bluuebunny/crossref_metadata_2025_split huggingface dataset:
ApoE e2 and aging-related outcomes in 379,000 UK Biobank participants
Authors: Kuo Chia-Ling , Pilling Luke C. , Atkins Janice L. , Kuchel George A. , Melzer David 
Published: February 2020

AbstractThe Apolipoprotein E (APOE) e4 allele is associated with reduced longevity and increased Coronary Artery Disease (CAD) and Alzheimer’s disease, with e4e4 having markedly larger effect sizes than e3e4. The e2 longevity promoting variant is less studied. We conducted a phenome-wide association study of ApoE e2e3 and e2e2 with aging phenotypes, to assess their potential as targets for anti-aging interventions. Data were from 379,000 UK Biobank participants, aged 40 to 70 years. e2e3 (n=46,535) had mostly lower lipid-related biomarker levels including reduced total and LDL-cholesterol, and lower risks of CAD (Odds Ratio=0.87, 95% CI: 0.83 to 0.90, p=4.92×10−14) and hypertension(OR=0.94, 95% CI: 0.92 to 0.97, p=7.28×10−7) versus e3e3. However, lipid changes in e2e2 (n=2,398) were more extreme, including a marked increase in triglyceride levels (0.41 Standard Deviations, 95% CI: 0.37 to 0.45, p=5.42×10−92), with no associated changes in CAD risks. There were no associations with biomarkers of kidney function. The effects of both e2e2 and e2e3 were minimal on falls, muscle mass, grip strength or frailty. In conclusion, e2e3 has protective effects on some health outcomes, but the effects of e2e2 are not similar, complicating the potential usefulness of e2 as a target for anti-aging intervention.
Epigenomic translocation of H3K4me3 broad domains over oncogenes following hijacking of super-enhancers
Authors: Mikulasova Aneta , Kent Daniel , Trevisan-Herraz Marco , Karataraki Nefeli , Fung Kent T.M. , Ashby Cody , Cieslak Agata , Yaccoby Shmuel , van Rhee Frits , Zangari Maurizio , Thanendrarajan Sharmilan , Schinke Carolina , Morgan Gareth J. , Asnafi Vahid , Spicuglia Salvatore , Brackley Chris A. , Corcoran Anne E. , Hambleton Sophie , Walker Brian A. , Rico Daniel , Russell Lisa J. 
Published: February 2020

AbstractChromosomal translocations are important drivers of haematological malignancies whereby proto-oncogenes are activated by juxtaposition with enhancers, often calledenhancer hijacking. We analysed the epigenomic consequences of rearrangements between the super-enhancers of the immunoglobulin heavy locus (IGH)and proto-oncogeneCCND1that are common in B-cell malignancies. By integrating BLUEPRINT epigenomic data with DNA breakpoint detection, we characterised the normal chromatin landscape of the humanIGHlocus and its dynamics after pathological genomic rearrangement. We detected an H3K4me3 broad domain (BD) within theIGHlocus of healthy B cells that was absent in samples withIGH-CCND1translocations. The appearance of H3K4me3-BD overCCND1in the latter was associated with overexpression and extensive chromatin accessibility of its gene body. We observed similar cancer-specific H3K4me3-BDs associated with hijacking of super-enhancers of other common oncogenes in B-cell (MAF,MYCandFGFR3/NSD2) and T-cell malignancies (LMO2, TLX3andTAL1). Our analysis suggests that H3K4me3-BDs can be created by super-enhancers and supports the new concept ofepigenomic translocation, where the relocation of H3K4me3-BDs from cell identity genes to oncogenes accompanies the translocation of super-enhancers.
Regulated unbinding of ZAP70 at the T cell receptor by kinetic avidity
Authors: Goyette Jesse , Depoil David , Yang Zhengmin , Isaacson Samuel A. , Allard Jun , van der Merwe P. Anton , Gaus Katharina , Dustin Michael L , Dushek Omer 
Published: February 2020

