bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neonatal infection leads to increased susceptibility to Aβ oligomer-induced brain inflammation, synapse loss and cognitive impairment in mice
Authors: Frost Paula S. , Barros-Aragão Fernanda , da Silva Rachel T. , Venancio Aline , Matias Isadora , Lyra e Silva Natalia M. , Kincheski Grasielle C. , Pimentel-Coelho Pedro M. , De Felice Fernanda G. , Gomes Flávia C. A. , Ferreira Sergio T. , Figueiredo Claudia P. , Clarke Julia R. 
Published: April 2019

AbstractHarmful environmental stimuli during critical stages of development can profoundly affect behavior and susceptibility to diseases. Alzheimer disease (AD) is the most frequent neurodegenerative disease, and evidence suggest that inflammatory conditions act cumulatively, contributing to disease onset. Here we investigated whether infection early in life can contribute to synapse damage and cognitive impairment induced by amyloid-β oligomers (AβOs), neurotoxins found in AD brains. To this end, wild-type mice were subjected to neonatal (post-natal day 4) infection by Escherichia coli (1 × 104 CFU/g), the main cause of infection in low-birth-weight premature infants in the US. E. coli infection caused a transient inflammatory response in the mouse brain starting shortly after infection. Although infected mice performed normally in behavioral tasks in adulthood, they showed increased susceptibility to synapse damage and memory impairment induced by low doses of AβOs (1 pmol; intracerebroventricular) in the novel object recognition paradigm. Using in vitro and in vivo approaches, we show that microglial cells from E. coli-infected mice undergo exacerbated activation when exposed to low doses of AβOs. In addition, treatment of infected pups with minocycline, an antibiotic that inhibits microglial pro-inflammatory polarization, normalized microglial response to AβOs and restored normal susceptibility of mice to oligomer-induced cognitive impairment. Interestingly, mice infected with by E. coli (1 × 104 CFU/g) during adolescence (post-natal day 21) or adulthood (post-natal day 60) showed normal cognitive performance even in the presence of AβOs (1 pmol), suggesting that only infections at critical stages of development may lead to increased susceptibility to amyloid-β-induced toxicity. Altogether, our findings suggest that neonatal infections can modulate microglial response to AβOs into adulthood, thus contributing to amyloid-β-induced synapse damage and cognitive impairment.
Multi-region sequencing unveils novel actionable targets and spatial heterogeneity in esophageal squamous cell carcinoma
Authors: Yan Ting , Cui Heyang , Zhou Yong , Yang Bin , Kong Pengzhou , Zhang Yingchun , Liu Yiqian , Wang Bin , Cheng Yikun , Li Jiayi , Guo Shixing , Xu Enwei , Liu Huijuan , Cheng Caixia , Zhang Ling , Chen Ling , Zhuang Xiaofei , Qian Yu , Yang Jian , Ma Yanchun , Li Hongyi , Wang Fang , Liu Jing , Liu Xuefeng , Su Dan , Wang Yan , Sun Ruifang , Guo Shiping , Li Yaoping , Cheng Xiaolong , Liu Zhihua , Zhan Qimin , Cui Yongping 
Published: April 2019

AbstractEsophageal squamous cell carcinoma (ESCC) ranks fourth among cancer-related deaths in China due to the lack of actionable molecules. We performed whole-exome and T-cell receptor (TCR) repertoire sequencing on multi-regional tumors, normal tissues and blood samples from 39 ESCC patients. The data revealed 12.8% of ERBB4 mutations at patient level and functional study supported its oncogenic role. 18% of patients with early BRCA1/2 variants were associated with high-level contribution of signature 3, which was validated in an independent large cohort (n = 508). Furthermore, knockdown of BRCA1/2 dramatically increased sensitivity to cisplatin in ESCC cells. 5% of patients harbored focal high-level amplification of CD274 that led to massive expression of PD-L1, and might be more sensitive to immune checkpoint blockade. Finally, we found a tight correlation between genomic and TCR repertoire intra-tumor heterogeneity (ITH). Collectively, we reveal high-level ITH in ESCC, identify several potential actionable targets and may provide novel insight into ESCC treatment.
The carbon footprint of the U.S. multinationals’ foreign affiliates
Authors: López Luis-Antonio , Cadarso María-Ángeles , Zafrilla Jorge , Arce Guadalupe 
Published: April 2019

