bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver Preservation by Aortic Perfusion Alone Compared With Preservation by Aortic Perfusion and Additional Arterial Ex Situ Back-Table Perfusion With Histidine-Tryptophan-Ketoglutarate Solution: A Prospective, Randomized, Controlled, Multicenter Study
Authors: Otto Gerd , Heise Michael , Thies Jochen , Pitton Michael , Schneider Jens , Kaiser Gernot , Neuhaus Peter , Kollmar Otto , Barthels Michael , Geks Josef , Bechstein Wolf Otto , Hellinger Achim , Klempnauer Jürgen , Padberg Winfried , Frühauf Nils , Ebbing Andre , Mauer Dietmar , Schneider Astrid , Kwiecien Robert , Kronfeld Kai 
Published: June 2017

Background
Arterial ex situ back-table perfusion (BP) reportedly reduces ischemic-type biliary lesion after liver transplantation. We aimed to verify these findings in a prospective investigation.

Methods
Our prospective, randomized, controlled, multicenter study involved livers retrieved from patients in 2 German regions, and compared the outcomes of standard aortic perfusion to those of aortic perfusion combined with arterial ex situ BP. The primary endpoint was the incidence of ischemic-type biliary lesions over a follow-up of 2 years after liver transplantation, whereas secondary endpoints included 2-year graft survival, initial graft damage as reflected by transaminase levels, and functional biliary parameters at 6 months after transplantation.

Results
A total of 75 livers preserved via standard aortic perfusion and 75 preserved via standard aortic perfusion plus arterial BP were treated using a standardized protocol. The incidence of clinically apparent biliary lesions after liver transplantation (n = 9 for both groups; P = 0.947), the 2-year graft survival rate (standard aortic perfusion, 74%; standard aortic perfusion plus arterial BP, 68%; P = 0.34), and incidence of initial graft injury did not differ between the 2 perfusion modes. Although 33 of the 77 patients with cholangiography workups exhibited injured bile ducts, only 10 had clinical symptoms.

Conclusions
Contrary to previous findings, the present study indicated that additional ex situ BP did not prevent ischemic-type biliary lesions or ischemia-reperfusion injury after liver transplantation. Moreover, there was considerable discrepancy between cholangiography findings regarding bile duct changes and clinically apparent cholangiopathy after transplantation, which should be considered when assessing ischemic-type biliary lesions.
Optical atomic phase reference and timing
Authors: Hollberg L. , Cornell E. H. , Abdelrahmann A. 
Published: June 2017

Atomic clocks based on laser-cooled atoms have made tremendous advances in both accuracy and stability. However, advanced clocks have not found their way into widespread use because there has been little need for such high performance in real-world/commercial applications. The drive in the commercial world favours smaller, lower-power, more robust compact atomic clocks that function well in real-world non-laboratory environments. Although the high-performance atomic frequency references are useful to test Einstein's special relativity more precisely, there are not compelling scientific arguments to expect a breakdown in special relativity. On the other hand, the dynamics of gravity, evidenced by the recent spectacular results in experimental detection of gravity waves by the LIGO Scientific Collaboration, shows dramatically that there is new physics to be seen and understood in space–time science. Those systems require strain measurements at less than or equal to 10
−20
. As we discuss here, cold atom optical frequency references are still many orders of magnitude away from the frequency stability that should be achievable with narrow-linewidth quantum transitions and large numbers of very cold atoms, and they may be able to achieve levels of phase stability, Δ
Φ
/
Φ
total
≤ 10
−20
, that could make an important impact in gravity wave science.

This article is part of the themed issue ‘Quantum technology for the 21st century’.
Sparse Bursts Optimize Information Transmission in a Multiplexed Neural Code
Authors: Naud Richard , Sprekeler Henning 
Published: July 2017

