bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atg8a interacts with transcription factor Sequoia to control the expression of autophagy genes in Drosophila
Authors: Jacomin Anne-Claire , Petridi Stavroula , DiMonaco Marisa , Jain Ashish , Bhujabal Zambarlal , Mulakkal Nitha , Palara Anthimi , Powell Emma L. , Chung Bonita , Zampronio Cleidiane G. , Jones Alexandra , Cameron Alexander , Johansen Terje , Nezis Ioannis P. 
Published: April 2019

SUMMARYAutophagy is a fundamental, evolutionarily conserved, process in which cytoplasmic material is degraded through the lysosomal pathway [1–7]. One of the most important and well-studied autophagy-related proteins is LC3 [Microtubule-associated protein 1 light chain 3, (called Atg8 in yeast and Drosophila)], which participates in autophagosome formation and autophagy cargo selection in the cytoplasm, and is one of the most widely utilized markers of autophagy [8, 9]. Despite growing evidence that LC3 is enriched in the nucleus, little is known about the mechanisms involved in targeting LC3 to the nucleus and the nuclear components it interacts with [10–13]. Here we show that Drosophila Atg8a protein, homologous to mammalian LC3 and yeast Atg8, interacts with the transcription factor Sequoia in a LIR-motif dependent manner. We show that Sequoia depletion induces autophagy in nutrient rich conditions through enhanced expression of autophagy genes. We also show that Atg8a interacts with YL-1, a component of a nuclear acetyltransferase complex, and is acetylated at position K46. Additionally, we show that Atg8a interacts with the deacetylase Sir2, which deacetylates Atg8a during starvation in order to activate autophagy. Our results suggest a mechanism of regulation of expression of autophagy genes by Atg8a, which is linked to its acetylation status and its interaction with Sequoia, YL-1 and Sir2.
A mobile ELF4 delivers circadian temperature information from shoots to roots
Authors: Chen Wei Wei , Takahashi Nozomu , Hirata Yoshito , Nusinow Dmitri A. , Kay Steve A. , Mas Paloma 
Published: April 2019

AbstractThe circadian clock is synchronized by environmental cues, mostly by light and temperature. Elucidating how the plant circadian clock responds to temperature oscillations is crucial to understand plant responsiveness to the environment. Here we found a prevalent temperature-dependent function of the Arabidopsis clock component ELF4 (EARLY FLOWERING 4) in the root clock. Micrografting assays and mathematical analyses show that ELF4 moves from shoots to regulate rhythms in roots. ELF4 movement does not convey photoperiodic information but trafficking is essential to control the period of the root clock in a temperature-dependent manner. At low temperatures, ELF4 mobility is favored and results in a slow-paced root clock while high temperatures decrease movement, leading to a fast clock. Hence, the mobile ELF4 delivers temperature information and establishes a shoot-to-root dialogue that sets the pace of the clock in roots.
Deep learning for cancer type classification
Authors: Zeng Zexian , Mao Chengsheng , Vo Andy , Nugent Janna Ore , Khan Seema A , Clare Susan E , Luo Yuan 
Published: April 2019

ABSTRACTGenetic information is becoming more readily available and is increasingly being used to predict patient cancer types as well as their subtypes. Most classification methods thus far utilize somatic mutations as independent features for classification and are limited by study power. To address these limitations, we propose DeepCues, a deep learning model that utilizes convolutional neural networks to derive features from DNA sequencing data for disease classification and relevant gene discovery. Using whole-exome sequencing, germline variants and somatic mutations, including insertions and deletions, are interactively amalgamated as features. In this study, we applied DeepCues to a dataset from TCGA to classify seven different types of major cancers and obtained an overall accuracy of 77.6%. We compared DeepCues to conventional methods and demonstrated a significant overall improvement (p=8.8E-25). Using DeepCues, we found that the top 20 genes associated with breast cancer have a 40% overlap with the top 20 breast cancer genes in the COSMIC database. These data support DeepCues as a novel method to improve the representational resolution of both germline variants and somatic mutations interactively and their power in predicting cancer types, as well the genes involved in each cancer.
High specificity of widely used phospho-tau antibodies validated using a quantitative whole-cell based assay
Authors: Li Dan , Cho Yong Ku 
Published: April 2019

