bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microphysical Properties of Tropical Tropopause Layer Cirrus
Authors: Woods Sarah , Lawson R. Paul , Jensen Eric , Bui T. P. , Thornberry Troy , Rollins Andrew , Pfister Leonhard , Avery Melody 
Published: May 2018

AbstractPervasive cirrus clouds in the tropical tropopause layer (TTL) play an important role in determining the composition of stratospheric air through dehydration of tropospheric air entering the stratosphere. This dehydration affects Earth's energy budget and climate, yet uncertainties remain regarding the microphysical processes that govern TTL cirrus. TTL cirrus were sampled with the NASA Global Hawk UAV for over 30 hr in the Western Pacific in 2014 during the Airborne Tropical TRopopause EXperiment. In situ measurements by a Fast Cloud Droplet Probe and Hawkeye probe (combination Fast Cloud Droplet Probe, Two‐Dimensional Stereo optical array probe, and Cloud Particle Imager) provided particle concentrations and sizing between 1‐ and 1,280‐μm diameter and high resolution images for habit identification. We present the variability in ice concentrations, size distributions, and habits as functions of temperature, altitude, and time since convective influence. Observed ice particles were predominantly small and quasi‐spheroidal in shape, with the percentage of quasi‐spheroids increasing with decreasing temperature. In comparison to the large fraction of the population consisting of quasi‐spheroids, faceted habits (columns, plates, rosettes, and budding rosettes) constituted a smaller percentage of the overall population and exhibited the opposite correlation with temperature. The trend of higher percentages of faceted crystals occurring at warmer temperatures may be due to diffusional growth or aggregation as particles descend through cloud, and/or the more rapid diffusional growth rate at warmer temperatures. Sampling was typically well away from deep convection, however, and very few aggregates were observed, so the trend of higher percentages of faceted habits is likely attributable to diffusional growth.
Regional Distance PL Phase in the Crustal Waveguide—An Analog to the Teleseismic W Phase in the Upper‐Mantle Waveguide
Authors: Furumura Takashi , Kennett B. L. N. 
Published: May 2018

AbstractDense strong ground motion observations of the shallow Mw 6.6 2004 Mid‐Niigata earthquake, Japan, show a strong, moderately long‐period disturbance (5–20 s) immediately following P. The associated ground motion is as large or larger as that in the S waves and surface waves. The nature of this PL phase is revealed with the aid of 3‐D finite difference simulations for heterogeneous crust and mantle structures. A strong near‐field contribution at the nearest stations grades into an interference packet of multiple PmP waves beyond 100 km that develops normal dispersion with prograde motion. This partially trapped P wave in the crustal waveguide loses energy by conversion to SV at the surface, and these S waves are then lost to the mantle. However, the amplification of PL is strong in the presence of near‐surface low‐velocity sediments since conversion to S waves is weakened. The behavior of the PL phase in the crustal waveguide at regional distances is a direct analog of the well‐recognized W phase that travels in the upper‐mantle waveguide. The W phase is a very long period disturbance (100–1,000 s) between P and S phases that can travel to teleseismic distances (1,000–10,000 km) as a superposition of multiple reflections from the mantle that has widely been applied for rapid source inversion for large earthquakes. The PL‐W analogy gives the possibility to extend W‐phase type source inversion to much smaller events, exploiting the early arrival of PL to give rapid warning of damaging long‐period ground motion at regional distances carried by S and surface waves.
Characterizing Global Ozonesonde Profile Variability From Surface to the UT/LS With a Clustering Technique and MERRA‐2 Reanalysis
Authors: Stauffer Ryan M. , Thompson Anne M. , Witte Jacquelyn C. 
Published: May 2018

