bluuebunny/crossref_metadata_2025_split huggingface dataset:
The National Health Service (NHS) at 70: Bevan’s double-edged legacy
Authors: Klein Rudolf 
Published: January 2018

AbstractThe paper analyses the achievements and problems stemming from Nye Bevan’s model of a tax funded national health care system, on the assumption that only so could equity be achieved. The evidence shows that indeed the National Health Service (NHS) scores highly on equity, so vindicating Bevan’s vision. The price paid is that fiscal crises are the norm for the NHS, with ever more centralisation, intensive regulation and performance management. Successive reorganisations represent attempts to square the circle – to combine the strengths of Bevan’s model and those of a less hierarchic system – but have so far failed to deliver and can be expected to continue.
A new peculiar species of the genus Helius Lepeletier & Serville, 1828 (Diptera, Limoniidae) from Cretaceous Álava amber (Spain)
Authors: Kania Iwona , Krzemiński Wiesław , Arillo Antonio 
Published: January 2018

ABSTRACTHelius spiralensis sp. nov., is a very peculiar species of the genus Helius (Diptera: Limoniidae), with a characteristic morphology of hypopygium not found in other representatives of this genus. This is the second Helius species described from Early Cretaceous Álava amber (Spain), and one of the oldest representatives of the genus.
The oldest Trichoceridae (Diptera) from the Lower Jurassic of Kyrgyzstan: implications of the biomechanical properties of their wings
Authors: Krzemińska Ewa , Lukashevich Elena 
Published: January 2018

ABSTRACTHere is described the oldest known species of Trichoceridae, from Sogyuty, near lake Issyk-Kul (Kyrgyzstan; Lower Jurassic: Sinemurian). The species is placed in the genus Mailotrichocera Kalugina, 1985in Kalugina & Kovalev (1985), based on isolated wings. The venation of fossil and Recent Trichoceridae is discussed in terms of the biomechanical properties of the wings. The wings of the stem lineage of the family, characterised by a short subcostal vein, also had a larger distal supporting sector than younger lineages, including Recent representatives.
On the systematic position of a highly derived amphiesmenopteran insect from Burmese amber (Insecta, Amphiesmenoptera)
Authors: Mey Wolfram , Wichard Wilfried , Ross Emma , Ross Andrew 
Published: January 2018

ABSTRACTA small fossil insect with scales on the wings and body was identified as a representative of Aphiesmenoptera from Burmese amber. The species is introduced here as Tarachocelis microlepidopterella (†). The insect is described in detail, and photos and line drawings are provided for wing venation, head, mouthparts, scales, legs and abdomen. All characters shared with primitive Lepidoptera and Trichoptera are symplesiomorphies or groundplan traits of Amphiesmenoptera. In addition, the Burmese fossil has a number of remarkable autapomorphies, giving it an appearance that deviates clearly from known families of Lepidoptera and Trichoptera. The species, representing a family of its own, Tarachocelidae, is considered a separate and unique taxon in the stem-group of Amphiesmenoptera and is provisionally placed as Amphiesmenoptera incertae sedis.**NB: See Note Added in Proof (Section 4).
Strengthening IHL protecting persons deprived of their liberty: Main aspects of the consultations and discussions since 2011
Authors: Rodenhäuser Tilman 
Published: January 2018

AbstractOne key area in which international humanitarian law (IHL) needs strengthening is the protection of persons deprived of their liberty in relation to non-international armed conflicts (NIACs). While the Geneva Conventions contain more than 175 rules regulating deprivation of liberty in relation to international armed conflicts in virtually all its aspects, no comparable legal regime applies in NIAC. Since 2011, States and the International Committee of the Red Cross (ICRC) have worked jointly on ways to strengthen IHL protecting persons deprived of their liberty. Between 2011 and 2015, the ICRC facilitated consultations to identify options and recommendations to strengthen detainee protection in times of armed conflict; since 2015, the objective of the process has shifted towards work on one or more concrete and implementable outcomes. The present note recalls the legal need to strengthen detainee protection in times of NIAC and the main steps that have been taken over the past years to strengthen IHL.
Pathway design using de novo steps through uncharted biochemical spaces
Authors: Kumar Akhil , Wang Lin , Ng Chiam Yu , Maranas Costas D. 
Published: January 2018

