bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stratigraphic Control of Frontal Décollement Level and Structural Vergence and Implications for Tsunamigenic Earthquake Hazard in Sumatra, Indonesia
Authors: Bradley Kyle , Qin Yanfang , Carton Hélène , Hananto Nugroho , Villanueva‐Robles Fernando , Leclerc Fréderique , Shengji Wei , Tapponier Paul , Sieh Kerry , Singh Satish 
Published: March 2019

AbstractPropagation of fault rupture to the seafloor is a likely cause of enhanced tsunami generation during megathrust earthquakes. New, high‐resolution seismic reflection profiles and swath bathymetry collected across the northern limit of the Mw 7.8, 25 October 2010 Mentawai tsunami earthquake rupture reveal significant and systematic lateral variations in both the stratigraphic level of the frontal Sunda megathrust and the vergence of its frontal ramp faults. Where ramp faults are uniformly seaward vergent, the décollement resides on top of a strong reflector marking the inferred top of pelagic sediments. Where ramp faults are bivergent (both landward and seaward), the décollement is localized within the subducting clastic sequence, above a xseismically transparent unit inferred to be distal fan muds. Where ramp faults are uniformly landward vergent, the décollement is directly on top of the oceanic crust of the subducting Investigator Fracture Zone. Enhanced surface uplift and tsunamigenesis during the 2010 tsunamigenic earthquake appear to have coincided with propagation of rupture into frontal areas with well‐developed structural bivergence. Frontal bivergence is a geological signal of low basal traction during accrual of slip, and offshore of Sumatra this structural style may mark areas of enhanced tsunami hazard posed by small‐magnitude, shallow megathrust ruptures that propagate into the incoming terrigenous sequence at near‐trench levels.
β-Thujaplicin induces autophagic cell death, apoptosis, and cell cycle arrest through ROS-mediated Akt and p38/ERK MAPK signaling in human hepatocellular carcinoma
Authors: Zhang Guangya , He Jiangping , Ye Xiaofei , Zhu Jing , Hu Xi , Shen Minyan , Ma Yuru , Mao Ziming , Song Huaidong , Chen Fengling 
Published: March 2019

AbstractHepatocellular carcinoma (HCC), a common liver malignancy worldwide, has high morbidity and mortality. β-Thujaplicin, a tropolone derivative, has been used in some health-care products and clinical adjuvant drugs, but its use for HCC is unknown. In this study, we found that β-Thujaplicin inhibits the growth of HCC cells, but not normal liver cells, with nanomolar potency. Mechanistically, we found that β-Thujaplicin could induce autophagy, as judged by western blot, confocal microscopy, and transmission electron microscopy. Further using β-Thujaplicin combined with an autophagy blocker or agonist treatment HepG2 cells, we found that β-Thujaplicin induced autophagic cell death (ACD) mediated by ROS caused inhibition of the Akt-mTOR signaling pathway. Moreover, β-Thujaplicin triggered HepG2 apoptosis and increased cleaved PARP1, cleaved caspase-3, and Bax/Bcl-2 ratio, which indicated that β-Thujaplicin induced apoptosis mediated by the mitochondrial-dependent pathway. We also found that increased expression of p21 and decreased expression of CDK7, Cyclin D1, and Cyclin A2 participating in β-Thujaplicin caused the S-phase arrest. It seems that β-Thujaplicin exerts these functions by ROS-mediated p38/ERK MAPK but not by JNK signaling pathway activation. Consistent with in vitro findings, our in vivo study verified that β-Thujaplicin treatment significantly reduced HepG2 tumor xenograft growth. Taken together these findings suggest that β-Thujaplicin have an ability of anti-HCC cells and may conducively promote the development of novel anti-cancer agents.
Absence of the proteoglycan decorin reduces glucose tolerance in overfed male mice
Authors: Svärd Jessica , Røst Therese H. , Sommervoll Camilla E. N. , Haugen Christine , Gudbrandsen Oddrun A. , Mellgren Anne E. , Rødahl Eyvind , Fernø Johan , Dankel Simon N. , Sagen Jørn V. , Mellgren Gunnar 
Published: March 2019

