bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iron Homeostasis Determines Fate of Human Pluripotent Stem Cells Via Glycerophospholipids-Epigenetic Circuit
Authors: Han Zhenbo , Yu Ying , Xu Juan , Bao Zhengyi , Xu Zihang , Hu Jiancheng , Yu Meixi , Bamba Djibril , Ma Wenya , Ding Fengzhi , Zhang Lai , Jin Mengyu , Yan Gege , Huang Qi , Wang Xiuxiu , Hua Bingjie , Yang Fan , Li Yuan , Lei Lei , Cao Nan , Pan Zhenwei , Cai Benzhi 
Published: January 2019

Abstract
Iron homeostasis is crucial for a variety of biological processes, but the biological role of iron homeostasis in pluripotent stem cells (PSCs) remains largely unknown. The present study aimed to determine whether iron homeostasis is involved in maintaining the pluripotency of human PSCs (hPSCs). We found that the intracellular depletion of iron leads to a rapid downregulation of NANOG and a dramatic decrease in the self-renewal of hPSCs as well as spontaneous and nonspecific differentiation. Moreover, long-term depletion of iron can result in the remarkable cell death of hPSCs via apoptosis and necrosis pathways. Additionally, we found that the depletion of iron increased the activity of lipoprotein-associated phospholipase A2 (LP-PLA2) and the production of lysophosphatidylcholine, thereby suppressing NANOG expression by enhancer of zeste homolog 2-mediated trimethylation of histone H3 lysine 27. Consistently, LP-PLA2 inhibition abrogated iron depletion-induced loss of pluripotency and differentiation. Altogether, the findings of our study demonstrates that iron homeostasis, acting through glycerophospholipid metabolic pathway, is essential for the pluripotency and survival of hPSCs. Stem Cells 2019;37:489–503
Chemoprevention with Somatuline© Delays the Progression of Pancreatic Neuroendocrine Neoplasms in a Mouse Model of Multiple Endocrine Neoplasia Type 1 (MEN1)
Authors: Lopez Caroline L. , Joos Barbara , Bartsch Detlef K. , Manoharan Jerena , Albers Max , Slater Emily P. , Bollmann Carmen , Roth Sylvia , Bayer Aninja , Fendrich Volker 
Published: January 2019

AbstractObjectiveLong‐acting synthetic somatostatin analogues (SSA) are an essential part of the treatment of neuroendocrine neoplasms. We evaluated the chemopreventive effects of a long‐acting somatostatin analogue on the development of pancreatic neuroendocrine neoplasms (pNENs) in a genetically engineered MEN1 knockout mouse model.Materials and methodsHeterozygote MEN1 knockout mice were injected every 28 days subcutaneously with the somatostatin analogue lanreotide (Somatuline Autogel©; Ipsen Pharma) or a placebo starting at day 35 after birth. Mice were euthanized after 6, 9, 12, 15 and 18 months, and the size and number of pNENs were measured due histological analysis and compared to the placebo group.ResultsThe median tumor size of pNENs was statistically significantly smaller after 9 (control group vs. SSA group; 706.476 µm2 vs. 195.271 µm2; p = 0.0012), 12 (placebo group vs. SSA group 822.022 vs. 255.482; p ≤ 0.001), 15 (placebo group vs. SSA group 1192.568 vs. 273.533; p ≤ 0.001) and after 18 months (placebo group vs. SSA group 1328.299 vs. 864.587; p ≤ 0.001) in the SSA group. Comparing the amount of tumors in both groups, a significant reduction was achieved in treated Men1(+/−) mice (41%, p = 0.002). Immunostaining showed, however, no significant difference in the expression of the apoptosis marker caspase‐3, but a significant difference in Ki67 index as a marker for tumor cell proliferation (p ≤ 0.005).ConclusionLong‐acting somatostatin analogues may be an effective chemopreventive approach to delay the progression of MEN1‐associated pNENs. After our preclinical results, we would recommend to evaluate the effects of long‐acting SSA in a prospective clinical trial.
Retrogression and Reaging Applied to Warm Forming of High-Strength Aluminum Alloy AA7075-T6 Sheet
Authors: Ivanoff Thomas A. , Carter Jon T. , Hector Louis G. , Taleff Eric M. 
Published: January 2019

