bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of oculomotor control during reading of mirrored and inverted texts
Authors: Chandra Johan , Krügel André , Engbert Ralf 
Published: March 2020

AbstractThe interplay between cognitive and oculomotor processes during reading can be explored when the spatial layout of text deviates from the typical display. In this study, we investigate various eye-movement measures during reading of text with experimentally manipulated layout (word-wise and letter-wise mirrored-reversed text as well as inverted and scrambled text). While typical findings (e.g., longer mean fixation times, shorter mean saccades lengths) in reading manipulated texts compared to normal texts were reported in earlier work, little is known about changes of oculomotor targeting observed in within-word landing positions under the above text layouts. Here we carry out precise analyses of landing positions and find substantial changes in the so-called launch-site effect in addition to the expected overall slow-down of reading performance. Specifically, during reading of our manipulated text conditions with reversed letter order (against overall reading direction), we find a reduced launch-site effect, while in all other manipulated text conditions, we observe an increased launch-site effect. Our results clearly indicate that the oculomotor system is highly adaptive when confronted with unusual reading conditions.
Evidence of Cosmic Impact at Abu Hureyra, Syria at the Younger Dryas Onset (~12.8 ka): High-temperature melting at >2200 °C
Authors: Moore Andrew M. T. , Kennett James P. , Napier William M. , Bunch Ted E. , Weaver James C. , LeCompte Malcolm , Adedeji A. Victor , Hackley Paul , Kletetschka Gunther , Hermes Robert E. , Wittke James H. , Razink Joshua J. , Gaultois Michael W. , West Allen 
Published: March 2020

AbstractAt Abu Hureyra (AH), Syria, the 12,800-year-old Younger Dryas boundary layer (YDB) contains peak abundances in meltglass, nanodiamonds, microspherules, and charcoal. AH meltglass comprises 1.6 wt.% of bulk sediment, and crossed polarizers indicate that the meltglass is isotropic. High YDB concentrations of iridium, platinum, nickel, and cobalt suggest mixing of melted local sediment with small quantities of meteoritic material. Approximately 40% of AH glass display carbon-infused, siliceous plant imprints that laboratory experiments show formed at a minimum of 1200°–1300 °C; however, reflectance-inferred temperatures for the encapsulated carbon were lower by up to 1000 °C. Alternately, melted grains of quartz, chromferide, and magnetite in AH glass suggest exposure to minimum temperatures of 1720 °C ranging to >2200 °C. This argues against formation of AH meltglass in thatched hut fires at 1100°–1200 °C, and low values of remanent magnetism indicate the meltglass was not created by lightning. Low meltglass water content (0.02–0.05% H2O) is consistent with a formation process similar to that of tektites and inconsistent with volcanism and anthropogenesis. The wide range of evidence supports the hypothesis that a cosmic event occurred at Abu Hureyra ~12,800 years ago, coeval with impacts that deposited high-temperature meltglass, melted microspherules, and/or platinum at other YDB sites on four continents.
Comparative analysis of HER2 copy number between plasma and tissue samples in gastric cancer using droplet digital PCR
Authors: Kim Boram , Nam Soo Kyung , Seo Soo Hyun , Park Kyoung Un , Ahn Sang-Hoon , Park Do Joong , Kim Hyung-Ho , Kim Woo Ho , Lee Hye Seung 
Published: March 2020

AbstractIn this study, we measured the human epidermal growth factor receptor 2 (HER2) copy number in both tissue and plasma samples of gastric cancer patients by using droplet digital polymerase chain reaction (ddPCR) method. Eighty gastric cancer patients were enrolled and both formalin-fixed and paraffin-embedded tissue and preoperative plasma samples were collected. HER2 status was determined by HER2 immunohistochemistry (IHC)/silver in situ hybridization (SISH) in tissue samples and ddPCR of the target gene HER2 and the reference gene eukaryotic translation initiation factor 2C, 1 in both tissue and plasma. The concordance rate of tissue HER2 status determined by IHC/SISH and HER2 ddPCR was 90.0% (72/80), and the sensitivity and specificity of tissue ddPCR were 85.0% and 95.0%, respectively. The concordance rate of plasma ddPCR and IHC/SISH was 63.8% (51/80). The sensitivity, specificity, positive predictive value, and negative predictive value of plasma HER2 ddPCR were 37.5%, 90.0%, 79.0%, and 59.0%, respectively. As HER2 measurement by tissue ddPCR showed a high concordance rate with HER2 status by IHC/SISH, it could replace tissue IHC/SISH testing in gastric cancer. These findings may contribute to the development of tissue and plasma HER2 testing that would be useful in daily practice.
Pancreatic islets seeded in a novel bioscaffold forms an organoid to rescue insulin production and reverse hyperglycemia in models of type 1 diabetes
Authors: Elizondo Diana M. , Brandy Nailah Z. D. , da Silva Ricardo L. L. , de Moura Tatiana R. , Ali Jamel , Yang Dazhi , Lipscomb Michael W. 
Published: March 2020

