bluuebunny/crossref_metadata_2025_split huggingface dataset:
mTORC1 signaling is not essential for the maintenance of muscle mass and function in adult sedentary mice
Authors: Ham Alexander S. , Chojnowska Kathrin , Tintignac Lionel A. , Lin Shuo , Schmidt Alexander , Ham Daniel J. , Sinnreich Michael , Rüegg Markus A. 
Published: August 2019

AbstractBackgroundThe balance between protein synthesis and degradation (proteostasis) is a determining factor for muscle size and function. Signaling via the mammalian target of rapamycin complex 1 (mTORC1) regulates proteostasis in skeletal muscle by affecting protein synthesis and autophagosomal protein degradation. Indeed, genetic inactivation of mTORC1 in developing and growing muscle causes atrophy resulting in a lethal myopathy. However, systemic dampening of mTORC1 signaling by its allosteric inhibitor rapamycin is beneficial at the organismal level and increases lifespan. Whether the beneficial effect of rapamycin comes at the expense of muscle mass and function is yet to be established.MethodsWe conditionally ablated the gene coding for the mTORC1-essential component raptor in muscle fibers of adult mice (iRAmKO). We performed detailed phenotypic and biochemical analyses of iRAmKO mice and compared them with RAmKO mice, which lack raptor in developing muscle fibers. We also used polysome profiling and proteomics to assess protein translation and associated signaling in skeletal muscle of iRAmKO mice.ResultsAnalysis at different time points reveal that, as in RAmKO mice, the proportion of oxidative fibers decreases, but slow-type fibers increase in iRAmKO mice. Nevertheless, no significant decrease in body and muscle mass, or muscle fiber area was detected up to 5 months post-raptor depletion. Similarly, ex vivo muscle force was not significantly reduced in iRAmKO mice. Despite stable muscle size and function, inducible raptor depletion significantly reduced the expression of key components of the translation machinery and overall translation rates.ConclusionsRaptor depletion and hence complete inhibition of mTORC1 signaling in fully-grown muscle leads to metabolic and morphological changes without inducing muscle atrophy even after 5 months. Together, our data indicate that maintenance of muscle size does not require mTORC1 signaling, suggesting that rapamycin treatment is unlikely to negatively affect muscle mass and function.
Theta Phase-Dependent Modulation of Perception by Concurrent tACS and Periodic Visual Stimulation
Authors: Somer Elif , Allen John , Brooks Joseph , Buttrill Vaughan , Javadi Amir-Homayoun 
Published: August 2019

AbstractBackgroundSensory perception can be modulated by the phase of neural oscillations, especially in the theta and alpha ranges. Oscillatory activity in the visual cortex can be entrained by transcranial alternating current stimulation (tACS) as well as periodic visual stimulation (i.e., flicker). Combined tACS and visual flicker stimulation modulates blood-oxygen-level-dependent (BOLD) responses and concurrent 4 Hz auditory click-trains and tACS modulates auditory perception in a phase-dependent way.ObjectiveIn the present study, we investigated if phase synchrony between concurrent tACS and periodic visual stimulation (i.e., flicker) can modulate performance on a visual matching task.MethodsParticipants completed a visual matching task on a flickering visual stimulus while receiving either in-phase (0 degree) or asynchronous (180, 90, or 270 degrees) tACS at alpha or theta frequency. Stimulation was applied over either occipital cortex or dorsolateral prefrontal cortex (DLPFC).ResultsVisual performance was significantly better during theta frequency tACS over the visual cortex when it was in-phase (0 degree) with visual stimulus flicker, compared to anti-phase (180 degree). This effect did not appear with alpha frequency flicker or with DLPFC stimulation. Furthermore, a control sham group showed no effect. There were no significant performance differences amongst the asynchronous (180, 90, and 270 degrees) phase conditions.ConclusionExtending previous studies on visual and auditory perception, our results support a crucial role of oscillatory phase in sensory perception and demonstrate a behaviourally relevant combination of visual flicker and tACS. The spatial and frequency specificity of our results have implications for research on the functional organisation of perception.
Two real use cases of FAIR maturity indicators in the life sciences
Authors: Bonaretti Serena , Willighagen Egon 
Published: August 2019