Abstract
This study introduces retrogression forming, a new warm-forming methodology for high-strength aluminum alloys such as AA7075-T6. Retrogression forming combines a retrogression heat treatment with simultaneous warm forming at approximately 200 °C to improve upon the room-temperature ductility of AA7075-T6, approximately 10 pct in tension, and can then use the automotive paint-bake cycle to restore nearly peak-aged strength. Experimental data indicate that retrogression forming at 200 °C provides a tensile ductility of 20 pct, approximately double that of room temperature, and that subsequent reaging by a simulated paint bake restores hardness to within 10 pct of the original peak-aged (T6) hardness. To explore the retrogression-forming concept, the retrogression behaviors of two AA7075-T6 sheet materials from different suppliers are characterized between 200 °C and 350 °C. The times and temperatures of retrogression treatments suitable for simultaneous warm forming are determined, and tensile ductilities under these conditions are measured. Tensile ductilities during high-temperature deformation (up to 520 °C) are measured and compared to those possible under retrogression-forming conditions. Plastic flow at temperatures of 460 °C to 520 °C is governed by dislocation-climb-controlled creep, a mechanism different from the behaviors observed under retrogression-forming conditions.
Designing combinatorial exchanges for the reallocation of resource rights
Authors: Bichler Martin , Fux Vladimir , Goeree Jacob K. 
Published: January 2019

Significance
Overfishing is a prime environmental concern. Catch share systems have been shown to be effective tools to combat overfishing. But flawed initial allocations and the subsequent need for reallocation of catch shares often create challenging policy problems. Market-based solutions have attracted interest but the complex institutional and political constraints necessitate market forms to avoid undesirable outcomes. The combinatorial exchange we designed and implemented is a market design for the reallocation of catch shares. The design was adopted because it addressed stakeholders’ key requirements: fair pricing, avoiding fragmented share portfolios, and mitigating distortions from the introduction of catch shares via cost-effective and market-based subsidies.
Patched1–ArhGAP36–PKA–Inversin axis determines the ciliary translocation of Smoothened for Sonic Hedgehog pathway activation
Authors: Zhang Boyan , Zhuang Tenghan , Lin Qiaoyu , Yang Biying , Xu Xiaowei , Xin Guangwei , Zhu Shicong , Wang Gang , Yu Bin , Zhang Tingting , Jiang Qing , Zhang Chuanmao 
Published: January 2019

Significance
The ciliary membrane-localized transmembrane Hedgehog receptor Patched1 suppresses the ciliary translocation of the transmembrane oncoprotein Smoothened and consequently Hedgehog pathway activation, but the mechanism underlying this process remains largely unknown. Here, we show that the Patched1–ArhGAP36–PKA–Inversin–Smoothened axis determines this process. We uncover that the ciliary translocation of Smoothened depends on its interaction with phosphorylated ciliary Inversin, which is sequentially achieved by the removal of centrosomal ArhGAP36 with ciliary Patched1 and the accumulation of centrosomal PKA during Hedgehog pathway activation. Our findings reveal how the Hedgehog pathway is spontaneously activated in tumor cells carrying loss-of-function mutations of Patched1 or oncogenic mutations of Smoothened.
Secondary magnetite in ancient zircon precludes analysis of a Hadean geodynamo
Authors: Tang Fengzai , Taylor Richard J. M. , Einsle Josh F. , Borlina Cauê S. , Fu Roger R. , Weiss Benjamin P. , Williams Helen M. , Williams Wyn , Nagy Lesleis , Midgley Paul A. , Lima Eduardo A. , Bell Elizabeth A. , Harrison T. Mark , Alexander Ellen W. , Harrison Richard J. 
Published: January 2019

Significance
The Earth’s geodynamo is critical in protecting our atmosphere, and thus plays an important role in the habitability of our planet. As such, the Earth’s magnetic field has likely played a crucial role in the emergence of life around 4 billion years ago during the Hadean–Archean Eons. However, we know little about the behavior of the geodynamo during this critical period. Recent efforts have focused on the magnetic signals harbored by Jack Hills zircon crystals, the oldest terrestrial material. Here we show the magnetic carriers in such grains. Our results demonstrate that although ancient zircon grains may contain ideal magnetic recorders, they do not record the magnetic field strength at the time of zircon growth.
Early patterns of skill acquisition and immigrants’ specialization in STEM careers
Authors: Rangel Marcos A. , Shi Ying 
Published: January 2019