AbstractProtein-protein binding domains are critical in signalling networks. Src homology 2 (SH2) domains are binding domains that interact with sequences containing phosphorylated tyrosines. A subset of SH2 domain-containing proteins have tandem domains, which are thought to enhance binding affinity and specificity. However, a trade-off exists between long-lived binding and the ability to rapidly reverse signalling, which is a critical requirement of noise filtering mechanisms such as kinetic proofreading. Here, we use modelling to show that the unbinding rate of tandem, but not single, SH2 domains can be accelerated by phosphatases when tandem domains bind by a kinetic, but not a static, avidity mode. We use surface plasmon resonance to show that ZAP70, a tandem SH2 domain-containing kinase, binds kinetically to biphosphorylated peptides from the T cell antigen receptor (TCR) and that the unbinding rate can be accelerated by the phosphatase CD45. An important functional prediction of regulated unbinding is that the intracellular ZAP70/TCR half-life in T cells will be correlated to the extracellular TCR/antigen half-life and we show that this is the case in both cell lines and primary T cells. The work highlights that binding by kinetic avidity breaks the trade-off between signal fidelity (requiring long half-life) and signal reversibility (requiring short half-life), which is a key requirement for T cell antigen discriminated mediated by kinetic proofreading.
The irradiated brain microenvironment supports glioma stemness and survival via astrocyte-derived Transglutaminase 2
Authors: Berg Tracy J. , Marques Carolina , Pantazopoulou Vasiliki , Johansson Elinn , von Stedingk Kristoffer , Lindgren David , Pietras Elin J. , Bergström Tobias , Swartling Fredrik J. , Governa Valeria , Bengzon Johan , Belting Mattias , Axelson Håkan , Squatrito Massimo , Pietras Alexander 
Published: February 2020

AbstractThe tumor microenvironment plays an essential role in supporting glioma stemness and radioresistance, and following radiotherapy, recurrent gliomas form in an irradiated microenvironment. Here, we found that astrocytes, when pre-irradiated, increased stemness and survival of co-cultured glioma cells. Tumor-naïve brains increased reactive astrocytes in response to radiation, and mice subjected to radiation prior to implantation of glioma cells developed more aggressive tumors. We identified extracellular matrix derived from irradiated astrocytes as a major driver of this phenotype, and astrocyte-derived transglutaminase 2 (TGM2) as a promoter of glioma stemness and radioresistance. TGM2 levels were increased after radiation in vivo and in recurrent human glioma, and TGM2 inhibitors abrogated glioma stemness and survival. These data suggest that irradiation of the brain results in the formation of a tumor-supportive microenvironment. Therapeutic targeting of radiation-induced, astrocyte-derived extracellular matrix proteins may enhance the efficacy of standard of care radiotherapy by reducing stemness in glioma.
A screening of the MMV Pathogen Box® reveals new potential antifungal drugs against the etiologic agents of chromoblastomycosis
Authors: Coelho Rowena Alves , Joffe Luna Sobrino , Alves Gabriela Machado , Figueiredo-Carvalho Maria Helena Galdino , Brito-Santos Fábio , Amaral Ana Claudia Fernandes , Rodrigues Marcio L. , Almeida-Paes Rodrigo 
Published: February 2020

