ATR, TGA, DSC, TC and SEM/EDS, in addition to the contact angle and crosslinking tests. B. subtilis, P. aeruginosa, and Streptomyces sp. evoked after 4 weeks a loss in v-SBR crosslinks by 17.15, 10.68 and 43.39% and also in the contact angle with water by 14.10, 12.86 and 15.71%, respectively., if compared to Control samples. FTIR findings indicate that the polymeric chain has been partially consumed causing C-C bonds scission indicating the biodegradation and bio-devulcanization phenomena. The bacterial strains caused a carbon loss by 9.15, 5.97 and 4.55% after one week and 16.09, 16.79 and 18.13% after four weeks for B. subtilis, P. aeruginosa, and Streptomyces sp. mediums, respectively. DSC and EDS results are also promising and highlighting Streptomyces sp. strain as the most effective biodegradative one as an alternative and natural mean of degrading vulcanized rubber residues.
Radiotherapy was associated with the lower incidence of metachronous second primary lung cancer
Authors: Hu Zhi Gang , Tian Yu Feng , Li Wen Xin , Zeng Fan Jun 
Published: December 2019

AbstractOur study aims to estimate the incidence of metachronous second primary lung cancer(SPLC) in initial primary lung cancer(IPLC) survivors and to determine whether radiotherapy affects the risk of metachronous SPLC in the first five years after the diagnosis of lung cancer. Incidence data of IPLC individuals who survived ≥2 years were obtained from SEER-18 database in 2004–2007. Joinpoint regression analysis and competing risk analysis were used to calculate the incidence of metachronous SPLC. Propensity score matching and decision analysis were available to estimate the effect of radiotherapy on metachronous SPLC. 264 of 11657 IPLC survivors with radiotherapy and 1090 of 24499 IPLC survivors without radiotherapy developed metachronous SPLC during 5-year follow-up, respectively. In joinpoint regression analysis, the 5-year incidence of metachronous SPLC in the radiotherapy group was lower than that in the nonradiotherapy group(2385 per 100,000 vs 4748 per 100,000, HR = 0.43,95% CI:0.39–0.47). Competing risk analysis showed that the survivors with radiotherapy were associated with the lower 5 year incidence of metachronous SPLC compared with those without radiotherapy(2.28% vs 4.47%, HR = 0.49,95% CI:0.43–0.57). Through propensity score matching, 4077 pairs of survivors were available to further study that radiotherapy potentially decreased the risk of developing metachronous SPLC with the adjustment of various factors(2.5% vs 3.3%, HR = 0.72, 95% CI:0.55–0.96). Decision analysis suggested that radiotherapy was a negative independent risk factor of metachronous SPLC with clinical net benefit in a range of risk thresholds (2% to 5%). Survivors of IPLC with radiotherapy likely had a low risk of metachronous SPLC during the first five years follow-up, especially non-small cell lung cancer.
Study of temporal variability of salivary cortisol and cortisone by LC-MS/MS using a new atmospheric pressure ionization source
Authors: Bakusic Jelena , De Nys Siemon , Creta Matteo , Godderis Lode , Duca Radu Corneliu 
Published: December 2019

AbstractThere is a growing interest concerning the relevance of salivary cortisone levels in stress-related research. However, studies investigating morning patterns and day-to-day variability of cortisone versus cortisol levels are lacking. Cortisol and cortisone analysis by liquid chromatography-tandem mass spectroscopy (LC-MS/MS) has been widely used for routine laboratory measurements in the last years. The aim of this study was to develop an ultra-performance LC-MS/MS method for the simultaneous quantification of salivary cortisol and cortisone levels for assessing the temporal variability of these hormones. Saliva samples were collected from 18 healthy volunteers at 0, 15, and 30 min after awakening on each day for 1 week and analysed with the newly developed method. We used a novel atmospheric pressure ionization source, which resulted in high sensitivity and specificity for both cortisol and cortisone as well as higher peak values and signal-to-noise ratio as compared with the electrospray ionization source. Cortisone showed similar morning patterns as cortisol: a 25% and 49% increase in levels at 15 and 30 min after awakening, respectively. Most cortisone indices showed somewhat lower day-to-day variability and were less affected by state-related covariates. We recommend further exploration of the potential of salivary cortisone as a biomarker in stress-related research.
Assessing the therapeutic potential of Graptopetalum paraguayense on Alzheimer’s disease using patient iPSC-derived neurons
Authors: Wu Pei-Chun , Fann Ming-Ji , Tran Tu Thanh , Chen Shu-Cian , Devina Tania , Cheng Irene Han-Juo , Lien Cheng-Chang , Kao Lung-Sen , Wang Shuu-Jiun , Fuh Jong-Ling , Tzeng Tsai-Teng , Huang Chi-Ying , Shiao Young-Ji , Wong Yu-Hui 
Published: December 2019