AbstractTherapeutic approaches to combat type 1 diabetes (T1D) include donor pancreas transplantation, exogenous insulin administration and immunosuppressive therapies. However, these clinical applications are limited due to insufficient tissue compatible donors, side effects of exogenous insulin administration and/or increased onset of opportunistic infections attributable to induced global immunosuppression. An alternative approach to alleviate disease states is to utilize insulin-producing pancreatic islets seeded in a bioscaffold for implantation into diabetic recipients. The present studies now report that a newly developed cationic polymer biomaterial serves as an efficient bioscaffold for delivery of donor syngeneic pancreatic islet cells to reverse hyperglycemia in murine streptozotocin induced- or non-obese diabetic mouse models of T1D. Intraperitoneal implantation of pancreatic islets seeded within the copolymer bioscaffold supports long-term cell viability, response to extracellular signaling cues and ability to produce soluble factors into the microenvironment. Elevated insulin levels were measured in recipient diabetic mice upon implantation of the islet-seeded biomaterial coupled with reduced blood glucose levels, collectively resulting in increased survival and stabilization of metabolic indices. Importantly, the implanted islet-seeded biomaterial assembled into a solid organoid substructure that reorganized the extracellular matrix compartment and recruited endothelial progenitors for neovascularization. This allowed survival of the graft long-termin vivoand access to the blood for monitoring glucose levels. These results highlight the novelty, simplicity and effectiveness of this biomaterial for tissue regeneration andin vivorestoration of organ functions.
Transcriptomic and computational analysis identified LPA metabolism, KLHL14 and KCNE3 as novel regulators of Epithelial-Mesenchymal Transition
Authors: Di Lollo V. , Canciello A. , Orsini M. , Bernabò N. , Ancora M. , Di Federico M. , Curini V. , Mattioli M. , Russo V. , Mauro A. , Cammà C. , Barboni B. 
Published: March 2020

AbstractEpithelial-mesenchymal transition (EMT) is a complex biological program between physiology and pathology. Here, amniotic epithelial cells (AEC) were used as in vitro model of transiently inducible EMT in order to evaluate the transcriptional insights underlying this process. Therefore, RNA-seq was used to identify the differentially expressed genes and enrichment analyses were carried out to assess the intracellular pathways involved. As a result, molecules exclusively expressed in AEC that experienced EMT (GSTA1-1 and GSTM3) or when this process is inhibited (KLHL14 and KCNE3) were identified. Lastly, the network theory was used to obtain a computational model able to recognize putative controller genes involved in the induction and in the prevention of EMT. The results suggested an opposite role of lysophosphatidic acid (LPA) synthesis and degradation enzymes in the regulation of EMT process. In conclusion, these molecules may represent novel EMT regulators and also targets for developing new therapeutic strategies.
Transcriptomic and metabolomic analyses of Lycium ruthenicum and Lycium barbarum fruits during ripening
Authors: Zhao Jianhua , Li Haoxia , Yin Yue , An Wei , Qin Xiaoya , Wang Yajun , Li Yanlong , Fan Yunfang , Cao Youlong 
Published: March 2020

