bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic diversity, linkage disequilibrium and selection signatures in European local pig breeds assessed with a high density SNP chip
Authors: Muñoz M. , Bozzi R. , García-Casco J. , Núñez Y. , Ribani A. , Franci O. , García F. , Škrlep M. , Schiavo G. , Bovo S. , Utzeri V. J. , Charneca R. , Martins J. M. , Quintanilla R. , Tibau J. , Margeta V. , Djurkin-Kušec I. , Mercat M. J. , Riquet J. , Estellé J. , Zimmer C. , Razmaite V. , Araujo J. P. , Radović Č. , Savić R. , Karolyi D. , Gallo M. , Čandek-Potokar M. , Fernández A. I. , Fontanesi L. , Óvilo C. 
Published: September 2019

AbstractGenetic characterization of local breeds is essential to preserve their genomic variability, to advance conservation policies and to contribute to their promotion and sustainability. Genomic diversity of twenty European local pig breeds and a small sample of Spanish wild pigs was assessed using high density SNP chips. A total of 992 DNA samples were analyzed with the GeneSeek Genomic Profiler (GGP) 70 K HD porcine genotyping chip. Genotype data was employed to compute genetic diversity, population differentiation and structure, genetic distances, linkage disequilibrium and effective population size. Our results point out several breeds, such as Turopolje, Apulo Calabrese, Casertana, Mora Romagnola and Lithuanian indigenous wattle, having the lowest genetic diversity, supported by low heterozygosity and very small effective population size, demonstrating the need of enhanced conservation strategies. Principal components analysis showed the clustering of the individuals of the same breed, with few breeds being clearly isolated from the rest. Several breeds were partially overlapped, suggesting genetic closeness, which was particularly marked in the case of Iberian and Alentejana breeds. Spanish wild boar was also narrowly related to other western populations, in agreement with recurrent admixture between wild and domestic animals. We also searched across the genome for loci under diversifying selection based on FSToutlier tests. Candidate genes that may underlie differences in adaptation to specific environments and productive systems and phenotypic traits were detected in potentially selected genomic regions.
Atroposelective antibodies as a designed protein scaffold for artificial metalloenzymes
Authors: Adachi Takuma , Harada Akira , Yamaguchi Hiroyasu 
Published: September 2019

AbstractDesign and engineering of protein scaffolds are crucial to create artificial metalloenzymes. Herein we report the first example of C-C bond formation catalyzed by artificial metalloenzymes, which consist of monoclonal antibodies (mAbs) and C2 symmetric metal catalysts. Prepared as a tailored protein scaffold for a binaphthyl derivative (BN), mAbs bind metal catalysts bearing a 1,1′-bi-isoquinoline (BIQ) ligand to yield artificial metalloenzymes. These artificial metalloenzymes catalyze the Friedel-Crafts alkylation reaction. In the presence of mAb R44E1, the reaction proceeds with 88% ee. The reaction catalyzed by Cu-catalyst incorporated into the binding site of mAb R44E1 is found to show excellent enantioselectivity with 99% ee. The protein environment also enables the use of BIQ-based catalysts as asymmetric catalysts for the first time.
Targeted multiplex proteomics for molecular prescreening and biomarker discovery in metastatic colorectal cancer
Authors: Serna Garazi , Ruiz-Pace Fiorella , Cecchi Fabiola , Fasani Roberta , Jimenez Jose , Thyparambil Sheeno , Landolfi Stefania , Elez Elena , Vivancos Ana , Hembrough Todd , Tabernero Josep , Dienstmann Rodrigo , Nuciforo Paolo 
Published: September 2019