AbstractAntibodies raised against defined phosphorylation sites of the microtubule-associated protein tau are widely used in scientific research and being applied in clinical assays. However, recent studies have revealed an alarming degree of non-specific binding found in these antibodies. In order to quantify and compare the specificity phospho-tau antibodies and other post-translational modification site-specific antibodies in general, a measure of specificity is urgently needed. Here we report a robust flow cytometry assay using human embryonic kidney (HEK) cells that enables the determination of a specificity parameter termed Φ, which measures the fraction of non-specific signal in antibody binding. We validate our assay using anti-tau antibodies with known specificity profiles, and apply it to measure the specificity of 7 widely used phospho-tau antibodies (AT270, AT8, AT100, AT180, PHF-6, TG-3, and PHF-1) among others. We successfully determined the Φ values for all antibodies except AT100, which did not show detectable binding in our assay. Our results show that antibodies AT8, AT180, PHF-6, TG-3, and PHF-1 have Φ values near 1, which indicates no detectable non-specific binding. AT270 showed Φ value around 0.8, meaning that approximately 20% of the binding signal originates from non-specific binding. Further analyses using immunocytochemistry and western blotting confirmed the presence of non-specific binding of AT270 to non-tau proteins found in HEK cells and the mouse hippocampus. We anticipate that the quantitative approach and parameter introduced here will be widely adopted as a standard for reporting the specificity for phospho-tau antibodies, and potentially for post-translational modification targeting antibodies in general.
A Bigenic mouse model of FSGS reveals perturbed pathways in podocytes, mesangial cells and endothelial cells
Authors: Potter Andrew S. , Drake Keri , Brunskill Eric W. , Potter S. Steven 
Published: April 2019

AbstractFocal segmental glomerulosclerosis is a major cause of end stage renal disease. Many patients prove unresponsive to available therapies. An improved understanding of the molecular basis of the disease process could provide insights leading to novel therapeutic approaches. In this study we carried out an RNA-seq analysis of the altered gene expression patterns of podocytes, mesangial cells and glomerular endothelial cells of the bigenicCd2ap+/-,Fyn-/- mutant mouse model of FSGS. In the podocytes we observed upregulation of many genes related to the Tgfβ family/pathway, includingGdnf, Tgfβ1, Tgfβ2, Snai2, Vegfb, Bmp4, andTnc. The mutant podocytes also showed upregulation ofActa2, a marker of smooth muscle and associated with myofibroblasts, which are implicated in driving fibrosis. GO analysis of the podocyte upregulated genes identified elevated protein kinase activity, increased expression of growth factors, and negative regulation of cell adhesion, perhaps related to the observed podocyte loss. Both podocytes and mesangial cells showed strong upregulation of aldehyde dehydrogenase genes involved in the synthesis of retinoic acid. Similarly, theCd2ap+/-,Fyn-/- mesangial cells, as well as podocytes in other genetic models, and the glomeruli of human FSGS patients, all show upregulation of the serine protease Prss23, with the common thread suggesting important functionality. Another gene with strong upregulation in theCd2ap+/-,Fyn-/- mutant mesangial cells as well as multiple other mutant mouse models of FSGS was thrombospondin, which activates the secreted inactive form of Tgfβ. TheCd2ap+/-,Fyn-/- mutant endothelial cells showed elevated expression of genes involved in cell proliferation, angioblast migration, angiogenesis, and neovasculature, all consistent with the formation of new blood vessels in the diseased glomerulus. The resulting global definition of the perturbed molecular pathways in the three major cell types of the mutant glomerulus provide deeper understanding of the molecular pathogenic pathways.
The use of strategy tools and frameworks by SMEs in the strategy formation process
Authors: Bellamy Lawrence Charles , Amoo Nii , Mervyn Kieran , Hiddlestone-Mumford Jacqueline 
Published: April 2019