AbstractRed wolfberry (or goji berry,Lycium barbarum; LB) is an important agricultural product with a high content of pharmacologically important secondary metabolites such as phenylpropanoids. A close relative, black wolfberry (L. ruthenicum; LR), endemic to the salinized deserts of northwestern China, is used only locally. The two fruits exhibit many morphological and phytochemical differences, but genetic mechanisms underlying them remain poorly explored. In order to identify the genes of interest for further studies, we studied transcriptomic (Illumina HiSeq) and metabolomic (LC-MS) profiles of the two fruits during five developmental stages (young to ripe). As expected, we identified much higher numbers of significantly differentially regulated genes (DEGs) than metabolites. The highest numbers were identified in pairwise comparisons including the first stage for both species, but total numbers were consistently somewhat lower for the LR. The number of differentially regulated metabolites in pairwise comparisons of developmental stages varied from 66 (stages 3 vs 4) to 133 (stages 2 vs 5) in both species. We identified a number of genes (e.g.AAT1,metE,pip) and metabolites (e.g. rutin, raffinose, galactinol, trehalose, citrulline and DL-arginine) that may be of interest to future functional studies of stress adaptation in plants. As LB is also highly suitable for combating soil desertification and alleviating soil salinity/alkalinity/pollution, its potential for human use may be much wider than its current, highly localized, relevance.
Selective Binding of HSC70 and its Co-Chaperones to Structural Hotspots on CFTR
Authors: Baaklini Imad , Gonçalves Conrado de Campos , Lukacs Gergely L. , Young Jason C. 
Published: March 2020

AbstractMutations in the cystic fibrosis transmembrane conductance regulator (CFTR) channel cause cystic fibrosis. Chaperones, including HSC70, DNAJA1 and DNAJA2, play key roles in both the folding and degradation of wild-type and mutant CFTR at multiple cellular locations. DNAJA1 and HSC70 promote the folding of newly synthesized CFTR at the endoplasmic reticulum (ER), but are required for the rapid turnover of misfolded channel at the plasma membrane (PM). DNAJA2 and HSC70 are also involved in the ER-associated degradation (ERAD) of misfolded CFTR, while they assist the refolding of destabilized channel at the PM. These outcomes may depend on the binding of chaperones to specific sites within CFTR, which would be exposed in non-native states. A CFTR peptide library was used to identify binding sites for HSC70, DNAJA1 and DNAJA2, validated by competition and functional assays. Each chaperone had a distinct binding pattern, and sites were distributed between the surfaces of the CFTR cytosolic domains, and domain interfaces known to be important for channel assembly. The accessibility of sites to chaperones will depend on the degree of CFTR folding or unfolding. Different folded states may be recognized by unique combinations of HSC70, DNAJA1 and DNAJA2, leading to divergent biological effects.
A Novel System for Functional Determination of Variants of Uncertain Significance using Deep Convolutional Neural Networks
Authors: Zimmerman Lior , Zelichov Ori , Aizenmann Arie , Barbash Zohar , Vidne Michael , Tarcic Gabi 
Published: March 2020

AbstractMany drugs are developed for commonly occurring, well studied cancer drivers such as vemurafenib for BRAF V600E and erlotinib for EGFR exon 19 mutations. However, most tumors also harbor mutations which have an uncertain role in disease formation, commonly called Variants of Uncertain Significance (VUS), which are not studied or characterized and could play a significant role in drug resistance and relapse. Therefore, the determination of the functional significance of VUS and their response to Molecularly Targeted Agents (MTA) is essential for developing new drugs and predicting response of patients. Here we present a multi-scale deep convolutional neural network (DCNN) architecture combined with an in-vitro functional assay to investigate the functional role of VUS and their response to MTA’s. Our method achieved high accuracy and precision on a hold-out set of examples (0.98 mean AUC for all tested genes) and was used to predict the oncogenicity of 195 VUS in 6 genes. 63 (32%) of the assayed VUS’s were classified as pathway activating, many of them to a similar extent as known driver mutations. Finally, we show that responses of various mutations to FDA approved MTAs are accurately predicted by our platform in a dose dependent manner. Taken together this novel system can uncover the treatable mutational landscape of a drug and be a useful tool in drug development.
Gene-flow from steppe individuals into Cucuteni-Trypillia associated populations indicates long-standing contacts and gradual admixture
Authors: Immel Alexander , Țerna Stanislav , Simalcsik Angela , Susat Julian , Šarov Oleg , Sîrbu Ghenadie , Hofmann Robert , Müller Johannes , Nebel Almut , Krause-Kyora Ben 
Published: March 2020