AbstractProtein biomarkers are widely used in cancer diagnosis, prognosis, and prediction of treatment response. Here we introduce the use of targeted multiplex proteomics (TMP) as a tool to simultaneously measure a panel of 54 proteins involved in oncogenic, tumour suppression, drug metabolism and resistance, in patients with metastatic colorectal cancer (mCRC). TMP provided valuable diagnostic information by unmasking an occult neuroendocrine differentiation and identifying a misclassified case based on abnormal proteins phenotype. No significant differences in protein levels between unpaired primary and metastatic samples were observed. Four proteins were found differentially expressed in KRAS-mutant as compared to wild-type tumours (overexpressed in mutant: KRAS, EGFR; overexpressed in wild-type: TOPO1, TOP2A). Survival analyses revealed the association between mesothelin expression and poor overall survival, whereas lack of PTEN protein expression associated with lower progression-free survival with anti-EGFR-based therapy in the first-line setting for patients with RAS wild-type tumour. Finally, outlier analysis identified putative targetable proteins in 65% of patients lacking a targetable genomic alteration. Our data show that TMP constitutes a promising, novel molecular prescreening tool in mCRC to identify protein expression alterations that may impact on patient outcomes and more precisely guide patient eligibility to clinical trials with novel targeted experimental therapies.
Analyzing expression and phosphorylation of the EGF receptor in HNSCC
Authors: Kriegs Malte , Clauditz Till Sebastian , Hoffer Konstantin , Bartels Joanna , Buhs Sophia , Gerull Helwe , Zech Henrike Barbara , Bußmann Lara , Struve Nina , Rieckmann Thorsten , Petersen Cordula , Betz Christian Stephan , Rothkamm Kai , Nollau Peter , Münscher Adrian 
Published: September 2019

AbstractOverexpression of the epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas (HNSCC) is considered to cause increased EGFR activity, which adds to tumorigenicity and therapy resistance. Since it is still unclear, whether EGFR expression is indeed associated with increased activity in HNSCC, we analyzed the relationship between EGFR expression and auto-phosphorylation as a surrogate marker for activity. We used a tissue micro array, fresh frozen HNSCC tumor and corresponding normal tissue samples and a large panel of HNSCC cell lines. While we observed substantial overexpression only in approximately 20% of HNSCC, we also observed strong discrepancies between EGFR protein expression and auto-phosphorylation in HNSCC cell lines as well as in tumor specimens using Western blot and SH2-profiling; for the majority of HNSCC EGFR expression therefore seems not to be correlated with EGFR auto-phosphorylation. Blocking of EGFR activity by cetuximab and erlotinib points to increased EGFR activity in samples with increased basal auto-phosphorylation. However, we could also identify cells with low basal phosphorylation but relevant EGFR activity. In summary, our data demonstrate that EGFR expression and activity are not well correlated. Therefore EGFR positivity is no reliable surrogate marker for EGFR activity, arguing the need for alternative biomarkers or functional predictive tests.
Structural Brain Correlates of Loneliness among Older Adults
Authors: Düzel Sandra , Drewelies Johanna , Gerstorf Denis , Demuth Ilja , Steinhagen-Thiessen Elisabeth , Lindenberger Ulman , Kühn Simone 
Published: September 2019

AbstractAmple evidence indicates that loneliness in old age is associated with poor bodily and mental health. However, little is known about structural cerebral correlates of loneliness in healthy older adults. We examined such correlates in a magnetic resonance imaging (MRI) subsample of 319 older adults aged 61 to 82 years drawn from the Berlin Aging Study II. Using voxel-based morphometry (VBM) and structural equation modeling (SEM), latent hierarchical regression analyses were performed to examine associations of (i) loneliness, (ii) a range of covariates, and (iii) loneliness by covariate interactions with latent brain volume estimates of brain structures known to be involved in processing, expressing, and regulating emotions. Results from whole-brain VBM analyses showed that individuals with higher loneliness scores tended to have smaller gray matter volumes in three clusters comprising (i) the left amygdala/anterior hippocampus, (ii) the left posterior parahippocampus and (iii) the left cerebellum. Significant associations and interactions between loneliness and latent factors for the amygdala and the hippocampus were confirmed with a region-of-interest (ROI)-based approach. These findings suggest that individual differences in loneliness among older adults are correlated with individual differences in the volumes of brain regions that are central to cognitive processing and emotional regulation, also after correcting for confounders such as social network size. We discuss possible mechanisms underlying these associations and their implications.
One Step Fabrication of Highly Absorptive and Surface Enhanced Raman Scattering (SERS) Silver Nano-trees on Silicon Substrate
Authors: Razek Sara Abdel , Ayoub Ahmed B. , Swillam Mohamed A. 
Published: September 2019