AbstractOur previous studies employing the self‐organizing map (SOM) clustering technique to ozonesonde data have found significant links among meteorological and chemical regimes, and the shape of the ozone (O3) profile from the troposphere to the lower stratosphere. Those studies, which focused on specific northern hemisphere midlatitude geographical regions, demonstrated the advantages of SOM clustering by quantifying O3 profile variability and the O3/meteorological correspondence. We expand SOM to a global set of ozonesonde profiles spanning 1980 to present from 30 sites to summarize the connections among O3 profiles, meteorology, and chemistry, using the Modern‐Era Retrospective Analysis for Research and Applications, version 2 (MERRA‐2) reanalysis and other ancillary data. Four clusters of O3 mixing ratio profiles from the surface to the upper troposphere/lower stratosphere (UT/LS) are generated for each site, which show dominant profile shapes and typical seasonality (or lack thereof) that generally correspond to latitude (i.e., tropical, subtropical, midlatitude, and polar). Examination of MERRA‐2 output reveals a clear relationship among SOM clusters and covarying meteorological fields (geopotential height, potential vorticity, and tropopause height) for polar and midlatitude sites. However, these relationships break down within ±30° latitude. Carbon monoxide satellite data, along with velocity potential, a proxy for convection, calculated from MERRA‐2 wind fields assist characterization of the tropical and subtropical sites, where biomass burning and convective transport linked to the Madden‐Julian oscillation (MJO) dominate O3 variability. In addition to geophysical characterization of O3 profile variability, these results can be used to evaluate chemical transport model output and satellite measurements of O3 profiles.
Mps1 inhibitors synergise with low doses of taxanes in promoting tumour cell death by enhancement of errors in cell division
Authors: Maia Ana Rita R. , Linder Simon , Song Ji-Ying , Vaarting Chantal , Boon Ute , Pritchard Colin E. J. , Velds Arno , Huijbers Ivo J. , van Tellingen Olaf , Jonkers Jos , Medema René H. 
Published: May 2018

Abstract

Background
Chromosomal instability (CIN) is a common trait of cancer characterised by the continuous gain and loss of chromosomes during mitosis. Excessive levels of CIN can suppress tumour growth, providing a possible therapeutic strategy. The Mps1/TTK kinase has been one of the prime targets to explore this concept, and indeed Mps1 inhibitors synergise with the spindle poison docetaxel in inhibiting the growth of tumours in mice.

Methods
To investigate how the combination of docetaxel and a Mps1 inhibitor (Cpd-5) promote tumour cell death, we treated mice transplanted with BRCA1−/−;TP53−/− mammary tumours with docetaxel and/or Cpd-5. The tumours were analysed regarding their histopathology, chromosome segregation errors, copy number variations and cell death to understand the mechanism of action of the drug combination.

Results
The enhanced efficacy of combining an Mps1 inhibitor with clinically relevant doses of docetaxel is associated with an increase in multipolar anaphases, aberrant nuclear morphologies and cell death. Tumours treated with docetaxel and Cpd-5 displayed more genomic deviations, indicating that chromosome stability is affected mostly in the combinatorial treatment.

Conclusions
Our study shows that the synergy between taxanes and Mps1 inhibitors depends on increased errors in cell division, allowing further optimisation of this treatment regimen for cancer therapy.
Reversible glycosidic switch for secure delivery of molecular nanocargos
Authors: Burnouf Pierre-Alain , Leu Yu-Lin , Su Yu-Cheng , Wu Kenneth , Lin Wei-Chi , Roffler Steve R. 
Published: May 2018

AbstractTherapeutic drugs can leak from nanocarriers before reaching their cellular targets. Here we describe the concept of a chemical switch which responds to environmental conditions to alternate between a lipid-soluble state for efficient cargo loading and a water-soluble state for stable retention of cargos inside liposomes. A cue-responsive trigger allows release of the molecular cargo at specific cellular sites. We demonstrate the utility of a specific glycosidic switch for encapsulation of potent anticancer drugs and fluorescent compounds. Stable retention of drugs in liposomes allowed generation of high tumor/blood ratios of parental drug in tumors after enzymatic hydrolysis of the glycosidic switch in the lysosomes of cancer cells. Glycosidic switch liposomes could cure mice bearing human breast cancer tumors without significant weight loss. The chemical switch represents a general method to load and retain cargos inside liposomes, thereby offering new perspectives in engineering safe and effective liposomes for therapy and imaging.
Distinct homeostatic modulations stabilize reduced postsynaptic receptivity in response to presynaptic DLK signaling
Authors: Goel Pragya , Dickman Dion 
Published: May 2018

AbstractSynapses are constructed with the stability to last a lifetime, yet sufficiently flexible to adapt during injury. Although fundamental pathways that mediate intrinsic responses to neuronal injury have been defined, less is known about how synaptic partners adapt. We have investigated responses in the postsynaptic cell to presynaptic activation of the injury-related Dual Leucine Zipper Kinase pathway at the Drosophila neuromuscular junction. We find that the postsynaptic compartment reduces neurotransmitter receptor levels, thus depressing synaptic strength. Interestingly, this diminished state is stabilized through distinct modulations to two postsynaptic homeostatic signaling systems. First, a retrograde response normally triggered by reduced receptor levels is silenced, preventing a compensatory enhancement in presynaptic neurotransmitter release. However, when global presynaptic release is attenuated, a postsynaptic receptor scaling mechanism persists to adaptively stabilize this diminished neurotransmission state. Thus, the homeostatic set point of synaptic strength is recalibrated to a reduced state as synapses acclimate to injury.
The thioredoxin-1 system is essential for fueling DNA synthesis during T-cell metabolic reprogramming and proliferation
Authors: Muri Jonathan , Heer Sebastian , Matsushita Mai , Pohlmeier Lea , Tortola Luigi , Fuhrer Tobias , Conrad Marcus , Zamboni Nicola , Kisielow Jan , Kopf Manfred 
Published: May 2018