PurposeThe purpose of this study is to examine the use of tools and techniques of strategy and strategic analysis within small- and medium-sized enterprises (SMEs) as a part of the strategy formation process.Design/methodology/approachThis study uses a qualitative, multiple-case-based investigation with semi-structured interviews and secondary data sources to create a context-rich insight to the area examined.FindingsThe findings indicate a strong orientation towards operational tools deployment aligned with financial management and resources and process planning, monitoring and control. Strategic perspectives of the respondents indicate an implicit, rather than explicit deployment of strategy tools and unstructured deployment, but general awareness of the resulting component issues. Clearer strategic approaches and strong implementation appear to positively influence success, when measured by growth.Research limitations/implicationsThis study is limited to nine organisations within a UK geographic region, and therefore, larger-scale investigation would be beneficial to extend and confirm the findings in differing contexts.Practical implicationsWith resource scarcity potentially stymying the opportunity for owner-managers to develop more structured approaches to strategic analysis and development, consideration should be given to how owner-managers can further develop their strategic thinking to support enhanced strategic outcomes for their organisations. Furthermore, strategy educationalists may wish to reflect upon the manner in which they prepare delegates for strategic roles, where the SME context may differ radically from corporate experience.Originality/valueThe methodology for this study differs substantially from previous investigations within the field, which has had relatively few contributions, as it uses in-depth, context-rich qualitative techniques to investigate the micro-processes at play. The conclusions capture new insights and indications and identify areas for further investigation, hence adding to the understanding of a complex and heterogeneous field.
Dryden v Johnson Matthey: The Boundaries of Actionable Damage
Authors: Huang Jarret J. 
Published: April 2019

AbstractIn Dryden v Johnson Matthey, the claimants sought to recover in tort for becoming sensitised to platinum salts by the defendant's negligence. The Supreme Court found, unanimously, that merely becoming sensitised, as opposed to developing an allergic reaction, sufficed as actionable damage. However, the court only provided two ‘indicative factors’ for when damage was ‘actionable’: whether there had been some impairment, and whether the effect of that impairment was ‘more than negligible’. This approach is unclear, in tension with other parts of the judgment, and produces undesirable broader consequences. It misses an opportunity for the Court to provide guidance on developments in tort like preventive damages, claimant‐specific loss, and the broader raison d'être of tort. A narrow and constrained adjustment to the law to permit recovery in negligence of pure economic loss for preventive damage could have achieved the same result without relying on somewhat convoluted mental gymnastics.
Contraception Care for Transmasculine Individuals on Testosterone Therapy
Authors: Boudreau Danielle , Mukerjee Ronica 
Published: April 2019

AbstractContraception and fertility‐associated advisement is needed for any individual with a uterus who is engaging in sexual activity with reproductive potential. As greater awareness spreads regarding the health care needs of transgender, nonbinary, and gender‐nonconforming individuals, the research on evidence‐based care for these populations lags behind. Many clinicians may not be well versed in the best practices to support the sexual and reproductive well‐being of individuals who are taking gender‐affirming hormone therapy. This article reviews the use of contraception for individuals who are on testosterone gender‐affirming hormone therapy. Each contraceptive method is individually considered for the risks and benefits that are unique to this population.
Gender Transition: The Moral Meaning of Bodily and Social Presentation
Authors: Watt Helen 
Published: April 2019

AbstractMedical and/or social gender transition need not involve denial of one's biological sex, but raises other taxing ethical issues. These range from sexual ethics issues narrowly understood to consideration of the claims of any spouse or children and indeed, of gender-discordant younger people who may follow one's example. As with intersex conditions, not all crossdressing or use of cross-sex hormones is excluded absolutely. Detransition, for example, could be rightly deferred for various reasons. However, as illustrated by the analogy of an infertile woman wanting to present as the pregnant mother of a child she plans to adopt, there is a significant social value in accurate bodily and other outward communication of one's actual/predominant sex (and occupancy of key allied roles).
Women’s and healthcare professionals’ views on immediate postnatal contraception provision: a literature review
Authors: Thwaites Annette , Tran Anh B , Mann Sue 
Published: April 2019