AbstractChromoblastomycosis (CBM) is a chronic subcutaneous mycosis caused by traumatic implantation of many species of black fungi. Due to the refractoriness of some cases and common recurrence of CBM, a more effective and less time-consuming treatment is mandatory. The aim of this study was to identify compounds within vitroantifungal activity in the Pathogen Box® compound collection against different CBM agents. Synergism of these compounds with drugs currently used to treat CBM was also assessed. An initial screening of the drugs present in this collection at 1μM was performed with aFonsecaea pedrosoiclinical strain according to the EUCAST protocol. The compounds with activity against this fungus were also tested against other seven etiologic agents of CBM (Cladophialophora carrionii,Phialophora verrucosa,Exophiala jeanselmei,Exophiala dermatitidis,Fonsecaea monophora,Fonsecaea nubica, andRhinocladiella similis) at concentrations ranging from 0.039 to 10 μM. The analysis of potential synergism of these compounds with itraconazole and terbinafine was performed by the checkerboard method. Eight compounds inhibited more than 60% of theF. pedrosoigrowth: difenoconazole, bitertanol, iodoquinol, azoxytrobin, MMV688179, MMV021013, trifloxystrobin, and auranofin. Iodoquinol produced the lowest MIC values (1.25 - 2.5μM) and MMV688179 showed MICs that were higher than all compounds tested (5 - >10μM). When auranofin and itraconazole were tested in combination, a synergistic interaction (FICI = 0.37) was observed against theC. carrioniiisolate. In summary, auranofin, iodoquinol, and MMV021013 were identified as promising compounds to be tested in CBM models of infection.
Thousands of novel unannotated proteins expand the MHC I immunopeptidome in cancer
Authors: Ouspenskaia Tamara , Law Travis , Clauser Karl R. , Klaeger Susan , Sarkizova Siranush , Aguet François , Li Bo , Christian Elena , Knisbacher Binyamin A. , Le Phuong M. , Hartigan Christina R. , Keshishian Hasmik , Apffel Annie , Oliveira Giacomo , Zhang Wandi , Chow Yuen Ting , Ji Zhe , Jungreis Irwin , Shukla Sachet A. , Bachireddy Pavan , Kellis Manolis , Getz Gad , Hacohen Nir , Keskin Derin B. , Carr Steven A. , Wu Catherine J. , Regev Aviv 
Published: February 2020

AbstractTumor epitopes – peptides that are presented on surface-bound MHC I proteins - provide targets for cancer immunotherapy and have been identified extensively in the annotated protein-coding regions of the genome. Motivated by the recent discovery of translated novel unannotated open reading frames (nuORFs) using ribosome profiling (Ribo-seq), we hypothesized that cancer-associated processes could generate nuORFs that can serve as a new source of tumor antigens that harbor somatic mutations or show tumor-specific expression. To identify cancer-specific nuORFs, we generated Ribo-seq profiles for 29 malignant and healthy samples, developed a sensitive analytic approach for hierarchical ORF prediction, and constructed a high-confidence database of translated nuORFs across tissues. Peptides from 3,555 unique translated nuORFs were presented on MHC I, based on analysis of an extensive dataset of MHC I-bound peptides detected by mass spectrometry, with >20-fold more nuORF peptides detected in the MHC I immunopeptidomes compared to whole proteomes. We further detected somatic mutations in nuORFs of cancer samples and identified nuORFs with tumor-specific translation in melanoma, chronic lymphocytic leukemia and glioblastoma. NuORFs thus expand the pool of MHC I-presented, tumor-specific peptides, targetable by immunotherapies.
Protein interaction mapping reveals widespread targeting of development-related host transcription factors by phytoplasma effectors
Authors: Marrero Miguel Correa , Capdevielle Sylvain , Huang Weijie , Al-Subhi Ali M. , Busscher Marco , Busscher-Lange Jacqueline , van der Wal Froukje , de Ridder Dick , van Dijk Aalt D.J. , Hogenhout Saskia A. , Immink Richard G.H. 
Published: February 2020

AbstractPhytoplasmas are pathogenic bacteria that reprogram plant host development for their own benefit. Previous studies have characterized a few different phytoplasma effector proteins that destabilize specific plant transcription factors. However, these are only a small fraction of the potential effectors used by phytoplasmas; therefore, the molecular mechanisms through which phytoplasmas modulate their hosts require further investigation. To obtain further insights into the phytoplasma infection mechanisms, we generated a protein-protein interaction network between a broad set of phytoplasma effectors and a large, unbiased collection ofArabidopsis thalianatranscription factors and transcriptional regulators. We found widespread, but specific, interactions between phytoplasma effectors and host transcription factors, especially those related to host developmental processes. In particular, many unrelated effectors target specific sets of TCP transcription factors, which regulate plant development and immunity. Comparison with other host-pathogen protein interaction networks shows that phytoplasma effectors have unusual targets, indicating that phytoplasmas have evolved a unique and unusual infection strategy. This study contributes a rich and solid data source that guides further investigations of the functions of individual effectors, as demonstrated for some herein. Moreover, the dataset provides insights into the underlying molecular mechanisms of phytoplasma infection.
Estimation of the equivalent tourist population trough indirect methods
Authors: Fernández Melchor , Lazovski Oleg 
Published: February 2020

Purpose
This proposal represents four main advantages: the immediate availability of the relevant information to the local manager; its potential application to any municipality regardless of its size; its reduced economic cost both in terms of information and calculation; and the possibility of obtaining information for very short periods (monthly or even daily) which is very important in areas where the population varies significantly throughout the year.