AbstractData sharing and reuse are crucial to enhance scientific progress and maximize return of investments in science. Although attitudes are increasingly favorable, data reuse remains difficult for lack of infrastructures, standards, and policies. The FAIR (findable, accessible, interoperable, reusable) principles aim to provide recommendations to increase data reuse. Because of the broad interpretation of the FAIR principles, maturity indicators are necessary to determine FAIRness of a dataset. In this work, we propose a reproducible computational workflow to assess data FAIRness in the life sciences. Our implementation follows principles and guidelines recommended by the maturity indicator authoring group and integrates concepts from the literature. In addition, we propose a FAIR balloon plot to summarize and compare dataset FAIRness. We evaluated our method on two real use cases where researchers looked for datasets to answer their scientific questions. We retrieved information from repositories (ArrayExpress and Gene Expression Omnibus), a registry of repositories (re3data.org), and a searchable resource (Google Dataset Search) via application program interface (API) wherever possible. With our analysis, we found that the two datasets met the majority of the criteria defined by the maturity indicators, and we showed areas where improvements can easily be reached. We suggest that use of standard schema for metadata and presence of specific attributes in registries of repositories could increase FAIRness of datasets.
Cortical Overgrowth in a Preclinical Forebrain Organoid Model of CNTNAP2-Associated Autism Spectrum Disorder
Authors: de Jong Job O. , Llapashtica Ceyda , Strauss Kevin , Provenzano Frank , Sun Yan , Cortese Giuseppe P. , Brigatti Karlla W. , Corneo Barbara , Migliori Bianca , Kushner Steven A. , Kellendonk Christoph , Javitch Jonathan A. , Xu Bin , Markx Sander 
Published: August 2019

ABSTRACTAutism spectrum disorder (ASD) represents a major public health burden but translating promising treatment findings from preclinical non-human models of ASD to the clinic has remained challenging. The recent development of forebrain organoids generated from human induced pluripotent stem cells (hiPSCs) derived from subjects with brain disorders is a promising method to study human-specific neurobiology, and may facilitate the development of novel therapeutics.In this study, we utilized forebrain organoids generated from hiPSCs derived from patients from the Old Order Amish community with a rare syndromic form of ASD, carrying a homozygous c.3709DelG mutation in CNTNAP2 and healthy controls to investigate the effects of this mutation on cortical embryonic development.Patients carrying the c.3709DelG mutation in CNTNAP2 present with an increased head circumference and brain MRI reveals an increase in gray matter volume. Patient-derived organoids displayed an increase in total volume that was driven by an increased proliferation in neural progenitor cells, leading to an increase in the generation of cortical neuronal and non-neuronal cell types. The observed phenotypes were rescued after correction of the pathogenic mutation using CRISPR-Cas9. RNA sequencing revealed 339 genes differentially expressed between patient- and control-derived organoids of which a subset are implicated in cell proliferation and neurogenesis. Notably, these differentially expressed genes included previously identified ASD-associated genes and are enriched for genes in ASD-associated weighted gene co-expression networks.This work provides a critical step towards understanding the role of CNTNAP2 in human cortical development and has important mechanistic implications for ASD associated with brain overgrowth. This CNTNAP2 organoid model provides opportunity for further mechanistic inquiry and development of new therapeutic strategies for ASD.
Association of extent of cannabis use and psychotic like intoxication experiences in a multi-national sample of First Episode Psychosis patients and controls
Authors: Sami Musa , Quattrone Diego , Ferraro Laura , Tripoli Giada , Cascia Erika La , Gayer-Anderson Charlotte , Selten Jean-Paul , Arango Celso , Bernardo Miguel , Tarricone Ilaria , Tortelli Andrea , Gatto Giusy , del Peschio Simona , Del-Ben Cristina Marta , Rutten Bart P. , Jones Peter B. , van Os Jim , de Haan Lieuwe , Morgan Craig , Lewis Cathryn , Bhattacharyya Sagnik , Freeman Tom P , Lynskey Michael , Murray Robin M. , Forti Marta Di 
Published: August 2019