AbstractMultinational enterprises (MNE) need to be a part of the solution in the fight against climate change, as claimed by investors and consumers, reducing emissions within their operations and supply chains. This paper measures the carbon footprint of U.S. MNE foreign affiliates (US-MNE) operating beyond the U.S. borders. Using a multiregional input-output model and information about US-MNE activities, the US-MNE carbon footprint ranks US-MNE as the 12th top emitter of the world. In relative terms, one dollar of value added generated by US-MNE affiliates operating abroad requires higher emissions than the domestic average and the ratio increases when only developing host countries are considered. Only 8% of total carbon footprint returns to the U.S. as virtual carbon embodied in the U.S. final consumption. Potential technology transfers between the U.S. parent company and affiliates to reduce US-MNE carbon footprint have been performed to evaluate potential rippled effects of mitigation actions.
Plasmon-enhanced light–matter interactions and applications
Authors: Yu Huakang , Peng Yusi , Yang Yong , Li Zhi-Yuan 
Published: April 2019

AbstractSurface plasmons are coherent and collective electron oscillations confined at the dielectric–metal interface. Benefitting from the inherent subwavelength nature of spatial profile, surface plasmons can greatly accumulate the optical field and energy on the nanoscale and dramatically enhance various light–matter interactions. The properties of surface plasmons are strongly related to materials and structures, so that metals, semiconductors and two-dimensional materials with various morphologies and structures can have alternating plasmonic wavelengths ranging from ultraviolet, visible, near infrared to far infrared. Because the electric field can be enhanced by orders of magnitude within plasmonic structures, various light–matter interaction processes including fluorescence, Raman scattering, heat generation, photoacoustic effects, photocatalysis, nonlinear optical conversion, and solar energy conversion, can be significantly enhanced and these have been confirmed by both theoretical, computational and experimental studies. In this review, we present a concise introduction and discussion of various plasmon-enhanced light–matter interaction processes. We discuss the physical and chemical principles, influencing factors, computational and theoretical methods, and practical applications of these plasmon-enhanced processes and phenomena, with a hope to deliver guidelines for constructing future high-performance plasmonic devices and technologies.
Parsimonious Gene Correlation Network Analysis (PGCNA): a tool to define modular gene co-expression for refined molecular stratification in cancer
Authors: Care Matthew A. , Westhead David R. , Tooze Reuben M. 
Published: April 2019

AbstractCancers converge onto shared patterns that arise from constraints placed by the biology of the originating cell lineage and microenvironment on programs driven by oncogenic events. Here we define consistent expression modules reflecting this structure in colon and breast cancer by exploiting expression data resources and a new computationally efficient approach that we validate against other comparable methods. This approach, Parsimonious Gene Correlation Network Analysis (PGCNA), allows comparison of network structures between these cancer types identifying shared modules of gene co-expression reflecting: cancer hallmarks, functional and structural gene batteries, copy number variation and biology of originating lineage. These networks along with the mapping of outcome data at gene and module level provide an interactive resource that generates context for relationships between genes within and between such modules. Assigning module expression values (MEVs) provides a tool to summarize network level gene expression in individual cases illustrating potential utility in classification and allowing analysis of linkage between module expression and mutational state. Exploiting TCGA data thus defines both recurrent patterns of association between module expression and mutation at data-set level, and exemplifies the polarization of mutation patterns with the leading edge of module expression at individual case level. We illustrate the scalable nature of the approach within immune response related modules, which in the context of breast cancer demonstrates the selective association of immune subsets, in particular mast cells, with the underlying mutational pattern. Together our analyses provide evidence for a generalizable framework to enhance molecular stratification in cancer.
Physical activity, sleep and cardiovascular health data for 50,000 individuals from the MyHeart Counts Study
Authors: Hershman Steven G. , Bot Brian M. , Shcherbina Anna , Doerr Megan , Moayedi Yasbanoo , Pavlovic Aleksandra , Waggott Daryl , Cho Mildred K. , Rosenberger Mary E. , Haskell William L. , Myers Jonathan , Champagne Mary Ann , Mignot Emmanuel , Salvi Dario , Landray Martin , Tarassenko Lionel , Harrington Robert A. , Yeung Alan C. , McConnell Michael V. , Ashley Euan A. 
Published: April 2019

