bluuebunny/crossref_metadata_2025_split huggingface dataset:
TFAP2C facilitates somatic cell reprogramming by inhibiting c-Myc-dependent apoptosis and promoting mesenchymal-to-epithelial transition
Authors: Wang Yuan , Chen Shuang , Jiang Qingyuan , Deng Jie , Cheng Fuyi , Lin Yi , Cheng Lin , Ye Yixin , Chen Xiaolei , Yao Yunqi , Zhang Xiaomei , Shi Gang , Dai Lei , Su Xiaolan , Peng Yong , Deng Hongxin 
Published: June 2020

AbstractTranscription factors are known to mediate the conversion of somatic cells to induced pluripotent stem cells (iPSCs). Transcription factor TFAP2C plays important roles in the regulation of embryonic development and carcinogenesis; however, the roles of Tfap2c in regulating somatic cell reprogramming are not well understood. Here we demonstrate Tfap2c is induced during the generation of iPSCs from mouse fibroblasts and acts as a facilitator for iPSCs formation. Mechanistically, the c-Myc-dependent apoptosis, which is a roadblock to reprogramming, can be significantly mitigated by Tfap2c overexpression. Meanwhile, Tfap2c can greatly promote mesenchymal-to-epithelial transition (MET) at initiation stage of OSKM-induced reprogramming. Further analysis of gene expression and targets of Tfap2c during reprogramming by RNA-sequencing (RNA-seq) and ChIP-qPCR indicates that TFAP2C can promote epithelial gene expression by binding to their promoters directly. Finally, knockdown of E-cadherin (Cdh1), an important downstream target of TFAP2C and a critical regulator of MET antagonizes Tfap2c-mediated reprogramming. Taken together, we conclude that Tfap2c serves as a strong activator for somatic cell reprogramming through promoting the MET and inhibiting c-Myc-dependent apoptosis.
Amplitude and frequency sensing of microwave fields with a superconducting transmon qudit
Authors: Kristen M. , Schneider A. , Stehli A. , Wolz T. , Danilin S. , Ku H. S. , Long J. , Wu X. , Lake R. , Pappas D. P. , Ustinov A. V. , Weides M. 
Published: June 2020

AbstractExperiments with superconducting circuits require careful calibration of the applied pulses and fields over a large frequency range. This remains an ongoing challenge as commercial semiconductor electronics are not able to probe signals arriving at the chip due to its cryogenic environment. Here, we demonstrate how the on-chip amplitude and frequency of a microwave signal can be inferred from the ac Stark shifts of higher transmon levels. In our time-resolved measurements we employ Ramsey fringes, allowing us to detect the amplitude of the systems transfer function over a range of several hundreds of MHz with an energy sensitivity on the order of 10−4. Combined with similar measurements for the phase of the transfer function, our sensing method can facilitate pulse correction for high fidelity quantum gates in superconducting circuits. Additionally, the potential to characterize arbitrary microwave fields promotes applications in related areas of research, such as quantum optics or hybrid microwave systems including photonic, mechanical or magnonic subsystems.
Domain-centric database to uncover structure of minimally characterized viral genomes
Authors: Bramley John C. , Yenkin Alex L. , Zaydman Mark A. , DiAntonio Aaron , Milbrandt Jeffrey D. , Buchser William J. 
Published: June 2020

AbstractProtein domain-based approaches to analyzing sequence data are valuable tools for examining and exploring genomic architecture across genomes of different organisms. Here, we present a complete dataset of domains from the publicly available sequence data of 9,051 reference viral genomes. The data provided contain information such as sequence position and neighboring domains from 30,947 pHMM-identified domains from each reference viral genome. Domains were identified from viral whole-genome sequence using automated profile Hidden Markov Models (pHMM). This study also describes the framework for constructing “domain neighborhoods”, as well as the dataset representing it. These data can be used to examine shared and differing domain architectures across viral genomes, to elucidate potential functional properties of genes, and potentially to classify viruses.
CRISPR-Cas9 generated Pompe knock-in murine model exhibits early-onset hypertrophic cardiomyopathy and skeletal muscle weakness
Authors: Huang Jeffrey Y. , Kan Shih-Hsin , Sandfeld Emilie K. , Dalton Nancy D. , Rangel Anthony D. , Chan Yunghang , Davis-Turak Jeremy , Neumann Jon , Wang Raymond Y. 
Published: June 2020