AbstractMany cortical neurons combine the information ascending and descending the cortical hierarchy. In the classical view, this information is combined nonlinearly to give rise to a single firing rate output, which collapses all input streams into one. We propose that neurons can simultaneously represent multiple input streams by using a novel code that distinguishes single spikes and bursts at the level of a neural ensemble. Using computational simulations constrained by experimental data, we show that cortical neurons are well suited to generate such multiplexing. Interestingly, this neural code maximizes information for short and sparse bursts, a regime consistent with in vivo recordings. It also suggests specific connectivity patterns that allows to demultiplex this information. These connectivity patterns can be used by the nervous system to maintain optimal multiplexing. Contrary to firing rate coding, our findings indicate that a single neural ensemble can communicate multiple independent signals to different targets.
Combining Ensemble Learning Techniques and G-Computation to Investigate Chemical Mixtures in Environmental Epidemiology Studies
Authors: Oulhote Youssef , Bind Marie-Abele , Coull Brent , Patel Chirag J , Grandjean Philippe 
Published: July 2017

ABSTRACTBackgroundAlthough biomonitoring studies demonstrate that the general population experiences exposure to multiple chemicals, most environmental epidemiology studies consider each chemical separately when assessing adverse effects of environmental exposures. Hence, the critical need for novel approaches to handle multiple correlated exposures.MethodsWe propose a novel approach using the G-formula, a maximum likelihood-based substitution estimator, combined with an ensemble learning technique (i.e. SuperLearner) to infer causal effect estimates for a multi-pollutant mixture. We simulated four continuous outcomes from real data on 5 correlated exposures under four exposure-response relationships with increasing complexity and 500 replications. The first simulated exposure-response was generated as a linear function depending on two exposures; the second was based on a univariate nonlinear exposure-response relationship; the third was generated as a linear exposure-response relationship depending on two exposures and their interaction; the fourth simulation was based on a non-linear exposure-response relationship with an effect modification by sex and a linear relationship with a second exposure. We assessed the method based on its predictive performance (Minimum Square error [MSE]), its ability to detect the true predictors and interactions (i.e. false discovery proportion, sensitivity), and its bias. We compared the method with generalized linear and additive models, elastic net, random forests, and Extreme gradient boosting. Finally, we reconstructed the exposure-response relationships and developed a toolbox for interactions visualization using individual conditional expectations.ResultsThe proposed method yielded the best average MSE across all the scenarios, and was therefore able to adapt to the true underlying structure of the data. The method succeeded to detect the true predictors and interactions, and was less biased in all the scenarios. Finally, we could correctly reconstruct the exposure-response relationships in all the simulations.ConclusionsThis is the first approach combining ensemble learning techniques and causal inference to unravel the effects of chemical mixtures and their interactions in epidemiological studies. Additional developments including high dimensional exposure data, and testing for detection of low to moderate associations will be carried out in future developments.
LINE-1 and the cell cycle: protein localization and functional dynamics
Authors: Mita Paolo , Wudzinska Aleksandra , Sun Xiaoji , Andrade Joshua , Nayak Shruti , Kahler David J. , Badri Sana , LaCava John , Ueberheide Beatrix , Yun Chi Y. , Fenyo David , Boeke Jef D. 
Published: July 2017

AbstractLINE-1/L1 retrotransposon sequences comprise 17% of the human genome. Among the many classes of mobile genetic elements, L1 is the only autonomous retrotransposon that still drives human genomic plasticity today. Through its co-evolution with the human genome, L1 has intertwined itself with host cell biology to aid its proliferation. However, a clear understanding of L1’s lifecycle and the processes involved in restricting its insertion and its intragenomic spreading remains elusive. Here we identify modes of L1 proteins’ entrance into the nucleus, a necessary step for L1 proliferation. Using functional, biochemical, and imaging approaches, we also show a clear cell cycle bias for L1 retrotransposition that peaks during the S phase. Our observations provide a basis for novel interpretations about the nature of nuclear and cytoplasmic L1 ribonucleoproteins (RNPs) and the potential role of DNA replication in L1 retrotransposition.
Multi-BRCT domain protein Brc1 links Rhp18/Rad18 and γH2A to maintain genome stability during S-phase
Authors: Reubens Michael C. , Rozenzhak Sophie , Russell Paul 
Published: June 2017