AbstractSilver Nano-trees (AgNTs) were synthesized by one-step electroless method with different densities via water or ethylene glycol (EG) on silicon substrate in one minute. The density of AgNTs is controlled by changing the concentration of silver nitrate in etchant solution. The absorption of NTs fabricated via EG is higher than absorption of NTs without EG. The AgNTs are employed as substrates for surface-enhanced Raman scattering (SERS) and exhibit high sensitivity. The silver Nano-trees fabricated via ethylene glycol (AgNTs-EG) enhances the Raman spectrum of pyridine (Py) with higher enhancement factor. Moreover, the SERS-active substrates prepared by using EG were able to detect Pyridine with concentration as low as 0.005 mM, the ones fabricated by water could only detect Pyridine at concentration of 0.2 mM.
IgA-deficient humans exhibit gut microbiota dysbiosis despite secretion of compensatory IgM
Authors: Catanzaro Jason R. , Strauss Juliet D. , Bielecka Agata , Porto Anthony F. , Lobo Francis M. , Urban Andrea , Schofield Whitman B. , Palm Noah W. 
Published: September 2019

AbstractImmunoglobulin A is the dominant antibody isotype found in mucosal secretions and enforces host-microbiota symbiosis in mice, yet selective IgA-deficiency (sIgAd) in humans is often described as asymptomatic. Here, we determined the effects of IgA deficiency on human gut microbiota composition and evaluated the possibility that mucosal secretion of IgM can compensate for a lack of secretory IgA. We used 16S rRNA gene sequencing and bacterial cell sorting to evaluate gut microbiota composition and taxa-specific antibody coating of the gut microbiota in 15 sIgAd subjects and matched controls. Despite the secretion of compensatory IgM into the gut lumen, sIgAd subjects displayed an altered gut microbiota composition as compared to healthy controls. These alterations were characterized by a trend towards decreased overall microbial diversity as well as significant shifts in the relative abundances of specific microbial taxa. While secretory IgA in healthy controls targeted a defined subset of the microbiota via high-level coating, compensatory IgM in sIgAd subjects showed less specificity than IgA and bound a broader subset of the microbiota. We conclude that IgA plays a critical and non-redundant role in controlling gut microbiota composition in humans and that secretory IgA has evolved to maintain a diverse and stable gut microbial community.
Resiliency of Mutualistic Supplier-Manufacturer Networks
Authors: Xu Mengkai , Radhakrishnan Srinivasan , Kamarthi Sagar , Jin Xiaoning 
Published: September 2019

AbstractCurrent Supplier-Manufacturer (SM) networks are highly complex and susceptible to local and global disruptions, due to connectivity and interdependency among suppliers and manufacturers. Resiliency of supply chains is critical for organizations to remain operational in the face of disruptive events. Existing quantitative analyses oversimplify the mutualistic nature of SM networks, in which failure of individual entities affects not only the directly connected entities but also those connected indirectly. In this work we investigate resiliency of SM networks using the quantitative methods employed to study mutualistic ecological systems. Much like in ecological systems, catastrophic failures of SM networks are difficult to predict due to high dimensionality of their interactive space. To address this, first we create a bipartite representation and generate a multidimensional nonlinear model that captures the dynamics of a SM network. We transform the multidimensional model into a two-dimensional model without sacrificing the model’s ability to predict the point of collapse. We extensively validate the model using real-world global automotive SM networks. We observe that the resiliency of a SM network depends on both the network structure and parameters. The current work offers a means for designing resilient supply chains that can remain robust to local and global perturbations.
Bulk superconductivity in a four-layer-type Bi-based compound La2O2Bi3Ag0.6Sn0.4S5.7Se0.3
Authors: Jha Rajveer , Goto Yosuke , Matsuda Tatsuma D. , Aoki Yuji , Nagao Masanori , Tanaka Isao , Mizuguchi Yoshikazu 
Published: September 2019