AbstractInfantile-onset Pompe Disease (IOPD), caused by mutations in lysosomal acid alpha-glucosidase (Gaa), manifests rapidly progressive fatal cardiac and skeletal myopathy incompletely attenuated by synthetic GAA intravenous infusions. The currently available murine model does not fully simulate human IOPD, displaying skeletal myopathy with late-onset hypertrophic cardiomyopathy. Bearing a Cre-LoxP induced exonic disruption of the murine Gaa gene, this model is also not amenable to genome-editing based therapeutic approaches. We report the early onset of severe hypertrophic cardiomyopathy in a novel murine IOPD model generated utilizing CRISPR-Cas9 homology-directed recombination to harbor the orthologous Gaa mutation c.1826dupA (p.Y609*), which causes human IOPD. We demonstrate the dual sgRNA approach with a single-stranded oligonucleotide donor is highly specific for the Gaac.1826 locus without genomic off-target effects or rearrangements. Cardiac and skeletal muscle were deficient in Gaa mRNA and enzymatic activity and accumulated high levels of glycogen. The mice demonstrated skeletal muscle weakness but did not experience early mortality. Altogether, these results demonstrate that the CRISPR-Cas9 generated Gaac.1826dupA murine model recapitulates hypertrophic cardiomyopathy and skeletal muscle weakness of human IOPD, indicating its utility for evaluation of novel therapeutics.
Transcriptomic differences in MSA clinical variants
Authors: Pérez-Soriano Alexandra , Arnal Segura Magdalena , Botta-Orfila Teresa , Giraldo Darly , Fernández Manel , Compta Yaroslau , Fernández-Santiago Rubén , Ezquerra Mario , Tartaglia Gian G. , Martí M. J. ,   the Catalan MSA Registry (CMSAR), Muñoz Esteban , Pagonabarraga Javier , Valldeoriola Francesc , Hernández-Vara Jorge , Classen Serge Jauma , Puente Victor , Pont Claustre , Caballol Núria , de Fàbregues Oriol , Ávila Asunción , Calopa Matilde , Gaig Carles , Pastor Pau , Pujol Montserrat , Santamaria Joan , Planellás Lluís , Cámara Ana 
Published: June 2020

AbstractBackground: Multiple system atrophy (MSA) is a rare oligodendroglial synucleinopathy of unknown etiopathogenesis including two major clinical variants with predominant parkinsonism (MSA-P) or cerebellar dysfunction (MSA-C). Objective: To identify novel disease mechanisms we performed a blood transcriptomic study investigating differential gene expression changes and biological process alterations in MSA and its clinical subtypes. Methods: We compared the transcriptome from rigorously gender and age-balanced groups of 10 probable MSA-P, 10 probable MSA-C cases, 10 controls from the Catalan MSA Registry (CMSAR), and 10 Parkinson Disease (PD) patients. Results: Gene set enrichment analyses showed prominent positive enrichment in processes related to immunity and inflammation in all groups, and a negative enrichment in cell differentiation and development of the nervous system in both MSA-P and PD, in contrast to protein translation and processing in MSA-C. Gene set enrichment analysis using expression patterns in different brain regions as a reference also showed distinct results between the different synucleinopathies. Conclusions: In line with the two major phenotypes described in the clinic, our data suggest that gene expression and biological processes might be differentially affected in MSA-P and MSA-C. Future studies using larger sample sizes are warranted to confirm these results.
A new family of diprotodontian marsupials from the latest Oligocene of Australia and the evolution of wombats, koalas, and their relatives (Vombatiformes)
Authors: Beck Robin M. D. , Louys Julien , Brewer Philippa , Archer Michael , Black Karen H. , Tedford Richard H. 
Published: June 2020