ABSTRACTDNA replication involves the inherent risk of genome instability, as replisomes invariably encounter DNA lesions or other structures that stall or collapse replication forks during S-phase. In the fission yeastSchizosaccharomyces pombe, the multi-BRCT domain protein Brc1, which is related to budding yeast Rtt107 and mammalian PTIP, plays an important role in maintaining genome integrity and cell viability when cells experience replication stress. The C-terminal pair of BRCT domains in Brc1 were previously shown to bind phospho-histone H2A (γH2A) formed by Rad3/ATR checkpoint kinase at DNA lesions; however, the putative scaffold interactions involving the N-terminal BRCT domains 1-4 of Brc1 have remained obscure. Here we show that these domains bind Rhp18/Rad18, which is an E3 ubiquitin protein ligase that has crucial functions in postreplication repair. A missense allele in BRCT domain 4 of Brc1 disrupts binding to Rhp18 and causes sensitivity to replication stress. Brc1 binding to Rhp18 and γH2A are required for the Brc1-overexpression suppression ofsmc6-74,which impairs the Smc5/6 structural maintenance of chromosomes complex required for chromosome integrity and repair of collapsed replication forks. From these findings we propose that Brc1 provides scaffolding functions linking γH2A, Rhp18, and Smc5/6 complex at damaged replication forks.
CLAPO syndrome: Identification of somatic activatingPIK3CAmutations and delineation of the natural history and phenotype
Authors: Rodriguez-Laguna Lara , Ibañez Kristina , Gordo Gema , Garcia-Minaur Sixto , Santos-Simarro Fernando , Agra Noelia , Vallespín Elena , Fernández-Montaño Victoria E , Martín-Arenas Rubén , del Pozo Ángela , Gonzalez-Pecellín Héctor , Mena Rocío , Rueda-Arenas Inmaculada , Gomez María V. , Villaverde Cristina , Bustamante Ana , Ayuso Carmen , Ruiz-Perez Víctor L. , Nevado Julián , Lapunzina Pablo , Lopez-Gutierrez Juan C. , Martinez-Glez Victor 
Published: June 2017

AbstractBackgroundCLAPO syndrome is a rare vascular disorder characterized by Capillary malformation of the lower lip, Lymphatic malformation predominant on the face and neck, Asymmetry, and Partial/generalized Overgrowth. Although the genetic cause is not known, the tissue distribution of the clinical manifestations in CLAPO seems to follow a pattern of somatic mosaicism.Subjects and methodsWe clinically evaluated a cohort of 13 patients with CLAPO and screened 20 DNA blood/tissue samples from nine patients using high-throughput, deep sequencing.ResultsWe identified five activating mutations in thePIK3CAgene in affected tissues from six of the nine patients studied; one of the variants (NM_006218.2:c.248T>C; p.Phe83Ser) has not been previously described in developmental disorders.ConclusionsWe describe for the first time the presence of somatic activatingPIK3CAmutations in patients with CLAPO. We also report an update of the phenotype and natural history of the syndrome.
A compendium of co-regulated protein complexes in breast cancer reveals collateral loss events
Authors: Ryan Colm J. , Kennedy Susan , Bajrami Ilirjana , Matallanas David , Lord Christopher J. 
Published: June 2017

SummaryProtein complexes are responsible for the bulk of activities within the cell, but how their behavior and composition varies across tumors remains poorly understood. By combining proteomic profiles of breast tumors with a large-scale protein-protein interaction network, we have identified a set of 258 high-confidence protein complexes whose subunits have highly correlated protein abundance across tumor samples. We used this set to identify complexes that are reproducibly under- or over-expressed in specific breast cancer subtypes. We found that mutation or deletion of one subunit of a complex was often associated with a collateral reduction in protein expression of additional complex members. This collateral loss phenomenon was evident from proteomic, but not transcriptomic, profiles suggesting post-transcriptional control. Mutation of the tumor suppressor E-cadherin (CDH1)was associated with a collateral loss of members of the adherens junction complex, an effect we validated using an engineered model of E-cadherin loss.
Activation of somatostatin interneurons by nicotinic modulator Lypd6 enhances plasticity and functional recovery in the adult mouse visual cortex
Authors: Sadahiro Masato , Demars Michael P. , Burman Poromendro , Yevoo Priscilla , Zimmer Andreas , Morishita Hirofumi 
Published: June 2017