AbstractRecently, we reported the observation of superconductivity at ~0.5 K in a La2O2M4S6-type (M: metal) layered compound La2O2Bi3AgS6, which is a layered system related to the BiS2-based superconductor system but possesses a thicker Bi3AgS6-type conducting layer. In this study, we have developed the La2O2Bi3AgS6-type materials by element substitutions to increase the transition temperature (Tc) and to induce bulk nature of superconductivity. A resistivity anomaly observed at 180 K in La2O2Bi3AgS6 was systematically suppressed by Sn substitution for the Ag site. By the Sn substitution, Tc increased, and the shielding volume fraction estimated from magnetization measurements also increased. The highest Tc (=2.3 K) and the highest shielding volume fraction (~20%) was observed for La2O2Bi3Ag0.6Sn0.4S6. The superconducting properties were further improved by Se substitutions for the S site. By the combinational substitutions of Sn and Se, bulk-superconducting phase of La2O2Bi3Ag0.6Sn0.4S5.7Se0.3 with a Tc of 3.0 K (Tconset = 3.6 K) was obtained.
Prebiotic Phosphorylation of Uridine using Diamidophosphate in Aerosols
Authors: Castañeda A. D. , Li Z. , Joo T. , Benham K. , Burcar B. T. , Krishnamurthy R. , Liotta C. L. , Ng N. L. , Orlando T. M. 
Published: September 2019

AbstractOne of the most challenging fundamental problems in establishing prebiotically plausible routes for phosphorylation reactions using phosphate is that they are thermodynamically unfavorable in aqueous conditions. Diamidophosphate (DAP), a potentially prebiotically relevant compound, was shown to phosphorylate nucleosides in aqueous medium, albeit at a very slow rate (days/weeks). Here, we demonstrate that performing these reactions within an aerosol environment, a suitable model for the early Earth ocean-air interface, yields higher reaction rates when compared to bulk solution, thus overcoming these rate limitations. As a proof-of-concept, we demonstrate the effective conversion (~6.5–10%) of uridine to uridine-2′,3′-cyclophosphate in less than 1 h. These results suggest that aerosol environments are a possible scenario in which prebiotic phosphorylation could have occurred despite unfavorable rates in bulk solution.
The specific seroreactivity to ∆Np73 isoforms shows higher diagnostic ability in colorectal cancer patients than the canonical p73 protein
Authors: Garranzo-Asensio María , Guzmán-Aránguez Ana , Povés Carmen , Fernández-Aceñero María Jesús , Montero-Calle Ana , Ceron María Ángeles , Fernandez-Diez Servando , Rodríguez Nuria , Gómez de Cedrón Marta , Ramírez de Molina Ana , Domínguez Gemma , Barderas Rodrigo 
Published: September 2019

AbstractThe p53-family is tightly regulated at transcriptional level. Due to alternative splicing, up to 40 different theoretical proteoforms have been described for p73 and at least 20 and 10 for p53 and p63, respectively. However, only the canonical proteins have been evaluated as autoantibody targets in cancer patients for diagnosis. In this study, we have cloned and expressed in vitro the most upregulated proteoforms of p73, ΔNp73α and ΔNp73β, for the analysis of their seroreactivity by a developed luminescence based immunoassay test using 145 individual plasma from colorectal cancer, premalignant individuals and healthy controls. ∆Np73α seroreactivity showed the highest diagnostic ability to discriminate between groups. The combination of ∆Np73α, ∆Np73β and p73 proteoforms seroreactivity were able to improve their individual diagnostic ability. Competitive inhibition experiments further demonstrated the presence of unique specific epitopes in ΔNp73 isoforms not present in p73, with several colorectal patients showing unique and specific seroreactivity to the ΔNp73 proteoforms. Overall, we have increased the complexity of the humoral immune response to the p53-family in cancer patients, showing that the proteoforms derived from the alternative splicing of p73 possess a higher diagnostic ability than the canonical protein, which might be extensive for p53 and p63 proteins.
Interfocal heterogeneity challenges the clinical usefulness of molecular classification of primary prostate cancer
Authors: Carm Kristina Totland , Hoff Andreas M. , Bakken Anne Cathrine , Axcrona Ulrika , Axcrona Karol , Lothe Ragnhild A. , Skotheim Rolf I. , Løvf Marthe 
Published: September 2019