AbstractAimsFirst Episode Psychosis (FEP) patients who use cannabis experience more frequent psychotic and euphoric intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in FEP patients and controls and whether this differs between groups.MethodsWe analysed data on lifetime cannabis using patients (n=655) and controls (n=654) across 15 sites from six countries in the EU-GEI study (2010-2015). We used multiple regression to model predictors of cannabis-induced experiences and to determine if there was an interaction between caseness and extent of use.ResultsCaseness, frequency of cannabis use and money spent on cannabis predicted psychotic-like and euphoric experiences, independent of other experiences (p≤0.001). For psychotic-like experiences there was a significant interaction for caseness x frequency of use (p<0.001) and caseness x money spent on cannabis (p=0.001) such that FEP patients had increased experiences at increased levels of use compared to controls. There was no similar significant interaction for euphoric experiences (p>0.5).Conclusions and RelevanceFEP patients are particularly sensitive to increased psychotic-like, but not euphoric experiences, at higher frequency and amount of cannabis use compared to controls. This suggests a specific psychotomimetic response in patients related particularly to heavy cannabis use.
Structure ofS. pombetelomerase protein Pof8 C-terminal domain is an xRRM conserved among LARP7 proteins
Authors: Basu Ritwika , Eichhorn Catherine D. , Cheng Ryan , Feigon Juli 
Published: August 2019

AbstractLa related proteins group 7 (LARP7) are a class of RNA chaperones that bind the 3’ends of RNA and are constitutively associated with their specific target RNAs. In metazoa, Larp7 binds to the long non-coding 7SK RNA as a core component of the 7SK RNP, a major regulator of eukaryotic transcription. In ciliates, a LARP7 protein (p65 inTetrahymena) is a core component of telomerase, an essential ribonucleoprotein complex that maintains the DNA length at eukaryotic chromosome ends. p65 is important for the ordered assembly of telomerase RNA (TER) with telomerase reverse transcriptase (TERT). Although a LARP7 as a telomerase holoenzyme component was initially thought to be specific to ciliate telomerases,Schizosaccharomyces pombePof8 was recently identified as a LARP7 protein and a core component of fission yeast telomerase essential for biogenesis. There is also evidence that human Larp7 associates with telomerase. LARP7 proteins have conserved N-terminal La motif and RRM1 (La module) and C-terminal RRM2 with specific RNA substrate recognition attributed to RRM2, first structurally characterized in p65 as an atypical RRM named xRRM. Here we present the X-ray crystal structure and NMR studies ofS. pombePof8 RRM2. Sequence and structure comparison of Pof8 RRM2 to p65 and hLarp7 xRRMs reveals conserved features for RNA binding with the main variability in the length of the non-canonical helix α3. This study shows that Pof8 has conserved xRRM features, providing insight into TER recognition and the defining characteristics of the xRRM.HighlightsThe structure of theS. pombeLARP7 Pof8 C-terminal domain is an xRRM.Ciliates, human, and fission yeast contain LARP7 proteins with xRRMs involved in telomerase biogenesis.With three examples of xRRM structures, we refine the definition of xRRM.
Supporting evidence for DNA shearing as a mechanism for origin unwinding in eukaryotes
Authors: Langston Lance D. , Georgescu Roxana , O’Donnell Mike E. 
Published: August 2019