AbstractWe describe the partial cranium and skeleton of a new diprotodontian marsupial from the late Oligocene (~26–25 Ma) Namba Formation of South Australia. This is one of the oldest Australian marsupial fossils known from an associated skeleton and it reveals previously unsuspected morphological diversity within Vombatiformes, the clade that includes wombats (Vombatidae), koalas (Phascolarctidae) and several extinct families. Several aspects of the skull and teeth of the new taxon, which we refer to a new family, are intermediate between members of the fossil family Wynyardiidae and wombats. Its postcranial skeleton exhibits features associated with scratch-digging, but it is unlikely to have been a true burrower. Body mass estimates based on postcranial dimensions range between 143 and 171 kg, suggesting that it was ~5 times larger than living wombats. Phylogenetic analysis based on 79 craniodental and 20 postcranial characters places the new taxon as sister to vombatids, with which it forms the superfamily Vombatoidea as defined here. It suggests that the highly derived vombatids evolved from wynyardiid-like ancestors, and that scratch-digging adaptations evolved in vombatoids prior to the appearance of the ever-growing (hypselodont) molars that are a characteristic feature of all post-Miocene vombatids. Ancestral state reconstructions on our preferred phylogeny suggest that bunolophodont molars are plesiomorphic for vombatiforms, with full lophodonty (characteristic of diprotodontoids) evolving from a selenodont morphology that was retained by phascolarctids and ilariids, and wynyardiids and vombatoids retaining an intermediate selenolophodont condition. There appear to have been at least six independent acquisitions of very large (>100 kg) body size within Vombatiformes, several having already occurred by the late Oligocene.
Risk of Ischemic Heart Disease and Stroke in Prostate Cancer Survivors: A Nationwide Study in South Korea
Authors: Shin Dong Wook , Han Kyungdo , Park Hyun Sik , Lee Seung-Pyo , Park Sang Hyun , Park Jinsung 
Published: June 2020

AbstractIn this study using national health insurance data, we investigated the risk of ischemic heart disease (IHD) and stroke among prostate cancer (PC) survivors compared with the general population, as well as the risk of cardiovascular disease (CVD) according to primary treatment. A total of 48,298 PC patients diagnosed from 2007 to 2013 were included and matched to non-cancer controls. Compared to the general population, PC survivors had a slightly lower risk of IHD (adjusted hazard ratio [aHR] = 0.89, 95% confidence interval [CI] 0.83–0.96) or stroke (aHR 0.90, 95% CI 0.87–0.95). Especially, survivors who underwent surgery had lower risks of IHD (aHR 0.70, 95% CI 0.61–0.80) or stroke (aHR 0.73, 95% CI 0.67–0.81). Compared to survivors in the active surveillance/watchful waiting group, the androgen deprivation therapy (ADT) group had a significantly greater risk of stroke (aHR 1.16, 95% CI 1.02–1.32), but the IHD risk was not significantly elevated (aHR 1.06, 95% CI 0.88–1.29). In conclusion, PC survivors had a slightly lower risk of CVD compared to the general population, which was attributable to self-selection for PSA screening, specifically in the surgery-only group. CVD risk was dependent on treatment received, and attention should be given to patients who receive ADT.
Validation of reference genes for the normalization of RT-qPCR gene expression in Acanthamoeba spp.
Authors: Köhsler Martina , Leitsch David , Müller Norbert , Walochnik Julia 
Published: June 2020

AbstractAcanthamoebae are potentially pathogenic organisms, with a highly unique, yet still insufficiently investigated metabolism. Many open questions can be addressed by gene expression studies, however, for Acanthamoeba reliable standards have not yet been established. In this study, suitable reference genes (RGs) for RT-qPCR in Acanthamoeba were comprehensively evaluated, comparing different Acanthamoeba strains and employing four different algorithms (NormFinder, GeNorm, BestKeeper and RefFinder). Expression stability was assessed under various conditions and the potentials of the most promising RGs for accurate normalization of target genes were evaluated. Expression stability of RGs varied depending on conditions and employed algorithms, however, the genes for the 18S rRNA and the hypoxanthine phosphoribosyl transferase seem to be widely suitable RGs. Normalization with a combination of two carefully chosen RGs resulted in reliable expression data for target genes, while normalization with unsuitable RGs led to significant misinterpretation of expression profiles. Thus, a careful evaluation of RGs prior to expression studies is essential.
Mechanisms of action of antimicrobial peptides ToAP2 and NDBP-5.7 against Candida albicans planktonic and biofilm cells
Authors: do Nascimento Dias Jhones , de Souza Silva Calliandra , de Araújo Alyne Rodrigues , Souza Jessica Maria Teles , de Holanda Veloso Júnior Paulo Henrique , Cabral Wanessa Felix , da Glória da Silva Maria , Eaton Peter , de Souza de Almeida Leite José Roberto , Nicola André Moraes , Albuquerque Patrícia , Silva-Pereira Ildinete 
Published: June 2020