AbstractProstate cancer is a highly heterogeneous disease and typically multiple distinct cancer foci are present at primary diagnosis. Molecular classification of prostate cancer can potentially aid the precision of diagnosis and treatment. A promising genomic classifier was published by The Cancer Genome Atlas (TCGA), successfully classifying 74% of primary prostate cancers into seven groups based on one cancer sample per patient. Here, we explore the clinical usefulness of this classification by testing the classifier’s performance in a multifocal context. We analyzed 106 cancer samples from 85 distinct cancer foci within 39 patients. By somatic mutation data from whole-exome sequencing and targeted qualitative and quantitative gene expression assays, 31% of the patients were uniquely classified into one of the seven TCGA classes. Further, different samples from the same focus had conflicting classification in 12% of the foci. In conclusion, the level of both intra- and interfocal heterogeneity is extensive and must be taken into consideration in the development of clinically useful molecular classification of primary prostate cancer.
The diversity and ecological roles of Penicillium in intertidal zones
Authors: Park Myung Soo , Oh Seung-Yoon , Fong Jonathan J. , Houbraken Jos , Lim Young Woon 
Published: September 2019

AbstractMembers of the genusPenicilliumare commonly isolated from various terrestrial and marine environments, and play an important ecological role as a decomposer. To gain insight into the ecological role ofPenicilliumin intertidal zones, we investigated thePenicilliumdiversity and community structure using a culture-dependent technique and a culture independent metagenomic approach using ITS (ITS-NGS) and partial β-tubulin (BenA-NGS) as targets. The obtained isolates were tested for halotolerance, enzyme activity, and polycyclic aromatic hydrocarbons (PAHs) degradation. A total of 96Penicilliumspecies were identified from the investigated intertidal zones. Although theBenA-NGS method was efficient for detectingPenicillium, some species were only detected using conventional isolation and/or the ITS-NGS method. ThePenicilliumcommunity displayed a significant degree of variation relative to season (summer and winter) and seaside (western and southern coast). ManyPenicilliumspecies isolated in this study exhibited cellulase and protease activity, and/or degradation of PAHs. These findings support the important role ofPenicilliumin the intertidal zone for nutrient recycling and pollutant degradation.
Quantum computational universality of hypergraph states with Pauli-X and Z basis measurements
Authors: Takeuchi Yuki , Morimae Tomoyuki , Hayashi Masahito 
Published: September 2019

AbstractMeasurement-based quantum computing is one of the most promising quantum computing models. Although various universal resource states have been proposed so far, it was open whether only two Pauli bases are enough for both of universal measurement-based quantum computing and its verification. In this paper, we construct a universal hypergraph state that only requires X and Z-basis measurements for universal measurement-based quantum computing. We also show that universal measurement-based quantum computing on our hypergraph state can be verified in polynomial time using only X and Z-basis measurements. Furthermore, in order to demonstrate an advantage of our hypergraph state, we construct a verifiable blind quantum computing protocol that requires only X and Z-basis measurements for the client.
Defining a historic football team: Using Network Science to analyze Guardiola’s F.C. Barcelona
Authors: Buldú J. M. , Busquets J. , Echegoyen I. , Seirul.lo F. 
Published: September 2019

AbstractThe application of Network Science to social systems has introduced new methodologies to analyze classical problems such as the emergence of epidemics, the arousal of cooperation between individuals or the propagation of information along social networks. More recently, the organization of football teams and their performance have been unveiled using metrics coming from Network Science, where a team is considered as a complex network whose nodes (i.e., players) interact with the aim of overcoming the opponent network. Here, we combine the use of different network metrics to extract the particular signature of the F.C. Barcelona coached by Guardiola, which has been considered one of the best teams along football history. We have first compared the network organization of Guardiola’s team with their opponents along one season of the Spanish national league, identifying those metrics with statistically significant differences and relating them with the Guardiola’s game. Next, we have focused on the temporal nature of football passing networks and calculated the evolution of all network properties along a match, instead of considering their average. In this way, we are able to identify those network metrics that enhance the probability of scoring/receiving a goal, showing that not all teams behave in the same way and how the organization Guardiola’s F.C. Barcelona is different from the rest, including its clustering coefficient, shortest-path length, largest eigenvalue of the adjacency matrix, algebraic connectivity and centrality distribution.