Significance
Do net returns to early investments in skill acquisition explain patterns of occupational specialization among immigrants? We design an empirical analysis of nationally representative data to show that age at immigration and mother tongue influence course-taking patterns in high school and college major choice. Immigrant children with greater relative endowments in nonlanguage skills specialize in math and science course credits over English and are more likely to pursue science-, technology-, engineering-, and math-intensive subjects in college. This reveals the early influence of comparative advantage over immigrant career choices and economic assimilation in the United States.
Global-scale dispersal and connectivity in mangroves
Authors: Van der Stocken Tom , Carroll Dustin , Menemenlis Dimitris , Simard Marc , Koedam Nico 
Published: January 2019

Significance
Mangroves are of considerable ecological and socioeconomical importance; however, substantial areal losses have been recorded in many regions, driven primarily by anthropogenic disturbances and sea level rise. Oceanic dispersal of mangrove propagules provides a key mechanism for shifting distributions in response to environmental change. Here we provide a model framework for describing global dispersal and connectivity in mangroves. We identify important dispersal routes, barriers, and stepping-stones and quantify the influence of minimum and maximum floating periods on simulated connectivity patterns. Our study provides a baseline to improve our understanding of observed mangrove species distributions and, in combination with climate data, the expected range shifts under climate change.
Thermal disequilibration of ions and electrons by collisionless plasma turbulence
Authors: Kawazura Yohei , Barnes Michael , Schekochihin Alexander A. 
Published: January 2019

Significance
Large-scale astrophysical processes inject energy into turbulent motions and electromagnetic fields, which carry this energy to small scales and eventually thermalize it. How this energy is partitioned between ions and electrons is important both in plasma physics and in astrophysics. Here we determine this energy partition via gyrokinetic turbulence simulations and provide a simple prescription for the ion-to-electron heating ratio. We find that turbulence promotes disequilibration of the species: When magnetic energy density is greater than the thermal energy density, electrons are preferentially heated, whereas when it is smaller, ions are. This is a relatively rare example of nature promoting an ever more out-of-equilibrium state in an environment where particle collisions are not frequent enough to equalize the temperatures of the species.
Analysis of research intensity on infectious disease by disease burden reveals which infectious diseases are neglected by researchers
Authors: Furuse Yuki 
Published: January 2019

Significance
Threats from emerging and reemerging infectious diseases have increased globally. However, neglected tropical diseases, such as Chagas disease and schistosomiasis, are believed to attract low attention. We investigated which infectious diseases have been neglected by researchers and which have received attention through an analysis of disease burden and research activity. We found, for example, that influenza and HIV/AIDS have attracted high research attention in relation to their disease burden, while paratyphoid fever has attracted low attention considering the disease burden. Interestingly, not all so-called neglected tropical diseases were subject to low research intensity. Further discussion must occur with regard to the appropriate allocation of resources for research into infectious diseases.
Herpes simplex virus 1 ICP8 mutant lacking annealing activity is deficient for viral DNA replication
Authors: Weerasooriya Savithri , DiScipio Katherine A. , Darwish Anthar S. , Bai Ping , Weller Sandra K. 
Published: January 2019

Significance
Herpes simplex virus (HSV) is a ubiquitous human pathogen. The mechanism of HSV DNA replication is poorly understood. ICP8, the multifunctional HSV single-strand DNA binding protein (SSB), is essential for viral growth and DNA replication. ICP8 is also capable of efficiently annealing complementary ssDNA and has been classified as a single-strand annealing protein (SSAP); however, the role of annealing during infection is still unclear. In this paper, we characterize a mutant of ICP8 that retains many of its functions as a replicative SSB but lacks annealing activity. We show that ICP8 annealing activity is essential for viral DNA replication. These findings support our hypothesis that HSV-1 uses recombination-dependent mechanisms to replicate its DNA.
Mcm10 has potent strand-annealing activity and limits translocase-mediated fork regression
Authors: Mayle Ryan , Langston Lance , Molloy Kelly R. , Zhang Dan , Chait Brian T. , O’Donnell Michael E. 
Published: January 2019

Significance
Fork regression is a way of circumventing or dealing with DNA lesions and is important to genome integrity. Fork regression is performed by double-strand DNA ATPases that initially cause newly synthesized strands to unpair from the parental strands, followed by pairing of the new strands and reversal of the fork. This study shows that Mcm10, an essential replication factor, efficiently anneals complementary strands and also inhibits fork regression by SMARCAL1. Moreover, the study localizes the Mcm10 DNA-binding domain to the N-terminal domains of the replicative CMG helicase at the forked nexus. Thus, forks that are unimpeded would contain Mcm10 at a strategic position where its DNA-binding and/or annealing function may block fork regression enzymes and thereby protect active forks from becoming reversed.
Transthoracic clamp versus endoaortic balloon occlusion in minimally invasive mitral valve surgery: a systematic review and meta-analysis
Authors: Rival Paul Martin , Moore Theresa H M , McAleenan Alexandra , Hamilton Hamish , Du Toit Zachary , Akowuah Enoch , Angelini Gianni D , Vohra Hunaid A 
Published: January 2019