AbstractCandida albicans is a major cause of human infections, ranging from relatively simple to treat skin and mucosal diseases to systemic life-threatening invasive candidiasis. Fungal infections treatment faces three major challenges: the limited number of therapeutic options, the toxicity of the available drugs, and the rise of antifungal resistance. In this study, we demonstrate the antifungal activity and mechanism of action of peptides ToAP2 and NDBP-5.7 against planktonic cells and biofilms of C. albicans. Both peptides were active against C. albicans cells; however, ToAP2 was more active and produced more pronounced effects on fungal cells. Both peptides affected C. albicans membrane permeability and produced changes in fungal cell morphology, such as deformations in the cell wall and disruption of ultracellular organization. Both peptides showed synergism with amphotericin B, while ToAP2 also presents a synergic effect with fluconazole. Besides, ToAP2 (6.25 µM.) was able to inhibit filamentation after 24 h of treatment and was active against both the early phase and mature biofilms of C. albicans. Finally, ToAP2 was protective in a Galleria mellonella model of infection. Altogether these results point to the therapeutic potential of ToAP2 and other antimicrobial peptides in the development of new therapies for C. albicans infections.
A novel intramuscular Interstitial Cell of Cajal is a candidate for generating pacemaker activity in the mouse internal anal sphincter
Authors: Hannigan Karen I. , Bossey Aaron P. , Foulkes Holly J. L. , Drumm Bernard T. , Baker Salah A. , Ward Sean M. , Sanders Kenton M. , Keef Kathleen D. , Cobine Caroline A. 
Published: June 2020

AbstractThe internal anal sphincter (IAS) generates phasic contractions and tone. Slow waves (SWs) produced by interstitial cells of Cajal (ICC) underlie phasic contractions in other gastrointestinal regions. SWs are also present in the IAS where only intramuscular ICC (ICC-IM) are found, however the evidence linking ICC-IM to SWs is limited. This study examined the possible relationship between ICC-IM and SWs by recording Ca2+transients in mice expressing a genetically-encoded Ca2+-indicator in ICC (Kit-Cre-GCaMP6f). A role for L-type Ca2+channels (CavL) and anoctamin 1 (ANO1) was tested since each is essential for SW and tone generation. Two distinct ICC-IM populations were identified. Type I cells (36% of total) displayed localised asynchronous Ca2+transients not dependent on CavLor ANO1; properties typical of ICC-IM mediating neural responses in other gastrointestinal regions. A second novel sub-type, i.e., Type II cells (64% of total) generated rhythmic, global Ca2+transients at the SW frequency that were synchronised with neighbouring Type II cells and were abolished following blockade of either CavLor ANO1. Thus, the spatiotemporal characteristics of Type II cells and their dependence upon CavLand ANO1 all suggest that these cells are viable candidates for the generation of SWs and tone in the IAS.
Long-term imaging of the photosensitive, reef-building coral Acropora muricata using light-sheet illumination
Authors: Laissue Pierre Philippe , Roberson Loretta , Gu Yan , Qian Chen , Smith David J. 
Published: June 2020

AbstractCoral reefs are in alarming decline due to climate emergency, pollution and other man-made disturbances. The numerous ecosystem services derived from coral reefs are underpinned by the growth and physical complexity of reef-forming corals. Our knowledge of their fundamental biology is limited by available technology. We need a better understanding of larval settlement and development, skeletogenesis, interactions with pathogens and symbionts, and how this biology interacts with environmental factors such as light exposure, temperature, and ocean acidification. We here focus on a fast-growing key coloniser, Acropora muricata (Linnaeus, 1758). To enable dynamic imaging of this photosensitive organism at different scales, we developed light-sheet illumination for fluorescence microscopy of small coral colonies. Our approach reveals live polyps in previously unseen detail. An imaging range for Acropora muricata with no measurable photodamage is defined based upon polyp expansion, coral tissue reaction, and photobleaching. We quantify polyp retraction as a photosensitive behavioural response and show coral tissue rupture at higher irradiance with blue light. The simple and flexible technique enables non-invasive continuous dynamic imaging of highly photosensitive organisms with sizes between 1 mm3 and 5 cm3, for eight hours, at high temporal resolution, on a scale from multiple polyps down to cellular resolution. This live imaging tool opens a new window into the dynamics of reef-building corals.
Superior Mechanical Performance of Inductively Sintered Al/SiC Nanocomposites Processed by Novel Milling Route
Authors: Almotairy Saud M. , Alharthi Nabeel H. , Alharbi Hamad F. , Abdo Hany S. 
Published: June 2020