AbstractStudies have established the importance of physical activity and fitness for long-term cardiovascular health, yet limited data exist on the association between objective, real-world large-scale physical activity patterns, fitness, sleep, and cardiovascular health primarily due to difficulties in collecting such datasets. We present data from the MyHeart Counts Cardiovascular Health Study, wherein participants contributed data via an iPhone application built using Apple’s ResearchKit framework and consented to make this data available freely for further research applications. In this smartphone-based study of cardiovascular health, participants recorded daily physical activity, completed health questionnaires, and performed a 6-minute walk fitness test. Data from English-speaking participants aged 18 years or older with a US-registered iPhone who agreed to share their data broadly and who enrolled between the study’s launch and the time of the data freeze for this data release (March 10 2015–October 28 2015) are now available for further research. It is anticipated that releasing this large-scale collection of real-world physical activity, fitness, sleep, and cardiovascular health data will enable the research community to work collaboratively towards improving our understanding of the relationship between cardiovascular indicators, lifestyle, and overall health, as well as inform mobile health research best practices.
Structural analyses of NudT16–ADP-ribose complexes direct rational design of mutants with improved processing of poly(ADP-ribosyl)ated proteins
Authors: Thirawatananond Puchong , McPherson Robert Lyle , Malhi Jasmine , Nathan Sara , Lambrecht Michael J. , Brichacek Matthew , Hergenrother Paul J. , Leung Anthony K. L. , Gabelli Sandra B. 
Published: April 2019

AbstractADP-ribosylation is a post-translational modification that occurs on chemically diverse amino acids, including aspartate, glutamate, lysine, arginine, serine and cysteine on proteins and is mediated by ADP-ribosyltransferases, including a subset commonly known as poly(ADP-ribose) polymerases. ADP-ribose can be conjugated to proteins singly as a monomer or in polymeric chains as poly(ADP-ribose). While ADP-ribosylation can be reversed by ADP-ribosylhydrolases, this protein modification can also be processed to phosphoribosylation by enzymes possessing phosphodiesterase activity, such as snake venom phosphodiesterase, mammalian ectonucleotide pyrophosphatase/phosphodiesterase 1, Escherichia coli RppH, Legionella pneumophila Sde and Homo sapiens NudT16 (HsNudT16). Our studies here sought to utilize X-ray crystallographic structures of HsNudT16 in complex with monomeric and dimeric ADP-ribose in identifying the active site for binding and processing free and protein-conjugated ADP-ribose into phosphoribose forms. These structural data guide rational design of mutants that widen the active site to better accommodate protein-conjugated ADP-ribose. We identified that several HsNudT16 mutants (Δ17, F36A, and F61S) have reduced activity for free ADP-ribose, similar processing ability against protein-conjugated mono(ADP-ribose), but improved catalytic efficiency for protein-conjugated poly(ADP-ribose). These HsNudT16 variants may, therefore, provide a novel tool to investigate different forms of ADP-ribose.
Behavior of mice aboard the International Space Station
Authors: Ronca April E. , Moyer Eric L. , Talyansky Yuli , Lowe Moniece , Padmanabhan Shreejit , Choi Sungshin , Gong Cynthia , Cadena Samuel M. , Stodieck Louis , Globus Ruth K. 
Published: April 2019

AbstractInterest in space habitation has grown dramatically with planning underway for the first human transit to Mars. Despite a robust history of domestic and international spaceflight research, understanding behavioral adaptation to the space environment for extended durations is scant. Here we report the first detailed behavioral analysis of mice flown in the NASA Rodent Habitat on the International Space Station (ISS). Following 4-day transit from Earth to ISS, video images were acquired on orbit from 16- and 32-week-old female mice. Spaceflown mice engaged in a full range of species-typical behaviors. Physical activity was greater in younger flight mice as compared to identically-housed ground controls, and followed the circadian cycle. Within 9–11 days after launch, younger (but not older), mice began to exhibit distinctive circling or ‘race-tracking’ behavior that evolved into a coordinated group activity. Organized group circling behavior unique to spaceflight may represent stereotyped motor behavior, rewarding effects of physical exercise, or vestibular sensation produced via self-motion. Affording mice the opportunity to grab and run in the RH resembles physical activities that the crew participate in routinely. Our approach yields a useful analog for better understanding human responses to spaceflight, providing the opportunity to assess how physical movement influences responses to microgravity.
Accurate target identification for Mycobacterium tuberculosis endoribonuclease toxins requires expression in their native host
Authors: Cintrón Melvilí , Zeng Ju-Mei , Barth Valdir C. , Cruz Jonathan W. , Husson Robert N. , Woychik Nancy A. 
Published: April 2019