AbstractExisting retrosynthesis tools generally traverse production routes from a source to a sink metabolite using known enzymes or de novo steps. Generally, important considerations such as blending known transformations with putative steps, complexity of pathway topology, mass conservation, cofactor balance, thermodynamic feasibility, microbial chassis selection, and cost are largely dealt with in a posteriori fashion. The computational procedure we present here designs bioconversion routes while simultaneously considering any combination of the aforementioned design criteria. First, we track and codify as rules all reaction centers using a prime factorization-based encoding technique (rePrime). Reaction rules and known biotransformations are then simultaneously used by the pathway design algorithm (novoStoic) to trace both metabolites and molecular moieties through balanced bio-conversion strategies. We demonstrate the use of novoStoic in bypassing steps in existing pathways through putative transformations, assembling complex pathways blending both known and putative steps toward pharmaceuticals, and postulating ways to biodegrade xenobiotics.
Formation and dynamics of a solar eruptive flux tube
Authors: Inoue Satoshi , Kusano Kanya , Büchner Jörg , Skála Jan 
Published: January 2018

AbstractSolar eruptions are well-known drivers of extreme space weather, which can greatly disturb the Earth’s magnetosphere and ionosphere. The triggering process and initial dynamics of these eruptions are still an area of intense study. Here we perform a magnetohydrodynamic simulation taking into account the observed photospheric magnetic field to reveal the dynamics of a solar eruption in a real magnetic environment. In our simulation, we confirmed that tether-cutting reconnection occurring locally above the polarity inversion line creates a twisted flux tube, which is lifted into a toroidal unstable area where it loses equilibrium, destroying the force-free state, and driving the eruption. Consequently, a more highly twisted flux tube is built up during this initial phase, which can be further accelerated even when it returns to a stable area. We suggest that a nonlinear positive feedback process between the flux tube evolution and reconnection is the key to ensure this extra acceleration.
HLA-B, HLA-C and KIR improve the predictive value of IFNL3 for Hepatitis C spontaneous clearance
Authors: Frias Mario , Rivero-Juárez Antonio , Rodriguez-Cano Diego , Camacho Ángela , López-López Pedro , Risalde María Ángeles , Manzanares-Martín Bárbara , Brieva Teresa , Machuca Isabel , Rivero Antonio 
Published: January 2018

AbstractIFNL3 is the strongest predictor of spontaneous resolution (SR) of hepatitis C virus (HCV), however, consideration of IFNL3 genotype alone is of limited clinical value for the prediction of SR or chronic HCV infection. The objective of this study was to analyze the impact of HLA-B, HLA-C and KIRs on SR, as well as their additive effects on the predictive value of the IFNL3 genotype. We conducted a retrospective study of HIV patients that included both SR and chronic HCV patients. In our study, 61.6% of patients with IFNL3 CC achieved SR, and 81.5% with non-CC genotypes did not achieve SR. HLA-B*44, HLA-C*12, and KIR3DS1 were identified as predictive factors for SR, with percentages of 77.4%, 85.7% and 86.2%, respectively, for patients who did not experience SR. The presence of at least one of these three markers, defined as a genetically unfavorable profile (GUP), combined with the IFNL3 non-CC genotype showed a value of 100% for non-SR. The absence of the three markers, defined as a genetically favorable profile (GFP), in addition to the IFNL3 CC genotype showed a percentage of 74.1% for SR. The combination of these markers in addition to the IFNL3 genotype improves the predictive value of IFNL3 for SR of acute HCV infection in HIV patients, which would be clinically valuable.
High STAP1 expression in DUX4-rearranged cases is not suitable as therapeutic target in pediatric B-cell precursor acute lymphoblastic leukemia
Authors: Steeghs Elisabeth M. P. , Bakker Marjolein , Hoogkamer Alex Q. , Boer Judith M. , Hartman Quirine J. , Stalpers Femke , Escherich Gabriele , de Haas Valerie , de Groot-Kruseman Hester A. , Pieters Rob , den Boer Monique L. 
Published: January 2018