AbstractThe thioredoxin-1 (Trx1) system is an important contributor to cellular redox balance and is a sensor of energy and glucose metabolism. Here we show critical c-Myc-dependent activation of the Trx1 system during thymocyte and peripheral T-cell proliferation, but repression during T-cell quiescence. Deletion of thioredoxin reductase-1 (Txnrd1) prevents expansion the CD4−CD8− thymocyte population, whereas Txnrd1 deletion in CD4+CD8+ thymocytes does not affect further maturation and peripheral homeostasis of αβT cells. However, Txnrd1 is critical for expansion of the activated T-cell population during viral and parasite infection. Metabolomics show that TrxR1 is essential for the last step of nucleotide biosynthesis by donating reducing equivalents to ribonucleotide reductase. Impaired availability of 2′-deoxyribonucleotides induces the DNA damage response and cell cycle arrest of Txnrd1-deficient T cells. These results uncover a pivotal function of the Trx1 system in metabolic reprogramming of thymic and peripheral T cells and provide a rationale for targeting Txnrd1 in T-cell leukemia.
Sex Differences in Cognitive Decline in Subjects with High Likelihood of Mild Cognitive Impairment due to Alzheimer’s disease
Authors: Sohn Dongwha , Shpanskaya Katie , Lucas Joseph E. , Petrella Jeffrey R. , Saykin Andrew J. , Tanzi Rudolph E. , Samatova Nagiza F. , Doraiswamy P. Murali 
Published: May 2018

AbstractSex differences in Alzheimer’s disease (AD) biology and progression are not yet fully characterized. The goal of this study is to examine the effect of sex on cognitive progression in subjects with high likelihood of mild cognitive impairment (MCI) due to Alzheimer’s and followed up to 10 years in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cerebrospinal fluid total-tau and amyloid-beta (Aβ42) ratio values were used to sub-classify 559 MCI subjects (216 females, 343 males) as having “high” or “low” likelihood for MCI due to Alzheimer’s. Data were analyzed using mixed-effects models incorporating all follow-ups. The worsening from baseline in Alzheimer’s Disease Assessment Scale-Cognitive score (mean, SD) (9 ± 12) in subjects with high likelihood of MCI due to Alzheimer’s was markedly greater than that in subjects with low likelihood (1 ± 6, p < 0.0001). Among MCI due to AD subjects, the mean worsening in cognitive score was significantly greater in females (11.58 ± 14) than in males (6.87 ± 11, p = 0.006). Our findings highlight the need to further investigate these findings in other populations and develop sex specific timelines for Alzheimer’s disease progression.
Nanovesicles from adipose-derived mesenchymal stem cells inhibit T lymphocyte trafficking and ameliorate chronic experimental autoimmune encephalomyelitis
Authors: Farinazzo Alessia , Angiari Stefano , Turano Ermanna , Bistaffa Edoardo , Dusi Silvia , Ruggieri Serena , Bonafede Roberta , Mariotti Raffaella , Constantin Gabriela , Bonetti Bruno 
Published: May 2018

AbstractCell based-therapies represent promising strategies for the treatment of neurological diseases. We have previously shown that adipose stem cells (ASC) ameliorate chronic experimental autoimmune encephalomyelitis (EAE). Recent evidence indicates that most ASC paracrine effects are mediated by extracellular vesicles, i.e. micro- and nanovesicles (MVs and NVs). We show that preventive intravenous administration of NVs isolated from ASC (ASC-NVs) before disease onset significantly reduces the severity of EAE and decreases spinal cord inflammation and demyelination, whereas therapeutic treatment with ASC-NVs does not ameliorate established EAE. This treatment marginally inhibits antigen-specific T cell activation, while reducing microglial activation and demyelination in the spinal cord. Importantly, ASC-NVs inhibited integrin-dependent adhesion of encephalitogenic T cellsin vitro, with no effect on adhesion molecule expression. In addition, intravital microscopy showed that encephalitogenic T cells treated with ASC NVs display a significantly reduced rolling and firm adhesion in inflamed spinal cord vessels compared to untreated cells. Our results show that ASC-NVs ameliorate EAE pathogenesis mainly by inhibiting T cell extravasation in the inflamed CNS, suggesting that NVs may represent a novel therapeutic approach in neuro-inflammatory diseases, enabling the safe administration of ASC effector factors.
Neuro-inflammatory effects of photodegradative products of bilirubin
Authors: Jašprová J. , Dal Ben M , Hurný D. , Hwang S. , Žížalová K. , Kotek J. , Wong R. J. , Stevenson D. K. , Gazzin S. , Tiribelli C. , Vítek L. 
Published: May 2018