AbstractThe Mycobacterium tuberculosis genome harbors an unusually high number of toxin-antitoxin (TA) systems. These TA systems have been implicated in establishing the nonreplicating persistent state of this pathogen during latent tuberculosis infection. More than half of the M. tuberculosis TA systems belong to the VapBC (virulence associated protein) family. In this work, we first identified the RNA targets for the M. tuberculosis VapC-mt11 (VapC11, Rv1561) toxin in vitro to learn more about the general function of this family of toxins. Recombinant VapC-mt11 cleaved 15 of the 45 M. tuberculosis tRNAs at a single site within their anticodon stem loop (ASL) to generate tRNA halves. Cleavage was dependent on the presence of a GG consensus sequence immediately before the cut site and a structurally intact ASL. However, in striking contrast to the broad enzyme activity exhibited in vitro, we used a specialized RNA-seq method to demonstrate that tRNA cleavage was highly specific in vivo. Expression of VapC-mt11 in M. tuberculosis resulted in cleavage of only two tRNA isoacceptors containing the GG consensus sequence, tRNAGln32-CUG and tRNALeu3-CAG. Therefore, our results indicate that although in vitro studies are useful for identification of the class of RNA cleaved and consensus sequences required for accurate substrate recognition by endoribonuclease toxins, definitive RNA target identification requires toxin expression in their native host. The restricted in vivo specificity of VapC-mt11 suggests that it may be enlisted to surgically manipulate pathogen physiology in response to stress.
Exome array analysis of rare and low frequency variants in amyotrophic lateral sclerosis
Authors: Dekker Annelot M. , Diekstra Frank P. , Pulit Sara L. , Tazelaar Gijs H. P. , van der Spek Rick A. , van Rheenen Wouter , van Eijk Kristel R. , Calvo Andrea , Brunetti Maura , Damme Philip Van , Robberecht Wim , Hardiman Orla , McLaughlin Russell , Chiò Adriano , Sendtner Michael , Ludolph Albert C. , Weishaupt Jochen H. , Pardina Jesus S. Mora , van den Berg Leonard H. , Veldink Jan H. 
Published: April 2019

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects 1 in ~350 individuals. Genetic association studies have established ALS as a multifactorial disease with heritability estimated at ~61%, and recent studies show a prominent role for rare variation in its genetic architecture. To identify rare variants associated with disease onset we performed exome array genotyping in 4,244 cases and 3,106 controls from European cohorts. In this largest exome-wide study of rare variants in ALS to date, we performed single-variant association testing, gene-based burden, and exome-wide individual set-unique burden (ISUB) testing to identify single or aggregated rare variation that modifies disease risk. In single-variant testing no variants reached exome-wide significance, likely due to limited statistical power. Gene-based burden testing of rare non-synonymous and loss-of-function variants showed NEK1 as the top associated gene. ISUB analysis did not show an increased exome-wide burden of deleterious variants in patients, possibly suggesting a more region-specific role for rare variation. Complete summary statistics are released publicly. This study did not implicate new risk loci, emphasizing the immediate need for future large-scale collaborations in ALS that will expand available sample sizes, increase genome coverage, and improve our ability to detect rare variants associated to ALS.
Rare variants in SLC5A10 are associated with serum 1,5-anhydroglucitol (1,5-AG) in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Loomis Stephanie J. , Köttgen Anna , Li Man , Tin Adrienne , Coresh Josef , Boerwinkle Eric , Gibbs Richard , Muzny Donna , Pankow James , Selvin Elizabeth , Duggal Priya 
Published: April 2019