AbstractStudies have implicated the extracellular matrix (ECM) of adipose tissue in insulin resistance. The proteoglycan decorin, a component of ECM, has been associated with glucose tolerance, but possible causal effects on metabolism remain to be explored. We here sought to determine metabolic consequences of loss of decorin in mice (DcnKO). DcnKO mice were fed a low-fat (LF) or high-fat (HF) diet for 10 weeks and body weight and food intake was recorded. An intraperitoneal glucose tolerance test was performed after eight weeks. Blood samples and adipose, liver and muscle tissues were collected at sacrifice. Global gene expression was measured in adipose tissue, and expression of decorin was also analyzed in human adipose samples. DcnKO mice showed increased feed efficiency during overfeeding and impaired glucose tolerance. Adipose leptin mRNA and circulating leptin levels were elevated in DcnKO mice, along with a downregulation of genes involved in ECM organization and triglyceride biosynthesis, and an upregulation of adipose genes involved in complement and coagulation cascades. Consistent with a protective metabolic role for decorin, in obese patients we found increased adipose decorin expression after profound fat loss, particularly in the stromal vascular fraction. Loss of decorin in mice caused impaired glucose tolerance in association with increased feed efficiency and altered gene expression in adipose tissue. Our data provide evidence that decorin is an important factor for maintaining glucose tolerance.
A transient window of hypothyroidism alters neural progenitor cells and results in abnormal brain development
Authors: O’Shaughnessy Katherine L. , Thomas Susan E. , Spring Stephanie R. , Ford Jermaine L. , Ford Richard L. , Gilbert Mary E. 
Published: March 2019

AbstractCortical heterotopias are clusters of ectopic neurons in the brain and are associated with neurodevelopmental disorders like epilepsy and learning disabilities. We have previously characterized the robust penetrance of a heterotopia in a rat model, induced by thyroid hormone (TH) disruption during gestation. However, the specific mechanism by which maternal TH insufficiency results in this birth defect remains unknown. Here we first determined the developmental window susceptible to endocrine disruption and describe a cellular mechanism responsible for heterotopia formation. We show that five days of maternal goitrogen treatment (10 ppm propylthiouracil) during the perinatal period (GD19-PN2) induces a periventricular heterotopia in 100% of the offspring. Beginning in the early postnatal brain, neurons begin to aggregate near the ventricles of treated animals. In parallel, transcriptional and architectural changes of this region were observed including decreased Sonic hedgehog (Shh) expression, abnormal cell adhesion, and altered radial glia morphology. As the ventricular epithelium is juxtaposed to two sources of brain THs, the cerebrospinal fluid and vasculature, this progenitor niche may be especially susceptible to TH disruption. This work highlights the spatiotemporal vulnerabilities of the developing brain and demonstrates that a transient period of TH perturbation is sufficient to induce a congenital abnormality.
Microscale Temperature Shaping Using Spatial Light Modulation on Gold Nanoparticles
Authors: Durdevic Ljiljana , Robert Hadrien M. L. , Wattellier Benoit , Monneret Serge , Baffou Guillaume 
Published: March 2019

AbstractHeating on the microscale using focused lasers gave rise to recent applications, e.g., in biomedicine, biology and microfluidics, especially using gold nanoparticles as efficient nanoabsorbers of light. However, such an approach naturally leads to nonuniform, Gaussian-like temperature distributions due to the diffusive nature of heat. Here, we report on an experimental means to generate arbitrary distributions of temperature profiles on the micrometric scale (e.g. uniform, linear, parabolic, etc) consisting in illuminating a uniform gold nanoparticle distribution on a planar substrate using spatially contrasted laser beams, shaped using a spatial light modulator (SLM). We explain how to compute the light pattern and the SLM interferogram to achieve the desired temperature distribution, and demonstrate the approach by carrying out temperature measurements using quantitative wavefront sensing.
Utilization of the high spatial-frequency component in adaptive beam shaping by using a virtual diagonal phase grating
Authors: Nakata Yoshiki , Osawa Kazuhito , Miyanaga Noriaki 
Published: March 2019

AbstractA square flattop beam is a fundamental shape that is in high demand in various applications, such as ultra-high-power lasers, uniform surface processing and medical engineering. In this experiment, a new and simple scheme of the adaptive beam shaping system to generate a square flattop shape with high uniformity and edge steepness using virtual diagonal phase grating encoded on a spatial-light modulator and a 4f system is proposed. The grating vector kg is non-parallel to the normal vectors kx and ky of the objective beam profile to be extracted; thus, the residual and extracted components hit separately on the Fourier plane of the 4f system. Consequently, using a spatial-frequency filter passing components parallel to kx and ky, the residual components are blocked by the filter without loss of the high spatial-frequency domain of the extracted component. When the width of the filter was 1.0 mm, the edge of the shaped beam increased in height within 20 μm, which is less than 20% of that obtained with conventional vertical phase grating.
The Impact of Shift Work on Sleep, Alertness and Performance in Healthcare Workers
Authors: Ganesan Saranea , Magee Michelle , Stone Julia E. , Mulhall Megan D. , Collins Allison , Howard Mark E. , Lockley Steven W. , Rajaratnam Shantha M. W. , Sletten Tracey L. 
Published: March 2019