AbstractApproximately 25% of the pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cases are genetically unclassified. More thorough elucidation of the pathobiology of these genetically unclassified (‘B-other’) cases may identify novel treatment options. We analyzed gene expression profiles of 572 pediatric BCP-ALL cases, representing all major ALL subtypes. High expression of STAP1, an adaptor protein downstream of the B-cell receptor (BCR), was identified in BCR-ABL1-like and non-BCR-ABL1-like B-other cases. Limma analysis revealed an association between high expression of STAP1 and BCR signaling genes. However, STAP1 expression and pre-BCR signaling were not causally related: cytoplasmic Igμ levels were not abnormal in cases with high levels of STAP1 and stimulation of pre-BCR signaling did not induce STAP1 expression. To elucidate the role of STAP1 in BCP-ALL survival, expression was silenced in two human BCP-ALL cell lines. Knockdown of STAP1 did not reduce the proliferation rate or viability of these cells, suggesting that STAP1 is not a likely candidate for precision medicines. Moreover, high expression of STAP1 was not predictive for an unfavorable prognosis of BCR-ABL1-like and non-BCR-ABL1-like B-other cases. Remarkably, DUX4-rearrangements and intragenic ERG deletions, were enriched in cases harboring high expression of STAP1.
Neural Correlates of Sexual Orientation in Heterosexual, Bisexual, and Homosexual Women
Authors: Safron Adam , Klimaj Victoria , Sylva David , Rosenthal A. M. , Li Meng , Walter Martin , Bailey J. Michael 
Published: January 2018

AbstractWe used fMRI to investigate neural correlates of responses to erotic pictures and videos in heterosexual (N = 26), bisexual (N = 26), and homosexual (N = 24) women, ages 25–50. We focused on the ventral striatum, an area of the brain associated with desire, extending previous findings from the sexual psychophysiology literature in which homosexual women had greater category specificity (relative to heterosexual and bisexual women) in their responses to male and female erotic stimuli. We found that homosexual women’s subjective and neural responses reflected greater bias towards female stimuli, compared with bisexual and heterosexual women, whose responses did not significantly differ. These patterns were also suggested by whole brain analyses, with homosexual women showing category-specific activations of greater extents in visual and auditory processing areas. Bisexual women tended to show more mixed patterns, with activations more responsive to female stimuli in sensory processing areas, and activations more responsive to male stimuli in areas associated with social cognition.
Beta-catenin cleavage enhances transcriptional activation
Authors: Goretsky Tatiana , Bradford Emily M. , Ye Qing , Lamping Olivia F. , Vanagunas Tomas , Moyer Mary Pat , Keller Patrick C. , Sinh Preetika , Llovet Josep M. , Gao Tianyan , She Qing-Bai , Li Linheng , Barrett Terrence A. 
Published: January 2018

AbstractNuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat552). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat552, increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact. Further experiments showed that TCF4 predominantly binds LMW pβ-Cat552in the nucleus of inflamed and cancerous cells. Nuclear chromatin bound localization of LMW pβ-Cat552was blocked in cells by inhibition of proteasomal chymotrypsin-like activity but not by other protease inhibitors. K48 polyubiquitinated FS and LMW β-catenin were increased by treatment with bortezomib. Overexpressedin vitrodouble truncated β-catenin increased transcriptional activity, cell proliferation and growth of tumor xenografts compared to FS β-catenin. Serine 552-> alanin substitution abrogated K48 polyubiquitination, β-catenin nuclear translocation and tumor xenograft growth. These data suggest that a novel proteasome-dependent posttranslational modification of β-catenin enhances transcriptional activation. Discovery of this pathway may be helpful in the development of diagnostic and therapeutic tools in colitis and cancer.
Evidence of subtle genetic structure in the sympatric species Mullus barbatus and Mullus surmuletus (Linnaeus, 1758) in the Mediterranean Sea
Authors: Matić-Skoko Sanja , Šegvić-Bubić Tanja , Mandić Ivana , Izquierdo-Gomez David , Arneri Enrico , Carbonara Pierluigi , Grati Fabio , Ikica Zdravko , Kolitari Jerina , Milone Nicoletta , Sartor Paolo , Scarcella Giuseppe , Tokaç Adnan , Tzanatos Evangelos 
Published: January 2018