AbstractSerum 1,5-anhydroglucitol (1,5-AG) is an emerging biomarker used to monitor glycemic control in persons with diabetes. We performed whole-exome sequencing, examining the association between rare, coding genetic variants and 1,5-AG among European ancestry (N = 6,589) and African ancestry (N = 2,309) participants without diagnosed diabetes in the Atherosclerosis Risk in Communities (ARIC) Study. Five variants representing 3 independent signals on chromosome 17 in SLC5A10, a glucose transporter not previously known to transport 1,5-AG, were associated with 1,5-AG levels up to 10.38 µg/mL lower per allele (1,5-AG range 3.4–32.8 µg/mL) in the European ancestry sample and validated in the African ancestry sample. Together these variants explained 6% of the variance in 1,5-AG. Two of these variants (rs61741107, p = 8.85E-56; rs148178887, p = 1.13E-36) were rare, nonsynonymous, and predicted to be damaging or deleterious by multiple algorithms. Gene-based SKAT-O analysis supported these results (SLC5A10 p = 5.13E-64 in European ancestry, validated in African ancestry, p = 0.006). Interestingly, these novel variants are not associated with other biomarkers of hyperglycemia or diabetes (p > 0.2). The large effect sizes and protein-altering, multiple independent signals suggest SLC5A10 may code for an important transporter of 1,5-AG in the kidney, with a potential nonglucose-related effect on 1,5-AG, impacting its clinical utility as a diabetes biomarker in this subpopulation.
Small-Molecule Ferroptotic Agents with Potential to Selectively Target Cancer Stem Cells
Authors: Taylor William R. , Fedorka Sara R. , Gad Ibtissam , Shah Ronit , Alqahtani Hanan D. , Koranne Radhika , Kuganesan Nishanth , Dlamini Samkeliso , Rogers Tim , Al-Hamashi Ayad , Kholodovych Veronika , Barudi Yusuf , Junk Damian , Rashid Maisha S. , Jackson Mark W. , Tillekeratne L. M. Viranga 
Published: April 2019

AbstractEffective management of advanced cancer requires systemic treatment including small molecules that target unique features of aggressive tumor cells. At the same time, tumors are heterogeneous and current evidence suggests that a subpopulation of tumor cells, called tumor initiating or cancer stem cells, are responsible for metastatic dissemination, tumor relapse and possibly drug resistance. Classical apoptotic drugs are less effective against this critical subpopulation. In the course of generating a library of open-chain epothilones, we discovered a new class of small molecule anticancer agents that has no effect on tubulin but instead kills selected cancer cell lines by harnessing reactive oxygen species to induce ferroptosis. Interestingly, we find that drug sensitivity is highest in tumor cells with a mesenchymal phenotype. Furthermore, these compounds showed enhanced toxicity towards mesenchymal breast cancer populations with cancer stem cell properties in vitro. In summary, we have identified a new class of small molecule ferroptotic agents that warrant further investigation.
Effect of the Nano Crystal Size on the X-ray Diffraction Patterns of Biogenic Hydroxyapatite from Human, Bovine, and Porcine Bones
Authors: Londoño-Restrepo Sandra M. , Jeronimo-Cruz Rodrigo , Millán-Malo Beatriz M. , Rivera-Muñoz Eric M. , Rodriguez-García Mario E. 
Published: April 2019

AbstractThis paper focuses on the study of the effect of the change of the crystal size on the shape and width of the X-ray diffraction patterns for defatted and deproteinized bones as well as incinerated biogenic hydroxyapatite obtained from bovine, porcine, and human bones. Inductively Couple Plasma showed the presence of some ions such as Mg, K, Al, Fe, Zn, and Na for all samples. The nanometric size of the crystals was determined through High Resolution Transmission Electron Microscopy in which ordered crystals were found. The calcination of raw clean bones at 720 °C produced a transition of crystal size from nano to micro due to a coalescence phenomenon, this was accompanied by a decrease of the peak width of the X-ray diffraction patterns due to the decrease of the inelastic scattering contribution from the microcrystals. A simulation of the effect of the crystallite size on the shape and width of the X-ray patterns was done using PDF-4 software which confirmed that raw ordered bone crystals produce broad peaks which so far have been erroneously assigned to polycrystalline hydroxyapatite with low crystalline quality.