Design/methodology/approach
The authors present an indirect estimation method based on extrapolating the equivalent tourist population from the monthly variations in the production of solid urban waste.

Findings
It would also be desirable to compare the estimates made by using other indirect indicators such as electricity or water consumption, which could also provide relevant information on the degree of use of second homes.

Originality/value
These advantages turn this indicator into a practical and accessible estimation tool, which can be directly applied to the planning and management of all types of services and facilities provided by municipalities.
Paleoearthquake Investigation along the Chenghai Fault Zone since ∼500 ka, Southeast Margin of the Tibetan Plateau
Authors: YANG Shuaibin , QIAO Yansong , WU Zhonghai , ZHANG Xujiao , QI Lin , HE Zexin , LIANG Ying 
Published: February 2020

AbstractThe Chenghai fault zone is located in the Sichuan–Yunnan rhombus block, which is surrounded by the Honghe River, Xianshuihe–Xiaojiang, and Jinsha River fault zones. As a mid‐continental active fault, it is one of the most important seismogenic fractures in the southeast margin of the Tibetan Plateau. Geological seismic study is an important supplement to the historical seismic record; therefore, identification of paleoearthquake events in this region is of great significance to reveal the pattern and mechanism of earthquake development. In this study, detailed investigation has been carried out on the earthquake traces that formed in the Quaternary sediments in the Jinsha River section of the Chenghai fault zone, and samples for dating chronology testing were also collected. Many paleoearthquake traces were discovered in the field, including earthquake fissions, dammed lake sediments and landslides, earthquake‐generated rock falls, seismic faults, and sand liquefaction veins. The collected samples were tested using optically stimulated luminescence, electron‐spin resonance, and U‐series methods. A total of 68 chronological samples were dated, combined with the results of field investigations, and 10 large paleoearthquake events were discovered in this region since 500 ka, which are at approximately 450, 400, 345, 300, 250, 190, 155, 105, 75, and 25 ka. Ten tectonic activity periods that produced multiple paleoearthquake events were identified since 500 ka. This study identifies paleoearthquake events in longer scales, larger spaces, and more extensive sediments, which provides new perspectives and new ideas for paleoearthquake research.
Phenological stages ofMediterraneanforage legumes, based on the BBCH scale
Authors: Enriquez‐Hidalgo Daniel , Cruz Trinidad , Teixeira Dayane L. , Steinfort Ursula 
Published: February 2020

AbstractOne of the most widespread methodologies used to describe phenological stages in plants was developed by the Biologische Bundesanstalt Bundessortenamt und Chemische Industrie (BBCH). The BBCH scale utilises a decimal‐code system that divides plant phenological stages into a binary code composed of the principal and the secondary stages. This system has been extensively used to describe the phenological stages of diverse species, but there is no phenological description that can aid researchers in defining the duration of phenological stages of annual Mediterranean forage legumes that present different growth habits. The development of a precise phenological scale for forages enables the determination of grazing management strategies to attain a desired forage yield and quality as to precisely define the timing of agronomical practices. We have adapted the BBCH decimal‐code scale forMedicago polymorpha,Trifolium alexandrinum,Trifolium subterraneum, andVicia benghalensis. The scale consists of 10 main stages with specific secondary stages. Descriptive keys with illustrations will help identify any particular phenological stage for each species. The scales presented here will aid researchers and the agricultural community in clearly defining the timing of agronomical practices, such as the appropriate time for grazing/harvest of these species.
The effect of the pine woolly aphid (Pineus pini) on survival, growth and natural selection in Scots pine (Pinus sylvestris) in Iceland
Authors: Heiðarsson Lárus , Sigurdsson Bjarni D. , Davíðsson Benjamín Ö. , Hrafnkelsdóttir Brynja , Sigurgeirsson Aðalsteinn , Skúlason Brynjar , D. Vest María , Halldorsson Guðmundur 
Published: February 2020