ObjectivesProvision of immediate postnatal contraception, including long-acting reversible contraceptive (LARC) methods, is increasingly identified and endorsed as a key strategy for reducing unplanned and rapid repeat pregnancies. This literature review aims to evaluatethe views of women and healthcare professionals regarding the receipt, initiation or delivery of these services.MethodsDatabases (Embase, Medline, CINAHL, HMIC) were searched for relevant English language studies, from January2003 to December 2017. In addition, Evidence Search, Google Scholar and Scopus (citation search) were used to identify further literature. Other relevant websites were accessed for policies, guidance and supplementary grey literature.ResultsThere is clear guidance on how to deliver good-quality postnatal contraception to women, but the reality of service delivery in the UK does not currently meet these aspirations, and guidance on implementation is lacking. The available evidence on the provision of immediate postnatal contraception focuses more on clinical rather than patient-centred outcomes. Research on postnatal women’s views is limited to receptivity to LARC and contraception counselling rather than what influences their decision-making process at this time. Research on views of healthcare professionals highlights a range of key systemic barriers to implementation.ConclusionsWhile views of postnatal women and healthcare professionals are largely in support of immediate postnatal contraception provision, important challenges have been raised and present a need for national sharing of service commissioning and delivery models, resources and evaluation data. Provider attitudes and training needs across multidisciplinary groups also need to be assessed and addressed as collaborative working across a motivated, skilled and up-to-date network of healthcare professionals is viewed as key to successful service implementation.
Bioelectrical impedance analysis does not detect an increase in total body water following isotonic fluid consumption
Authors: Matthews Evan L. , Hosick Peter A. 
Published: April 2019

Purpose: To determine if single-frequency foot-to-foot bioelectrical impedance analysis (BIA) can detect acute changes in total body water (TBW) following consumption of isotonic saline. All participants ate a sodium-free meal at 4 h prior to the data collection visit and had euhydration confirmed using urine specific gravity at the beginning of the experimental visit. Subjects drank 466 mL of isotonic saline (Na+ 140 mmol·L−1) following baseline measures. Blood sampling and BIA were performed at baseline and every 30 min for 3 h after saline consumption. Ten healthy participants completed this study. Plasma volume (5%Δ, p < 0.001) and serum sodium concentration (1%Δ, p < 0.001) increased by 60 min and 90 min, respectively. Body mass (p < 0.001) displayed a biphasic response increasing to a peak at 30 min (+0.38Δkg) and then decreasing to its minimum at 180 min (–0.35Δkg). BIA impedance (p = 0.678) was unaffected by the saline administration. BIA-derived TBW (p = 0.039) decreased from baseline starting at 150 min (0.21Δkg). Novelty Athletes and coaches wishing to achieve hyperhydration can do so through the consumption of isotonic fluid. 50 kHz foot-to-foot BIA-derived TBW is inadequate for measuring hyperhydration. Future studies should examine the physiological and performance effects of such a hyperhydration protocol.
THE ROLE OF INNOVATION METRICS IN INNOVATION SYSTEMS
Authors: ÖBERG CHRISTINA 
Published: April 2019

In innovation systems, venture firms, incubators and science parks may interact with universities to achieve commercialisable output. These various parties are connected to different guiding performance metrics — measures on each party’s performance — that influence their behaviours. This paper illustrates and discusses the role of performance metrics among various parties in innovation systems connected with early research ideas from universities. The empirical part of the paper is based on interviews with 20 researchers and 10 representatives of various innovation system organisations in an EU-based research project. The paper points out how parties in the innovation process saw different reasons to participate which were strongly connected with how each party was evaluated and which caused sub-optimisation in behaviours. Previous research on innovation systems has not focused on the rationales and behaviours of parties. The focus on metrics targets an important point for understanding innovation processes involving several parties and specifically doing so for support organisations that cannot be measured on revenues or profits.
Effect of assuming constant tissue scattering on measured tissue oxygenation values during tissue ischemia and vascular reperfusion
Authors: Hammer Shane M. , Hueber Dennis M. , Townsend Dana K. , Huckaby Lillie M. , Alexander Andrew M. , Didier Kaylin D. , Barstow Thomas J. 
Published: April 2019