AbstractThe Cucuteni-Trypillia complex (CTC) flourished in eastern Europe for over two millennia (5100–2800 BCE) from the end of the Neolithic to the Early Bronze Age. Its vast distribution area encompassed modern-day eastern Romania, Moldova and western/central Ukraine. Due to a lack of existing burials throughout most of this time, only little is known about the people associated with this complex and their genetic composition. Here, we present genome-wide data generated from the skeletal remains of four females that were excavated from two Late CTC sites in Moldova (3500–3100 BCE). All individuals carried a large Neolithic-derived ancestry component and were genetically more closely related to Linear Pottery than to Anatolian farmers. Three of the specimens also showed considerable amounts of steppe-related ancestry, suggesting influx into the CTC gene-pool from people affiliated with, for instance, the Ukraine Mesolithic. The latter scenario is supported by archaeological evidence. Taken together, our results confirm that the steppe component arrived in eastern Europe farming communities maybe as early as 3500 BCE. In addition, they are in agreement with the hypothesis of ongoing contacts and gradual admixture between incoming steppe and local western populations.
Diet influences the functions of the human intestinal microbiome
Authors: De Angelis Maria , Ferrocino Ilario , Calabrese Francesco Maria , De Filippis Francesca , Cavallo Noemi , Siragusa Sonya , Rampelli Simone , Di Cagno Raffaella , Rantsiou Kalliopi , Vannini Lucia , Pellegrini Nicoletta , Lazzi Camilla , Turroni Silvia , Lorusso Nicola , Ventura Mario , Chieppa Marcello , Neviani Erasmo , Brigidi Patrizia , O’Toole Paul W. , Ercolini Danilo , Gobbetti Marco , Cocolin Luca 
Published: March 2020

AbstractGut microbes programme their metabolism to suit intestinal conditions and convert dietary components into a panel of small molecules that ultimately affect host physiology. To unveil what is behind the effects of key dietary components on microbial functions and the way they modulate host–microbe interaction, we used for the first time a multi-omic approach that goes behind the mere gut phylogenetic composition and provides an overall picture of the functional repertoire in 27 fecal samples from omnivorous, vegan and vegetarian volunteers. Based on our data, vegan and vegetarian diets were associated to the highest abundance of microbial genes/proteins responsible for cell motility, carbohydrate- and protein-hydrolyzing enzymes, transport systems and the synthesis of essential amino acids and vitamins. A positive correlation was observed when intake of fiber and the relative fecal abundance of flagellin were compared. Microbial cells and flagellin extracted from fecal samples of 61 healthy donors modulated the viability of the human (HT29) colon carcinoma cells and the host response through the stimulation of the expression of Toll-like receptor 5, lectin RegIIIα and three interleukins (IL-8, IL-22 and IL-23). Our findings concretize a further and relevant milestone on how the diet may prevent/mitigate disease risk.
Socio-ecological connectivity differs in magnitude and direction across urban landscapes
Authors: Egerer Monika , Fouch Nakisha , Anderson Elsa C. , Clarke Mysha 
Published: March 2020

AbstractConnectivity of social-ecological systems promotes resilience across urban landscapes. Community gardens are social-ecological systems that support food production, social interactions, and biodiversity conservation. We investigate how these hubs of ecosystem services facilitate socio-ecological connectivity and service flows as a network across complex urban landscapes. In three US cities (Baltimore, Chicago, New York City), we use community garden networks as a model system to demonstrate how biophysical and social features of urban landscapes control the pattern and magnitude of ecosystem service flows through these systems. We show that community gardens within a city are connected through biological and social mechanisms, and connectivity levels and spatial arrangement differ across cities. We found that biophysical connectivity was higher than social connectivity in one case study, while they were nearly equal in the other two. This higher social connectivity can be attributed to clustered distributions of gardens within neighborhoods (network modularity), which promotes neighborhood-scale connectivity hotspots, but produces landscape-scale connectivity coldspots. The particular patterns illustrate how urban form and social amenities largely shape ecosystem service flows among garden networks. Such socio-ecological analyses can be applied to enhance and stabilize landscape connectedness to improve life and resilience in cities.
Rapid Pyrazinamide Drug Susceptibility Testing using a Closed-Tube PCR Assay of the Entire pncA gene
Authors: Whitfield Michael G. , Marras Salvatore A. E. , Warren Rob M. , Van Rie Annelies , Rice John , Wangh Lawrence J. , Kreiswirth Barry N. 
Published: March 2020