Abstract
Scots pine Pinus sylvestris was originally introduced to Iceland in the beginning of the 20th Century. Extensive plantings started in the late 1940s and, in total, 2–3 million Scots pine seedlings were planted, mainly originating from two counties in northern Norway. Part of this plant material was imported as seedlings.
Pine woolly aphid Pineus pini was introduced to Iceland before 1940, most likely on imported seedlings in 1937.
High mortality of Scots pine, concurrent with high infestation of the pine woolly aphid, was observed in Iceland during the late 1950s and 1960s and planting was discontinued.
Provenance trials with Scots pine were established in Iceland in 2004–2006. They consisted of 15 provenances from Norway, four from Finland, four from Scotland, one from Russia, one from the Austrian Alps and three first generation Scots pine provenances from Iceland, collected from survivors of the epidemic in the 1950s and 1960s. In total, there were 28 provenances.
The Icelandic provenances had significantly lower P. pini infestation than all the provenances of non‐Icelandic origin, which indicates that natural selection in Scots pine in Iceland has occurred in favour of individuals less susceptible to P. pini.
Reporting assisted reproductive technology success rates on Australian and New Zealand fertility clinic websites
Authors: Goodman Lucy Kate , Prentice Lucy Rebecca , Chanati Rebecca , Farquhar Cynthia 
Published: February 2020

BackgroundFertility clinics commonly report their success rates online. These can be difficult to interpret as they are influenced by the way the data are presented. To improve transparency, the Reproductive Technology Accreditation Committee (RTAC) has published guidelines to support fertility clinics with their online reporting of success rates. However, it is unclear whether compliance with these guidelines will allow patients to make fair comparisons between clinics.AimsTo illustrate the variability in patient and treatment populations that contribute to fertility clinic published rates.Materials and MethodsFertility clinics offering in vitro fertilisation treatment in Australia or New Zealand were assessed for compliance with six guidelines adapted from RTAC’s code of practice, for reporting success rates in the public domain. All graphs and/or tables reporting clinic success rates were assessed to illustrate the combination of outcome or treatment variables contributing to each dataset.ResultsTwenty of the 30 fertility clinic websites reported success rates. Of these only 17 reported live births. The median compliance score with RTAC guidelines was 8/8 (interquartile range: 6–8). Of 41 figures published across all websites, five reported clinical pregnancy rates as their only outcome measure. Thirty‐seven figures reported success rates ‘per embryo transfer’, two figures used ‘per egg collection’, and no figures described success rates ‘per cycle started’. Thirty‐two different combinations of reporting variables were observed.ConclusionsWebsites were broadly compliant with RTAC’s guidelines. However, considering the variability in patient and treatment groups contributing to success rate data, patients cannot be expected to make an informed decision based on clinics’ self‐reported outcomes. RTAC guidelines could be improved by providing a clear definition of success, including the appropriate use of denominators.
Allostasis and Adaptation: Biocultural Processes Integrating Lifestyle, Life History, and Blood Pressure Variation
Authors: James Gary D. 
Published: February 2020

ABSTRACTAllostasis (literally “stability through change”) is a key concept for understanding how human behavior and physiological adaptation are related. The continuous variation in arterial blood pressure is an exemplar of allostasis. The purpose of this article is to describe theoretical and methodological developments that have led to an improved biocultural understanding of arterial blood pressure responses to everyday life in humans using allostasis as a paradigm. Arterial pressure variation is directly related to lifestyle, or more specifically, the things that people do, think, and experience in their daily lives. Allostatic patterns of arterial pressure variation also change with life‐history events. Patterns are altered as people age and take on differing social roles, and patterns vary between men and women. The cumulative effects of allostasis is the development of allostatic load, or a “wearing out” of the system. Studies have linked allostatic load to the development of cardiovascular diseases (CVD). However, the rate and trajectory of allostatic load through adult life is effectively dictated by developmental and evolutionary processes that impact allostasis and will vary among populations as a consequence of developmental, heritable, environmental, and cultural differences. Allostasis is the paradigm for biocultural studies of arterial blood pressure. [allostasis, adaptation, blood pressure, life history, biocultural]