AbstractUsing thirteen microsatellite loci for Mullus barbatus and Mullus surmuletus collected in the Mediterranean Sea, the biogeographic boundaries, genetic distribution among and within basins and the impact of prolonged exploitation in both species were investigated as a basis for understanding their population dynamics and for improving Mullus spp. stock management. Different level of diversity indices among these co-occurring species were obtained, with M. barbatus showing higher allele richness and higher mean observed and expected heterozygosity than M. surmuletus. Reduced contemporary effective population size (Ne) and M-ratio values found in both species likely reflects recent demographic changes, due to a combination of high fishing pressures, habitat fragmentation and naturally occurring fluctuations in population size. Different patterns of genetic connectivity among populations sampled within the Mediterranean were observed for both species. Higher genetic structure was found for M. barbatus as opposed to a more homogenous pattern observed in M. surmuletus samples. Adriatic populations, previously considered panmictic and isolated from other Mediterranean regions, showed geographical partitioning within the basin but also population connectivity with the northern Ionian and Tyrrhenian Seas. Our results highlight the need for temporal sampling in understanding the complex pattern of population connectivity in the Mediterranean, particularly for management purposes.
Differentially expressed microRNAs between cattleyak and yak testis
Authors: Xu Chuanfei , Wu Shixin , Zhao Wangsheng , Mipam TserangDonko , Liu Jingbo , Liu Wenjing , Yi Chuanping , Shah Mujahid ali , Yu Shumin , Cai Xin 
Published: January 2018

AbstractCattleyak are interspecific hybrids between cattle and yak, exhibiting the same prominent adaptability as yak and much higher performances than yak. However, male infertility of cattleyak resulted from spermatogenic arrest has greatly restricted their effective utilization in yak breeding. In past decades, much work has been done to investigate the mechanisms of spermatogenic arrest, but little is known about the differences of the post-transcriptional regulators between cattleyak and yak, which may contribute to the impaired spermatogenesis. MiRNAs, a class of endogenous non-coding small RNA, were revealed to play crucial roles in regulating gene expression at post-transcriptional level. In the present study, we identified 50 differentially expressed (DE) known miRNAs and 11 novel miRNAs by using Illumina HISeq and bioinformatic analysis. A total of 50 putative target sites for the 13 DE known miRNAs and 30 for the 6 DE novel miRNAs were identified, respectively. GO and KEGG analyses were performed to reveal the functions of target genes for DE miRNAs. In addition, RT-qPCR was performed to validate the expression of the DE miRNAs and its targets. The identification of these miRNAs may provide valuable information for a better understanding of spermatogenic arrest in cattleyak.
Developing genome-wide SNPs and constructing an ultrahigh-density linkage map in oil palm
Authors: Bai Bin , Wang Le , Zhang Ying Jun , Lee May , Rahmadsyah Rahmadsyah , Alfiko Yuzer , Ye Bao Qing , Purwantomo Sigit , Suwanto Antonius , Chua Nam-Hai , Yue Gen Hua 
Published: January 2018

AbstractOil palm (Elaeis guineensisJacq.) is the leading oil-producing crops and the most important edible oil resource worldwide. DNA markers and genetic linkage maps are essential resources for marker-assisted selection to accelerate genetic improvement. We conducted RAD-seq on an Illumina NextSeq500 to discover genome-wide SNPs, and used the SNPs to construct a linkage map for an oil palm (Tenera) population derived from a cross between a DeliDuraand an AVROSPisifera. The RAD-seq produced 1,076 million single-end reads across the breeding population containing 155 trees. Mining this dataset detected 510,251 loci. After filtering out loci with low accuracy and more than 20% missing data, 11,394 SNPs were retained. Using these SNPs, in combination with 188 anchor SNPs and 123 microsatellites, we constructed a linkage map containing 10,023 markers covering 16 chromosomes. The map length is 2,938.2 cM with an average marker space of 0.29 cM. The large number of SNPs will supply ample choices of DNA markers in analysing the genetic diversity, population structure and evolution of oil palm. This high-density linkage map will contribute to mapping quantitative trait loci (QTL) for important traits, thus accelerating oil palm genetic improvement.
Regulation of metabolism in Escherichia coli during growth on mixtures of the non-glucose sugars: arabinose, lactose, and xylose
Authors: Ammar Ehab M. , Wang Xiaoyi , Rao Christopher V. 
Published: January 2018