ABSTRACTOur earlier study demonstrated that head-to-head CMGs that encircle duplex DNA and track inward at origins, melt double-strand (ds) DNA while encircling the duplex by pulling on opposite strands and shearing DNA apart (Langston and O’Donnell (2019) eLife9, e46515). We show here that increasing the methylphosphonate neutral DNA from 10 nucleotides in the previous report, to 20 nucleotides, reveals that CMG encircling duplex DNA only interacts with the tracking strand compared to the non-tracking strand. This significantly enhances support that CMG tracks on duplex DNA by binding only one strand. Furthermore, EMSA assays using AMPPNP to load CMG onto DNA shows a stoichiometry of only 2 CMGs on an origin mimic DNA, containing a 150 bp duplex with two 3 prime single-strand (ss) tails, one on each end, enabling assay of dsDNA unwinding by a shearing force produced by only two head-to-head CMGs. The use of non-hydrolysable AMPPNP enabled a preincubation for CMG binding the two 3 prime tailed origin mimic DNA, and gave robust unwinding of dsDNA by head-to-head CMG-Mcm10’s. With this precedent, it is possible to envision that the cell may utilize opposing dsDNA motors to unwind DNA for other types of DNA transactions besides origin unwinding.
Operation of photon diagnostic imagers for beam commissioning at the European XFEL
Authors: Koch Andreas , Risch Johannes , Freund Wolfgang , Maltezopoulos Theophilos , Planas Marc , Grünert Jan 
Published: August 2019

X-ray photon beam diagnostic imagers are located at 24 positions in the European XFEL beam transport system to characterize the X-ray beam properties, and to give feedback for tuning and optimization of the electron acceleration and orbit, the undulators, and the X-ray optics. One year of commissioning allowed experience to be gained with these imagers, which will be reported here. The sensitive Spontaneous Radiation imager is useful for various investigations in spontaneous radiation mode: for undulator adjustments and for low-signal imaging applications. The high-resolution Free-Electron Laser imager, 10 µm spatial resolution, is extensively used for the monitoring of beam position, spot size and shape, gain curve measurements, and also for beam-intensity monitoring. The wide field-of-view pop-in monitors (up to 200 mm) are regularly used for alignment and tuning of the various X-ray optical components like mirrors, slits and monochromators, and also for on-line beam control of a stable beam position at the instruments. The Exit Slit imager after the soft X-ray monochromator provides spectral information of the beam together with multi-channel plate based single-pulse gating. For particular use cases, these special features of the imagers are described. Some radiation-induced degradation of scintillators took place in this initial commissioning phase, providing useful information for better understanding of damage thresholds. Visible-light radiation in the beam pipe generated by upstream bending magnets caused spurious reflections in the optical system of some of the imagers which can be suppressed by aluminium-coated scintillating screens.
Galvanic corrosion of electronic material copper coupled silver-coating in electronic systems
Authors: Huang Hualiang , Bu Furong 
Published: August 2019

Purpose
The purpose of this study is to provide a theoretical basis for the study of the galvanic corrosion mechanism of copper coupled silver-coating under a thin electrolyte layer in electronic systems.

Design/methodology/approach
Electrochemical measurements and surface characterizations.

Findings
The results indicate that the potential difference between copper and silver electrodes first quickly increases, and then reaches a relatively stable and large value with the extension of the immersion time. With the significant increase in the cathode/anode area ratio in electronic systems, the area ratio effect obviously accelerates the corrosion of copper due to the remarkable promotion of the cathode process. For a large cathode/anode area ratio, the galvanic current density always maintains a large value and exhibits an increasing trend with the extension of the immersion time, which is attributed that the area ratio effect reduces the protection of corrosion products. For the same area of cathode and anode, the galvanic current density always maintains a small value with the extension of the immersion time due to a low galvanic effect and protective corrosion products.

Practical implications
This work provides some information for the establishment of reliably protective measures for electronic systems in service.

Social implications
This work not only provides some information for the establishment of reliably protective measures for electronic systems in service, but also provides a theoretical basis for the selection of metal materials in microelectronic systems.