AbstractAlzheimer’s disease (AD) is the most common type of dementia and also one of the leading causes of death worldwide. However, the underlying mechanisms remain unclear, and currently there is no drug treatment that can prevent or cure AD. Here, we have applied the advantages of using induced pluripotent stem cell (iPSC)-derived neurons (iNs) from AD patients, which are able to offer human-specific drug responsiveness, in order to evaluate therapeutic candidates for AD. Using approach involving an inducible neurogenin-2 transgene, we have established a robust and reproducible protocol for differentiating human iPSCs into glutamatergic neurons. The AD-iN cultures that result have mature phenotypic and physiological properties, together with AD-like biochemical features that include extracellular β-amyloid (Aβ) accumulation and Tau protein phosphorylation. By screening using a gene set enrichment analysis (GSEA) approach, Graptopetalum paraguayense (GP) has been identified as a potential therapeutic agent for AD from among a range of Chinese herbal medicines. We found that administration of a GP extract caused a significantly reduction in the AD-associated phenotypes of the iNs, including decreased levels of extracellular Aβ40 and Aβ42, as well as reduced Tau protein phosphorylation at positions Ser214 and Ser396. Additionally, the effect of GP was more prominent in AD-iNs compared to non-diseased controls. These findings provide valuable information that suggests moving extracts of GP toward drug development, either for treating AD or as a health supplement to prevent AD. Furthermore, our human iN-based platform promises to be a useful strategy when it is used for AD drug discovery.
I8-arachnotocin–an arthropod-derived G protein-biased ligand of the human vasopressin V2 receptor
Authors: Duerrauer Leopold , Muratspahić Edin , Gattringer Jasmin , Keov Peter , Mendel Helen C. , Pfleger Kevin D. G. , Muttenthaler Markus , Gruber Christian W. 
Published: December 2019

AbstractThe neuropeptides oxytocin (OT) and vasopressin (VP) and their G protein-coupled receptors OTR, V1aR, V1bR, and V2R form an important and widely-distributed neuroendocrine signaling system. In mammals, this signaling system regulates water homeostasis, blood pressure, reproduction, as well as social behaviors such as pair bonding, trust and aggression. There exists high demand for ligands with differing pharmacological profiles to study the physiological and pathological functions of the individual receptor subtypes. Here, we present the pharmacological characterization of an arthropod (Metaseiulus occidentalis) OT/VP-like nonapeptide across the human OT/VP receptors. I8-arachnotocin is a full agonist with respect to second messenger signaling at human V2R (EC50 34 nM) and V1bR (EC50 1.2 µM), a partial agonist at OTR (EC50 790 nM), and a competitive antagonist at V1aR [pA2 6.25 (558 nM)]. Intriguingly, I8-arachnotocin activated the Gαs pathway of V2R without recruiting either β-arrestin-1 or β-arrestin-2. I8-arachnotocin might thus be a novel pharmacological tool to study the (patho)physiological relevance of β-arrestin-1 or -2 recruitment to the V2R. These findings furthermore highlight arthropods as a novel, vast and untapped source for the discovery of novel pharmacological probes and potential drug leads targeting neurohormone receptors.