AbstractPhototherapy was introduced in the early 1950’s, and is the primary treatment of severe neonatal jaundice or Crigler-Najjar syndrome. Nevertheless, the potential biological effects of the products generated from the photodegradation of bilirubin during phototherapy remain unknown. This is very relevant in light of recent clinical observations demonstrating that the use of aggressive phototherapy can increase morbidity or even mortality, in extremely low birthweight (ELBW) infants. The aim of our study was to investigate the effects of bilirubin, lumirubin (LR, its major photo-oxidative product), and BOX A and B (its monopyrrolic oxidative products) on the central nervous system (CNS) using in vitro and ex vivo experimental models. The effects of bilirubin photoproducts on cell viability and expression of selected genes were tested in human fibroblasts, three human CNS cell lines (neuroblastoma SH-SY5Y, microglial HMC3, and glioblastoma U-87 cell lines), and organotypic rat hippocampal slices. Neither bilirubin nor its photo-oxidative products affected cell viability in any of our models. In contrast, LR in biologically-relevant concentrations (25 μM) significantly increased gene expression of several pro-inflammatory genes as well as production of TNF-α in organotypic rat hippocampal slices. These findings might underlie the adverse outcomes observed in ELBW infants undergoing aggressive phototherapy.
Clinically relevant mutations in the ABCG2 transporter uncovered by genetic analysis linked to erythrocyte membrane protein expression
Authors: Zámbó Boglárka , Bartos Zsuzsa , Mózner Orsolya , Szabó Edit , Várady György , Poór Gyula , Pálinkás Márton , Andrikovics Hajnalka , Hegedűs Tamás , Homolya László , Sarkadi Balázs 
Published: May 2018

AbstractThe ABCG2 membrane protein is a key xeno- and endobiotic transporter, modulating the absorption and metabolism of pharmacological agents and causing multidrug resistance in cancer. ABCG2 is also involved in uric acid elimination and its impaired function is causative in gout. Analysis of ABCG2 expression in the erythrocyte membranes of healthy volunteers and gout patients showed an enrichment of lower expression levels in the patients. By genetic screening based on protein expression, we found a relatively frequent, novel ABCG2 mutation (ABCG2-M71V), which, according to cellular expression studies, causes reduced protein expression, although with preserved transporter capability. Molecular dynamics simulations indicated a stumbled dynamics of the mutant protein, while ABCG2-M71V expression in vitro could be corrected by therapeutically relevant small molecules. These results suggest that personalized medicine should consider this newly discovered ABCG2 mutation, and genetic analysis linked to protein expression provides a new tool to uncover clinically important mutations in membrane proteins.
The bipartite mitochondrial genome of Ruizia karukerae (Rhigonematomorpha, Nematoda)
Authors: Kim Taeho , Kern Elizabeth , Park Chungoo , Nadler Steven A. , Bae Yeon Jae , Park Joong-Ki 
Published: May 2018

AbstractMitochondrial genes and whole mitochondrial genome sequences are widely used as molecular markers in studying population genetics and resolving both deep and shallow nodes in phylogenetics. In animals the mitochondrial genome is generally composed of a single chromosome, but mystifying exceptions sometimes occur. We determined the complete mitochondrial genome of the millipede-parasitic nematode Ruizia karukerae and found its mitochondrial genome consists of two circular chromosomes, which is highly unusual in bilateral animals. Chromosome I is 7,659 bp and includes six protein-coding genes, two rRNA genes and nine tRNA genes. Chromosome II comprises 7,647 bp, with seven protein-coding genes and 16 tRNA genes. Interestingly, both chromosomes share a 1,010 bp sequence containing duplicate copies of cox2 and three tRNA genes (trnD, trnG and trnH), and the nucleotide sequences between the duplicated homologous gene copies are nearly identical, suggesting a possible recent genesis for this bipartite mitochondrial genome. Given that little is known about the formation, maintenance or evolution of abnormal mitochondrial genome structures, R. karukerae mtDNA may provide an important early glimpse into this process.
Au nanoparticle@hollow mesoporous carbon with FeCo/graphitic shell nanoparticls as a magnetically recyclable yolk–shell nanocatalyst for catalytic reduction of nitroaromatics
Authors: Hong Yonghoon , Choi In Ae , Seo Won Seok 
Published: May 2018