The purpose of this study was to determine the effects of assuming constant tissue scattering properties on tissue oxygenation measurements during a vascular occlusion test (VOT). Twenty-one subjects (21.8 ± 1.9 yr) completed a VOT [1 min baseline (BL), 5 min of tissue ischemia (TI), and 3 min of vascular reperfusion (VR)]. Absolute concentrations of oxygenated heme (oxy-[heme]), deoxygenated heme (deoxy-[heme]), total heme (total [heme), tissue oxygen saturation (StO2), and heme difference [heme]diff) were measured using frequency domain near-infrared spectroscopy (FD-NIRS) while 1) continuously measuring and incorporating tissue scattering ([Formula: see text]) and 2) assuming scattering remained constant. FD-NIRS measured [Formula: see text] increased during TI at 692 nm ( P < 0.001) and decreased at 834 nm ( P < 0.001). During VR, [Formula: see text] decreased at 692 nm ( P < 0.001) and increased at 834 nm ( P < 0.001). When assuming constant scattering, oxy-[heme] was significantly less at TIpeak ( P < 0.05) while deoxy-[heme] and StO2 were significantly altered at BL, TIpeak, and VRpeak (all P < 0.001). Total [heme] did not change during the VOT. Absolute changes in deoxy-[heme], oxy-[heme], and StO2 in response to TI and VR were significantly exaggerated (all P < 0.001) and the rates of change during TI ( slope 1) and VR ( slope 2) in deoxy-[heme], oxy-[heme], StO2, and [heme]diff were significantly increased (all P < 0.05) when constant tissue scattering was assumed. These findings demonstrate the need for caution when interpreting NIRS data without continuously measuring tissue optical properties. Further, assuming tissue optical properties remain constant may have important consequences to experimental data and clinical conclusions made using NIRS. NEW & NOTEWORTHY NIRS measurements provide significant experimental and clinical insight. We demonstrate that absolute changes in tissue oxygenation measurements made with NIRS are overestimated and the kinetic responses of NIRS measurements are exaggerated by varying degrees among individuals if tissue scattering characteristics are assumed to remain constant during vascular occlusion tests.
The Degree of Multidimensional Severity of Alcohol Use Disorder among Treatment-Seeking Patients: Is There an Additive Effect of Parental Alcohol Use Disorder?
Authors: Ahmad-Nielsen Emil B. , Andersen Nicolai Gundtoft  , Andersen Kjeld , Nielsen Anette Søgaard , Mellentin Angelina I. 
Published: April 2019

<b><i>Background:</i></b> The additive effect of parental alcohol use disorders (AUD) is conventionally defined as an increasing risk of the offspring developing AUD relative to family history negative, &#x3c; family history positive with 1 parent (FHP1), &#x3c; FHP2. The few studies on the additive effect of parental AUD have focused on the risk of development of offspring AUD and not on the degree of multidimensional AUD addiction severity. <b><i>Aims:</i></b> The aims of the present study were to examine the frequency of treatment-seeking outpatients exposed to FHP1 and FHP2 and whether addiction severity was impacted by the additive effect of parental AUD among AUD female and male offspring. <b><i>Methods:</i></b> This cross-sectional study was based on 3,361 consecutive treatment-seeking outpatients from 2006 to 2016, assessed by means of the ­European Addiction Severity Index (EUROP-ASI). The ­EUROP-ASI assessed multidimensional addiction severity, comprising alcohol and other drug use, somatic and psychiatric health status, family and other social status, economy and employment-related problems and criminal status composite scores at treatment entry. <b><i>Results:</i></b> Among females, 40.38% had FHP1 and 15.68% FHP2, whereas males had 40.90% FHP1 and 13.24% FHP2. No conventional additive effect was found on the composite scores among both genders. However, another type of synergistic additive effect, only manifesting with exposure to FHP2, was found for employment-related problems and psychiatric status composite scores among male offspring. <b><i>Conclusions:</i></b> Exposure to parental AUD is strikingly high among treatment-seeking outpatients. Nonetheless, the additive effect has a modest impact on multidimensional addiction severity and is mostly related to psycho-social impairment among treatment-seeking male offspring.