AbstractThis paper explores new routes for flake powder metallurgy, with the aim of designing an effective route for fabricating metal matrix nanocomposites, combining high strength and good ductility. A new route that uses three speeds, instead of the two speeds characterizing the shift-speed ball milling (SSBM) route, has been suggested and implemented. The mechanisms of these routes were illustrated based on the intensity of ball-powder-ball collisions and the morphology evolution. The ball milled powder were characterized using filed emission scanning electron microscope (FESEM), X-ray diffractometer (XRD) and Energy dispersive spectroscopy (EDS) to investigate the morphology evolution of the composites powder and the homogenous distribution of the SiC nanoparticles within the Al matrix. The reinforcing adequacy and interfacial bonding of 2 wt.% SiC nanoparticles in an inductively sintered composite has been investigated. Mechanical testing of the produced bulk composites resulted in achieving superior mechanical properties, characterized by 92% higher hardness, 180% higher yield strength, 101% higher ultimate strength, and 0% loss in uniform elongation, compared with those of regular SSBM. This is attributed to the homogeneous dispersion of the reinforcement into the Al matrix.
Analyzing trend and forecasting of rainfall changes in India using non-parametrical and machine learning approaches
Authors: Praveen Bushra , Talukdar Swapan , Shahfahad  , Mahato Susanta , Mondal Jayanta , Sharma Pritee , Islam Abu Reza Md. Towfiqul , Rahman Atiqur 
Published: June 2020

AbstractThis study analyzes and forecasts the long-term Spatio-temporal changes in rainfall using the data from 1901 to 2015 across India at meteorological divisional level. The Pettitt test was employed to detect the abrupt change point in time frame, while the Mann-Kendall (MK) test and Sen’s Innovative trend analysis were performed to analyze the rainfall trend. The Artificial Neural Network-Multilayer Perceptron (ANN-MLP) was employed to forecast the upcoming 15 years rainfall across India. We mapped the rainfall trend pattern for whole country by using the geo-statistical technique like Kriging in ArcGIS environment. Results show that the most of the meteorological divisions exhibited significant negative trend of rainfall in annual and seasonal scales, except seven divisions during. Out of 17 divisions, 11 divisions recorded noteworthy rainfall declining trend for the monsoon season at 0.05% significance level, while the insignificant negative trend of rainfall was detected for the winter and pre-monsoon seasons. Furthermore, the significant negative trend (−8.5) was recorded for overall annual rainfall. Based on the findings of change detection, the most probable year of change detection was occurred primarily after 1960 for most of the meteorological stations. The increasing rainfall trend had observed during the period 1901–1950, while a significant decline rainfall was detected after 1951. The rainfall forecast for upcoming 15 years for all the meteorological divisions’ also exhibit a significant decline in the rainfall. The results derived from ECMWF ERA5 reanalysis data exhibit that increasing/decreasing precipitation convective rate, elevated low cloud cover and inadequate vertically integrated moisture divergence might have influenced on change of rainfall in India. Findings of the study have some implications in water resources management considering the limited availability of water resources and increase in the future water demand.
Electrophysiological evidence of preserved hearing at the end of life
Authors: Blundon Elizabeth G. , Gallagher Romayne E. , Ward Lawrence M. 
Published: June 2020

AbstractThis study attempts to answer the question: “Is hearing the last to go?” We present evidence of hearing among unresponsive actively dying hospice patients. Individual ERP (MMN, P3a, and P3b) responses to deviations in auditory patterns are reported for conscious young, healthy control participants, as well as for hospice patients, both when the latter were conscious, and again when they became unresponsive to their environment. Whereas the MMN (and perhaps too the P3a) is considered an automatic response to auditory irregularities, the P3b is associated with conscious detection of oddball targets. All control participants, and most responsive hospice patients, evidenced a “local” effect (either a MMN, a P3a, or both) and some a “global” effect (P3b) to deviations in tone, or deviations in auditory pattern. Importantly, most unresponsive patients showed evidence of MMN responses to tone changes, and some showed a P3a or P3b response to either tone or pattern changes. Thus, their auditory systems were responding similarly to those of young, healthy controls just hours from end of life. Hearing may indeed be one of the last senses to lose function as humans die.