Summary

This systematic review and meta-analysis aims to determine outcomes following aortic occlusion with the transthoracic clamp (TTC) versus endoaortic balloon occlusion (EABO) in patients undergoing minimally invasive mitral valve surgery. A subgroup analysis compares TTC to EABO with femoral cannulation separately from EABO with aortic cannulation. We searched Medline and Embase up to December 2018. Two people independently and in duplicate screened title and abstracts, full-text reports, extracted data and assessed the risk of bias using the Cochrane risk-of-bias tool for non-randomized studies. We identified 1564 reports from which 11 observational studies with 4181 participants met the inclusion criteria. We found no evidence of difference in the risk of postoperative death or cerebrovascular accident (CVA) between the 2 techniques. Evidence for a reduction in aortic dissection with TTC was found: 4 of 1590 for the TTC group vs 19 of 2492 for the EABO group [risk ratio 0.33, 95% confidence interval (CI) 0.12–0.93; P = 0.04]. There was no difference in aortic cross-clamp (AoX) time between TTC and EABO [mean difference (MD) −5.17 min, 95% CI −12.40 to 2.06; P = 0.16]. TTC was associated with a shorter AoX time compared to EABO with femoral cannulation (MD −9.26 min, 95% CI −17.00 to −1.52; P = 0.02). EABO with aortic cannulation was associated with a shorter AoX time compared to TTC (MD 7.77 min, 95% CI 3.29–12.26; P &lt; 0.001). There was no difference in cardiopulmonary bypass (CPB) time between TTC and EABO with aortic cannulation (MD −4.98 min, 95% CI −14.41 to 4.45; P = 0.3). TTC was associated with a shorter CPB time compared to EABO with femoral cannulation (MD −10.08 min, 95% CI −19.93 to −0.22; P = 0.05). Despite a higher risk of aortic dissection with EABO, the rates of survival and cerebrovascular accident across the 2 techniques are similar in minimally invasive mitral valve surgery.
A Scoping Review of Literature on Sex and Gender Differences Among Dementia Spousal Caregivers
Authors: Arbel Ifah , Bingham Kathleen S , Dawson Deirdre R 
Published: January 2019

Abstract

Background and Objectives
Sex and gender differences among dementia spousal caregivers have been investigated, but never systematically reviewed or synthesized. A synthesis of findings can help facilitate specificity in practice and in health policy development. As a first step towards such a synthesis, this scoping review reports the available evidence, identifies research gaps, and suggests possible directions for future research.

Research Design and Methods
A scoping review methodology was used to identify articles, and to chart and analyze data. Systematic searches for published, empirical studies, with an explicit goal or hypothesis related to sex or gender differences were conducted in seven databases.

Results
Sixty-one studies met inclusion criteria. Most (n = 45) were quantitative, cross-sectional studies. Caregivers included in the studies were generally 61–70 years old, Caucasian, middle-class, and highly educated. The most extensively investigated differences are: depression, burden, objective physical health, and informal supports.

Discussion and Implications
This scoping review is the first to summarize and critique the research on sex and gender differences that are specific to dementia spousal caregivers. The review can be used by researchers to make decisions regarding future systematic reviews and primary studies. To further strengthen the evidence base, future studies may benefit from including more caregivers of ethnic minorities, using more qualitative, longitudinal, or experimental designs, and focusing on variables needed to inform caregiving models and theories. Overall, this scoping review contributes to furthering gender-sensitive practices and policies that are better tailored to the specific needs of this population.
A network-based integrated framework for predicting virus-host interactions
Authors: Wang Weili , Ren Jie , Tang Kujin , Dart Emily , Ignacio-Espinoza Julio Cesar , Fuhrman Jed A. , Braun Jonathan , Sun Fengzhu , Ahlgren Nathan A. 
Published: January 2019