AbstractCatabolite repression refers to the process where the metabolism of one sugar represses the genes involved in metabolizing another sugar. While glucose provides the canonical example, many other sugars are also known to induce catabolite repression. However, less is known about the mechanism for catabolite repression by these non-glucose sugars. In this work, we investigated the mechanism of catabolite repression in the bacteriumEscherichia coliduring growth on lactose, L-arabinose, and D-xylose. The metabolism of these sugars is regulated in a hierarchical manner, where lactose is the preferred sugar, followed by L-arabinose, and then D-xylose. Previously, the preferential utilization of L-arabinose over D-xylose was found to result from transcriptional crosstalk. However, others have proposed that cAMP governs the hierarchical regulation of many non-glucose sugars. We investigated whether lactose-induced repression of L-arabinose and D-xylose gene expression is due to transcriptional crosstalk or cAMP. Our results demonstrate that it is due to cAMP and not transcriptional crosstalk. In addition, we found that repression is reciprocal, where both L-arabinose and D-xylose also repress the lactose gene expression, albeit to a lesser extent and also through a mechanism involving cAMP. Collectively, the results further our understanding of metabolism during growth on multiple sugars.
Evidence for sparse synergies in grasping actions
Authors: Prevete Roberto , Donnarumma Francesco , d’Avella Andrea , Pezzulo Giovanni 
Published: January 2018

AbstractConverging evidence shows that hand-actions are controlled at the level of synergies and not single muscles. One intriguing aspect of synergy-based action-representation is that it may be intrinsically sparse and the same synergies can be shared across several distinct types of hand-actions. Here, adopting a normative angle, we consider three hypotheses for hand-action optimal-control:sparse-combination hypothesis (SC)– sparsity in the mapping between synergies and actions - i.e., actions implemented using a sparse combination of synergies;sparse-elements hypothesis (SE)– sparsity in synergy representation – i.e., the mapping between degrees-of-freedom (DoF) and synergies is sparse;double-sparsity hypothesis (DS)– a novel view combining both SC and SE – i.e., both the mapping between DoF and synergies and between synergies and actions are sparse, each action implementing a sparse combination of synergies (as in SC), each using a limited set of DoFs (as in SE). We evaluate these hypotheses using hand kinematic data from six human subjects performing nine different types of reach-to-grasp actions. Our results support DS, suggesting that the best action representation is based on a relatively large set of synergies, each involving a reduced number of degrees-of-freedom, and that distinct sets of synergies may be involved in distinct tasks.
T cell immunity to Zika virus targets immunodominant epitopes that show cross-reactivity with other Flaviviruses
Authors: Reynolds C. J. , Suleyman O. M. , Ortega-Prieto A. M. , Skelton J. K. , Bonnesoeur P. , Blohm A. , Carregaro V. , Silva J. S. , James E. A. , Maillère B. , Dorner M. , Boyton R. J. , Altmann D. M. 
Published: January 2018

AbstractZika virus (ZIKV) Infection has several outcomes from asymptomatic exposure to rash, conjunctivitis, Guillain-Barré syndrome or congenital Zika syndrome. Analysis of ZIKV immunity is confounded by the fact that several related Flaviviruses infect humans, including Dengue virus 1–4, West Nile virus and Yellow Fever virus. HLA class II restricted T cell cross-reactivity between ZIKV and other Flaviviruses infection(s) or vaccination may contribute to protection or to enhanced immunopathology. We mapped immunodominant, HLA class II restricted, CD4 epitopes from ZIKV Envelope (Env), and Non-structural (NS) NS1, NS3 and NS5 antigens in HLA class II transgenic mice. In several cases, ZIKV primed CD4 cells responded to homologous sequences from other viruses, including DENV1–4, WNV or YFV. However, cross-reactive responses could confer immune deviation - the response to the Env DENV4 p1 epitope in HLA-DR1 resulted in IL-17A immunity, often associated with exacerbated immunopathogenesis. This conservation of recognition across Flaviviruses, may encompass protective and/or pathogenic components and poses challenges to characterization of ZIKV protective immunity.