Originality/value
This work provides not only a theoretical basis for the study of the galvanic corrosion mechanism of Cu/Ag under a thin electrolyte layer, but also provides some information for the establishment of reliably protective measures for electronic systems in service.
The early development of International New Ventures: a multidimensional exploration
Authors: Kirwan Paul , Ratinho Tiago , van der Sijde Peter , Groen Aard J. 
Published: August 2019

PurposeThe purpose of this paper is to investigate the early development stages of International New Ventures (INVs). Specifically, the authors explore how INVs acquire and leverage four kinds of capital – strategic, managerial, financial and social – to recognise a foreign opportunity, begin the pre-foreign entry activities, and finally start the INV.Design/methodology/approachA stage-based, multidimensional framework was used to investigate how INVs acquire and use the four capitals throughout the internationalisation process. Drawing on four case studies of high-tech INVs, this study tracks their development in three stages: foreign opportunity, pre-foreign operation and post-foreign operation.FindingsResults indicate INVs build advantages and internationalisation activities occur before formal operations begin. INVs deliberately orchestrate certain kinds of capital contingent to the specific internationalisation stage. Further, the authors find that not all types of capital are equally important throughout the internationalisation process: INVs identify foreign opportunities when endowed with managerial and social capital; INVs source a majority of their managerial and financial capitals externally before internationalising; and INVs only contribute all four capitals simultaneously after internationalising.Research limitations/implicationsFindings contribute to knowledge about the development of INVs pre-internationalisation and pre-founding. The study is limited to a comparative sample of INVs, which impacts the generalisability. However, the findings provide a starting point for investigating similar effects using more representative samples.Practical implicationsEntrepreneurs can be proactive in networking activities to allow them greater opportunity to interact with potential resource providers dependent on the stage of internationalisation.Originality/valueThis study contributes to the international entrepreneurship literature with qualitative evidence of the micro-level processes of internationalisation. Very few studies investigate the early, pre-internationalisation and pre-foundation, development stages of INVs.
Changing facets of higher education in management: a students’ perspective
Authors: Rastogi Shailesh , Sharma Arpita , Panse Chetan Padmakar 
Published: August 2019

PurposeThe purpose of this paper is to explore the determinants of effective teaching–learning (ETL) from students’ perspective in B-schools and build a model for the satisfaction of students of B-schools from teaching–learning processes.Design/methodology/approachThe study employs the descriptive research design, and the cross-sectional data are collected through a structured questionnaire. Out of 320, 302 accurately filled questionnaires were used for the empirical analysis. The data are collected from the masters of business management (MBA) students. An exploratory factor analysis is applied to appraise factors appropriate for ETL. A confirmatory factor analysis is used to establish reliability and validity of the identified factors. Structural equation modeling (SEM) is applied to empirically test the proposed model for ETL.FindingsThe major findings of the current study are as follows: this paper identifies extracurricular activities (ECA), conducive environment (CE) and project work and practical exposure (PWPE) as the determinants of ETL in MBA Programs. These determinants have been identified individually; however, collectively authors do not find any other study that discusses them. This paper explores a suitable and apt model of ETL through the identified determinants of ETL (ECA, CE and PWPE). This is also a contribution of the paper, which has not been observed by the authors, in the literature.Research limitations/implicationsThe scope of the research can be enhanced to the all level of management students and colleges of all sorts can be taken.Practical implicationsFindings of this paper are a long-term plan with a futuristic vision. Determinants affecting ETL will help the administrators and faculty members at the MBA programs to realign their focus for the future.Originality/valueThis study determines three determinants (from the students’ points of view) for the effectiveness of the teaching–learning process in the management (MBA) programs. The determinants in this study are ECA, CE and PWPE. SEM is applied to test the model of ETL and to specify these three determinants (constructs). Decision makers for MBA programs can prudently use the model to bring about transformation in teaching–learning processes in business schools.