AbstractMetagenomic sequencing has greatly enhanced the discovery of viral genomic sequences; however it remains challenging to identify the host(s) of these new viruses. We developed VirHostMatcher-Net, a flexible, network-based, Markov random field framework for predicting virus-host interactions using multiple, integrated features: CRISPR sequences, sequence homology, and alignment-free similarity measures (and WIsH). Evaluation of this method on a benchmark set of 1,075 known viruses-host pairs yielded host prediction accuracy of 62% and 85% at the genus and phylum levels, representing 12-27% and 10-18% improvement respectively over previous single-feature prediction approaches. We applied our host-prediction tool to three metagenomic virus datasets: human gut crAss-like phages, marine viruses, and viruses recovered from globally-distributed, diverse habitats. Host predictions were frequently consistent with those of previous studies, but more importantly, this new tool made many more confident predictions than previous tools, up to 6-fold more (n>60,000), greatly expanding the diversity of known virus-host interactions.
FinDonor 10 000 study: A cohort to identify iron depletion and factors affecting it in Finnish blood donors
Authors: Partanen Jukka , Niittymäki Pia , Nikiforow Nina , Palokangas Elina , Lobier Muriel , Larjo Antti , Mattila Pirkko , Castrén Johanna , Arvas Mikko 
Published: January 2019

AbstractBackground and ObjectivesThere is increasing evidence that frequent blood donation depletes the iron stores of some blood donors. The FinDonor 10 000 study was set up to study iron status and factors affecting iron stores in Finnish blood donors. In Finland, iron supplementation for at-risk groups has been in place since the 1980’s.Material and Methods2584 blood donors (N= 8003 samples) were recruited into the study alongside the standard donation at three donation sites in the capital region of Finland between 5/2015 and 12/2017. All participants were asked to fill out a questionnaire about their health and lifestyle. Blood samples were collected from the sample pouch of whole blood collection set, kept in cool temperature and processed centrally. Whole blood count, CRP, ferritin and sTFR were measured from the samples and DNA was isolated for GWAS studies.ResultsParticipant demographics, albeit in general similar to the general blood donor population in Finland, indicated some bias toward older and more frequent donors. Participation in the study increased median donation frequency of the donors. Analysis of the effect of time lag from the sampling to the analysis and the time of day when sample was drawn revealed small but significant time-dependent changes.ConclusionThe FinDonor cohort now provides us with tools to identify potential donor groups at increased risk of iron deficiency as factors explaining this risk. The increase in donation frequency during the study suggests that scientific projects can be used to increase the commitment of blood donors.
Detection of circulating extracellular mRNAs by modified small RNA-sequencing analysis
Authors: Akat Kemal M. , Lee Youngmin A. , Hurley Arlene , Morozov Pavel , Max Klaas E.A. , Brown Miguel , Bogardus Kimberly , Sopeyin Anuoluwapo , Hildner Kai , Diacovo Thomas , Neurath Markus F. , Borggrefe Martin , Tuschl Thomas 
Published: January 2019

AbstractExtracellular mRNAs (ex-mRNAs) potentially supersede extracellular miRNAs (ex-miRNAs) and other RNA classes as biomarkers. Here, we present a comprehensive extracellular RNA (exRNA) study in human blood circulation based on conventional small RNA-sequencing (sRNA-seq) and sRNA-seq after T4 polynucleotide kinase (PNK) end-treatment of total exRNA isolated from serum and platelet-poor EDTA, ACD, and heparin plasma. Applying strict criteria for read mapping and annotation, we found that compared to conventional sRNA-seq PNK-treatment increased the detection of informative ex-mRNAs reads up to 50-fold. Based on captured ex-mRNAs from healthy individuals, we concluded that the exRNA pool is dominated by hematopoietic cells and platelets, with additional contribution from the liver. About 60% of the 15- to 42-nt long reads originated from the coding sequences, in a pattern reminiscent of ribosome-profiling studies for high abundance transcripts. Blood sample type had a considerable influence on the exRNA profile. The number of detected distinct ex-mRNA transcripts ranged from on average ~350 to 1100 in the different plasma types. In serum, additional transcripts from neutrophils and hematopoietic cells increased this number to ~2300. For EDTA and ACD, in particular, we found evidence of destabilization of mRNA and non-coding RNA ribonucleoprotein complexes. In a proof-of-concept study, we compared patients with acute coronary syndrome (ACS) to healthy controls. The improved tissue resolution of ex-mRNAs after PNK-treatment enabled us to detect a neutrophil-signature in ACS that escaped detection in an ex-miRNA analysis. Thus, ex-mRNAs provide superior resolution for the study of exRNA changes in vivo and ex vivo. They can be readily studied by sRNA-seq after T4 PNK end-treatment.