AbstractThe limitation of plasticity in the adult brain impedes functional recovery later in life from brain injury or disease. This pressing clinical issue may be resolved by enhancing plasticity in the adult brain. One strategy for triggering robust plasticity in adulthood is to reproduce one of the hallmark physiological events of experience-dependent plasticity observed during the juvenile critical period – rapidly reduce the activity of parvalbumin (PV)-expressing interneurons and disinhibit local excitatory neurons. This may be achieved through enhancement of local inhibitory inputs, particularly those of somatostatin (SST)-expressing interneurons. However, to date the means for manipulating SST interneurons for enhancing cortical plasticity in the adult brain are not known. We show that SST interneuron-selective overexpression of Lypd6, an endogenous nicotinic signaling modulator, enhances ocular dominance plasticity in the adult primary visual cortex (V1). Lypd6 overexpression mediates a rapid experience-dependent increase in the visually evoked activity of SST interneurons as well as a simultaneous reduction in PV interneuron activity and disinhibition of excitatory neurons. Recapitulating this transient activation of SST interneurons using chemogenetics similarly enhanced V1 plasticity. Notably, we show that SST-selective Lypd6 overexpression restores visual acuity in amblyopic mice that underwent early long-term monocular deprivation. Our data in both male and female mice reveal selective modulation of SST interneurons and a putative downstream circuit mechanism as an effective method for enhancing experience-dependent cortical plasticity as well as functional recovery in adulthood.Significance StatementThe decline of cortical plasticity after closure of juvenile critical period consolidates neural circuits and behavior, but this limits functional recovery from brain diseases and dysfunctions in later life. Here we show that activation of cortical SST interneurons by Lypd6, an endogenous modulator of nicotinic acetylcholine receptors (nAChRs), enhances experience-dependent plasticity and recovery from amblyopia in adulthood. This manipulation triggers rapid reduction of PV interneuron activity and disinhibition of excitatory neurons, which are known hallmarks of cortical plasticity during juvenile critical periods. Our study demonstrates modulation of SST interneurons by Lypd6 to achieve robust levels of cortical plasticity in the adult brain and may provide promising targets for restoring brain function in the event of brain trauma or disease.
A Bayesian Framework for Multiple Trait Colocalization from Summary Association Statistics
Authors: Giambartolomei Claudia , Zhenli Liu Jimmy , Zhang Wen , Hauberg Mads , Shi Huwenbo , Boocock James , Pickrell Joe , Jaffe Andrew E. ,   the CommonMind Consortium, Pasaniuc Bogdan , Roussos Panos 
Published: June 2017

AbstractMotivationMost genetic variants implicated in complex diseases by genome-wide association studies (GWAS) are non-coding, making it challenging to understand the causative genes involved in disease. Integrating external information such as quantitative trait locus (QTL) mapping of molecular traits (e.g., expression, methylation) is a powerful approach to identify the subset of GWAS signals explained by regulatory effects. In particular, expression QTLs (eQTLs) help pinpoint the responsible gene among the GWAS regions that harbor many genes, while methylation QTLs (mQTLs) help identify the epigenetic mechanisms that impact gene expression which in turn affect disease risk. In this work we proposemultiple-trait-coloc(moloc), a Bayesian statistical framework that integrates GWAS summary data with multiple molecular QTL data to identify regulatory effects at GWAS risk loci.ResultsWe appliedmolocto schizophrenia (SCZ) and eQTL/mQTL data derived from human brain tissue and identified 52 candidate genes that influence SCZ through methylation. Our method can be applied to any GWAS and relevant functional data to help prioritize disease associated genes.Availabilitymolocis available for download as an R package (https://github.com/clagiamba/moloc). We also developed a web site to visualize the biological findings (icahn.mssm.edu/moloc). The browser allows searches by gene, methylation probe, and scenario of interest.Contactclaudia.giambartolomei@gmail.comSupplementary informationSupplementary data are available atBioinformaticsonline.
Novel ‘housekeeping’ genes and an unusually heterogeneous distribution of transporter expression profiles in human tissues and cell lines, assessed using the Gini coefficient
Authors: O’Hagan Steve , Muelas Marina Wright , Day Philip J. , Lundberg Emma , Kell Douglas B. 
Published: June 2017