AbstractThe continued use of pyrazinamide in the treatment of tuberculosis in the absence of a rapid, accurate and standardized pyrazinamide drug susceptibility assays is of great concern. While whole genome sequencing holds promise, it is not yet feasible option in low resource settings as it requires expensive instruments and bioinformatic analysis. We investigated the diagnostic performance of a closed-tube Linear-After-The-Exponential (LATE)-PCR assay for pyrazinamide susceptibility in Mycobacterium tuberculosis. Based on a set of 654 clinical Mycobacterium tuberculosis culture isolates with known mutations throughout the pncA gene as determined by Sanger sequencing, the assay displays excellent sensitivity of 96.9% (95% CI: 95.2–98.6) and specificity of 97.9% (95% CI: 96.1–99.7). In a subset of 384 isolates with phenotypic drug susceptibility testing, we also observed high sensitivity of 98.9% (95% CI: 97.5–100) but lower specificity of 91.8% (95% CI: 87.9–95.8) when compared to phenotypic drug susceptibility testing. We conclude that the LATE PCR assay offers both a rapid and accurate prediction of pyrazinamide susceptibility.
RESTORE: Robust intEnSiTy nORmalization mEthod for multiplexed imaging
Authors: Chang Young Hwan , Chin Koei , Thibault Guillaume , Eng Jennifer , Burlingame Erik , Gray Joe W. 
Published: March 2020

AbstractRecent advances in multiplexed imaging technologies promise to improve the understanding of the functional states of individual cells and the interactions between the cells in tissues. This often requires compilation of results from multiple samples. However, quantitative integration of information between samples is complicated by variations in staining intensity and background fluorescence that obscure biological variations. Failure to remove these unwanted artifacts will complicate downstream analysis and diminish the value of multiplexed imaging for clinical applications. Here, to compensate for unwanted variations, we automatically identify negative control cells for each marker within the same tissue and use their expression levels to infer background signal level. The intensity profile is normalized by the inferred level of the negative control cells to remove between-sample variation. Using a tissue microarray data and a pair of longitudinal biopsy samples, we demonstrated that the proposed approach can remove unwanted variations effectively and shows robust performance.
Pathway-specific enzymes from bamboo and crop leaves biosynthesize anti-nociceptive C-glycosylated flavones
Authors: Sun Yuwei , Chen Zhuo , Yang Jingya , Mutanda Ishmael , Li Shiyi , Zhang Qian , Zhang Ying , Zhang Yulian , Wang Yong 
Published: March 2020

AbstractC-glycosylated flavones (CGFs) are promising candidates as anti-nociceptive compounds. The leaves of bamboo and related crops in the grass family are a largely unexploited bioresource with a wide array of CGFs. We report here pathway-specific enzymes includingC-glycosyltransferases (CGTs) and P450 hydroxylases from cereal crops and bamboo species accumulating abundant CGFs. Mining of CGTs and engineering of P450s that decorate the flavonoid skeleton allowed the production of desired CGFs (with yield of 20–40 mg/L) in anEscherichia colicell factory. We further explored the antinociceptive activity of major CGFs in mice models and identified isoorientin as the most potent, with both neuroanalgesic and anti-inflammatory effects superior to clinical drugs such as rotundine and aspirin. Our discovery of the pain-alleviating flavonoids elicited from bamboo and crop leaves establishes this previously underutilized source, and sheds light on the pathway and pharmacological mechanisms of the compounds.
Growth and rapid succession of methanotrophs effectively limit methane release during lake overturn
Authors: Mayr Magdalena J. , Zimmermann Matthias , Dey Jason , Brand Andreas , Wehrli Bernhard , Bürgmann Helmut 
Published: March 2020

AbstractLakes and reservoirs contribute substantially to atmospheric concentrations of the potent greenhouse gas methane. Lake sediments produce large amounts of methane, which accumulate in the oxygen-depleted bottom waters of stratified lakes. Climate change and eutrophication may increase the number of lakes with methane storage in the future. Whether stored methane escapes to the atmosphere during annual lake overturn is a matter of controversy and depends critically on the response of the methanotroph assemblage. Here we show, by combining 16S rRNA gene and pmoA mRNA amplicon sequencing, qPCR, CARD-FISH and potential methane-oxidation rate measurements, that the methanotroph assemblage in a mixing lake underwent both a substantial bloom and ecological succession. As a result, methane oxidation kept pace with the methane supplied from methane-rich bottom water and most methane was oxidized. This aspect of freshwater methanotroph ecology represents an effective mechanism limiting methane transfer from lakes to the atmosphere.