AbstractWe have developed a highly stable and magnetically recyclable yolk–shell nanocatalyst for catalytic reduction of nitroaromatics. This nanocatalyst is composed of a ~13 nm Au nanoparticle encapsulated in a hollow mesoporous carbon (hmC) shell with a diameter of ~120 nm and a thickness of ~15 nm. The hmC shell contains ~6 nm FeCo/graphitic carbon shell (FeCo/GC) nanoparticles. We have synthesized the Au@hmC-FeCo/GC nanocatalyst by thermal decomposition of Fe and Co precursors in silica of a solid core/mesoporous shell structure containing a Au nanoparticle within the core, subsequent ethylene chemical vapor deposition (CVD), and then removal of the silica by treatment with aqueous HF. The Au@hmC-FeCo/GC has superparamagnetism and high saturation magnetization (29.2 emu g−1) at room temperature. It also shows a type IV sorption isotherm, typical for mesoporous carbon (pore diameter = 3.5 nm), thereby ensuring ready accessibility to the Au core by substrates. We have shown that the Au@hmC-FeCo/GC catalyses the reduction of 4-nitrophenol and 4-nitrotoluene more efficiently than Au nanoparticles do, can be separated very quickly from the reaction mixture using an magnet, and can be reused for the same reduction reaction at least five times without loss of the initial level of catalytic activity.
Region of Interest analysis using mass spectrometry imaging of mitochondrial and sarcomeric proteins in acute cardiac infarction tissue
Authors: Yajima Yuka , Hiratsuka Takuya , Kakimoto Yu , Ogawa Shuichiro , Shima Keisuke , Yamazaki Yuzo , Yoshikawa Kenichi , Tamaki Keiji , Tsuruyama Tatsuaki 
Published: May 2018

AbstractMatrix-assisted laser desorption ionization image mass spectrometry (MALDI-IMS) has been developed for the identification of peptides in various tissues. The MALDI-IMS signal distribution patterns and quantification of the signal intensities of the regions of interest (ROI) with healthy regions were compared for identification of the disease specific biomarkers. We performed a new ROI analysis using the conventional t-test and data number independent Cohen’s d-value analysis. Using these techniques, we analysed heart tissues after acute myocardial infarction (AMI). As a result, IMS signals of mitochondrial adenosine triphosphate synthase alpha subunit (ATP5A), myosin-6/7(MYH6/7), aortic actin, and the myosin light chain 3 (MYL3) were identified in the infarcted region. In particular, the signals of MYH7 are significantly greater in the infarcted region using ROI analysis. ROI analysis using MALDI-IMS may be a promising technique for the identification of biomarkers for pathological studies that involve the comparison of diseased and control areas.
Gestational oral low-dose estradiol-17β induces altered DNA methylation of CDKN2D and PSAT1 in embryos and adult offspring
Authors: van der Weijden Vera A. , Flöter Veronika L. , Ulbrich Susanne E. 
Published: May 2018

AbstractEndocrine disrupting chemicals (EDC) interfere with the natural hormone balance and may induce epigenetic changes through exposure during sensitive periods of development. In this study, the effects of short-term estradiol-17β (E2) exposure on various tissues of pregnant sows (F0) and on day 10 blastocysts (F1) were assessed. Intergenerational effects were investigated in the liver of 1-year old female offspring (F1). During gestation, sows were orally exposed to two low doses and a high dose of E2 (0.05, 10, and 1000 µg/kg body weight/day). In F0, perturbed tissue specific mRNA expression of cell cycle regulation and tumour suppressor genes was found at low and high dose exposure, being most pronounced in the endometrium and corpus luteum. The liver showed the most significant DNA hypomethylation in three target genes; CDKN2D, PSAT1, and RASSF1. For CDKN2D and PSAT1, differential methylation in blastocysts was similar as observed in the F0 liver. Whereas blastocysts showed hypomethylation, the liver of 1-year old offspring showed subtle, but significant hypermethylation. We show that the level of effect of estrogenic EDC, with the periconceptual period as a sensitive time window, is at much lower concentration than currently presumed and propose epigenetics as a sensitive novel risk assessment parameter.