AbstractWe analyse two comprehensive transcriptome datasets from human tissues and human-derived cell lines in terms of the expression profiles of the SLC and ABC families of membrane transporters. The Gini index (coefficient) characterises inequalities of distributions, and is used in a novel way to describe the distribution of the expression of each transporter among the different tissues and cell lines. In many cases, transporters exhibit extremely high Gini coefficients, even when their supposed substrates might be expected to be available to all tissues, indicating a much higher degree of specialisation than is usually assumed. This is consistent with divergent evolution from a more restricted set of ancestors. Similar trends hold true for the expression profiles of transporters in different cell lines, suggesting that cell lines exhibit largely similar transport behaviour to that of tissues. By contrast, the Gini coefficients for ABC transporters tend to be larger in cell lines than in tissues, implying that some kind of a selection process has taken place. In particular, with some exceptions such as olfactory receptors and genes involved in keratin production, transporter genes are significantly more heterogeneously expressed than are most non-transporter genes. The Gini index also allows us to determine those transcripts with the most stable expression; these often differ significantly from the ‘housekeeping’ genes commonly used for normalisation in transcriptomics and qPCR studies. The lowest four in tissues are FAM32A, ABCB7, MRPL21 and PCBP1, while the lowest three in cell lines are SF3B2, NXF1 and RBM45. PCBP1 is both reasonably highly expressed and has a low Gini coefficient in both tissues and cell lines, and is an excellent novel housekeeping gene. Overall, our analyses provide novel opportunities for the normalisation of genome-wide expression profiling data.
Alertness fluctuations during task performance modulate cortical evoked responses to transcranial magnetic stimulation
Authors: Noreika Valdas , Kamke Marc R. , Canales-Johnson Andrés , Chennu Srivas , Bekinschtein Tristan A. , Mattingley Jason B. 
Published: June 2017

ABSTRACTTranscranial magnetic stimulation (TMS) has been widely used in human cognitive neuroscience to examine the causal role of distinct cortical areas in perceptual, cognitive and motor functions. However, it is widely acknowledged that the effects of focal cortical stimulation on behaviour can vary substantially between participants and even from trial to trial within individuals. Here we asked whether spontaneous fluctuations in alertness can account for the variability in behavioural and neurophysiological responses to TMS. We combined single-pulse TMS with neural recording via electroencephalography (EEG) to quantify changes in motor and cortical reactivity with fluctuating levels of alertness defined objectively on the basis of ongoing brain activity. We observed rapid, non-linear changes in TMS-evoked neural responses – specifically, motor evoked potentials and TMS-evoked cortical potentials – as EEG activity indicated decreasing levels of alertness, even while participants remained awake and responsive in the behavioural task.IMPACT STATEMENTA substantial proportion of inter-trial variability in neurophysiological responses to TMS is due to spontaneous fluctuations in alertness, which should be controlled for during experimental and clinical applications of TMS.
Regulation of somatosensory mechanotransduction by Annexin A6
Authors: Raouf Ramin , Lolignier Stéphane , Sexton Jane E. , Millet Queensta , Santana-Varela Sonia , Biller Anna , Fuller Alice M. , Pereira Vanessa , Choudhary Jyoti , Collins Mark , Moss Stephen E. , Tordo Julie , Linden Michael , Wood John N 
Published: June 2017

AbstractSensory neuron mechanically-activated slowly adapting currents have been linked to noxious mechanosensation. We identified a Conotoxin, Noxious Mechanosensation Blocker -1, that blocks such currents selectively and inhibits mechanical pain Using an active biotinylated form of the toxin we identified 67 binding proteins in sensory neurons and sensory neuron-derived cell lines using mass spectrometry. Annexin A6 was the most frequently identified binding protein. Annexin A6 knockout mice showed an enhanced sensitivity to mechanical stimuli. An increase in rapidly adapting currents was observed in sensory neurons alongside a decrease in slowly adapting currents. Conversely, overexpression of Annexin A6 in sensory neurons inhibited rapidly adapting currents and augmented slowly adapting currents. Furthermore, co-expression of Annexin A6 with Piezo2 led to an inhibition of Piezo-mediated rapidly adapting currents. AAV-mediated overexpression of Annexin A6 in sensory neurons attenuated mechanical pain in a mouse model of osteoarthritis. These data demonstrate a modulatory role for Annexin A6 in somatosensory mechanotransduction.