AbstractShift work is associated with impaired alertness and performance due to sleep loss and circadian misalignment. This study examined sleep between shift types (day, evening, night), and alertness and performance during day and night shifts in 52 intensive care workers. Sleep and wake duration between shifts were evaluated using wrist actigraphs and diaries. Subjective sleepiness (Karolinska Sleepiness Scale, KSS) and Psychomotor Vigilance Test (PVT) performance were examined during day shift, and on the first and subsequent night shifts (3rd, 4th or 5th). Circadian phase was assessed using urinary 6-sulphatoxymelatonin rhythms. Sleep was most restricted between consecutive night shifts (5.74 ± 1.30 h), consecutive day shifts (5.83 ± 0.92 h) and between evening and day shifts (5.20 ± 0.90 h). KSS and PVT mean reaction times were higher at the end of the first and subsequent night shift compared to day shift, with KSS highest at the end of the first night. On nights, working during the circadian acrophase of the urinary melatonin rhythm led to poorer outcomes on the KSS and PVT. In rotating shift workers, early day shifts can be associated with similar sleep restriction to night shifts, particularly when scheduled immediately following an evening shift. Alertness and performance remain most impaired during night shifts given the lack of circadian adaptation to night work. Although healthcare workers perceive themselves to be less alert on the first night shift compared to subsequent night shifts, objective performance is equally impaired on subsequent nights.
CXCL4/PF4 is a predictive biomarker of cardiac differentiation potential of human induced pluripotent stem cells
Authors: Ohashi Fumiya , Miyagawa Shigeru , Yasuda Satoshi , Miura Takumi , Kuroda Takuya , Itoh Masayoshi , Kawaji Hideya , Ito Emiko , Yoshida Shohei , Saito Atsuhiro , Sameshima Tadashi , Kawai Jun , Sawa Yoshiki , Sato Yoji 
Published: March 2019

AbstractSelection of human induced pluripotent stem cell (hiPSC) lines with high cardiac differentiation potential is important for regenerative therapy and drug screening. We aimed to identify biomarkers for predicting cardiac differentiation potential of hiPSC lines by comparing the gene expression profiles of six undifferentiated hiPSC lines with different cardiac differentiation capabilities. We used three platforms of gene expression analysis, namely, cap analysis of gene expression (CAGE), mRNA array, and microRNA array to efficiently screen biomarkers related to cardiac differentiation of hiPSCs. Statistical analysis revealed candidate biomarker genes with significant correlation between the gene expression levels in the undifferentiated hiPSCs and their cardiac differentiation potential. Of the candidate genes, PF4 was validated as a biomarker expressed in undifferentiated hiPSCs with high potential for cardiac differentiation in 13 additional hiPSC lines. Our observations suggest that PF4 may be a useful biomarker for selecting hiPSC lines appropriate for the generation of cardiomyocytes.
Memantine prodrug as a new agent for Alzheimer’s Disease
Authors: Sestito Simona , Daniele Simona , Pietrobono Deborah , Citi Valentina , Bellusci Lorenza , Chiellini Grazia , Calderone Vincenzo , Martini Claudia , Rapposelli Simona 
Published: March 2019

AbstractHydrogen sulphide has recently drawn much attention due to its potent anti-inflammatory and neuroprotective roles in brain functions. The purpose of the current study was to exploit these beneficial properties of H2S to design a new agent for the treatment of Alzheimer’s disease (AD). To pursue our aims, we replaced the free amine group of memantine with an isothiocyanate functionality as a putative H2S-donor moiety. The new chemical entity, named memit, was then tested in vitro to determine whether it retains the pharmacological profile of the “native drug”, while also providing a source of H2S in the CNS. Indeed, Memit showed the ability to release H2S through a cysteine-mediated mechanism, thus generating memantine. Moreover, the new hybrid molecule exerts protective effects against neuronal inflammation and induces a drastic fall in ROS production. In addition, memit was also able to reduce the Aβ(1-42) self-induced aggregation and exerted cytoprotective effect against Aβ oligomers-induced damage in both human neurons and rat microglia cells. Finally, similarly to memantine, the new compound promotes autophagy, a complex process required for cellular homeostasis in cell survival that results to be altered in neurodegenerative diseases. In conclusion, our study revealed that memit is a prodrug of memantine. Further in vivo studies will be necessary to fully investigate the synergic or cumulative effects due to the H2S-releasing moiety and the native drug.
Pistacia vera L. oleoresin and levofloxacin is a synergistic combination against resistant Helicobacter pylori strains
Authors: Di Lodovico Silvia , Napoli Edoardo , Di Campli Emanuela , Di Fermo Paola , Gentile Davide , Ruberto Giuseppe , Nostro Antonia , Marini Emanuela , Cellini Luigina , Di Giulio Mara 
Published: March 2019

AbstractThe increasing multidrug resistance in Helicobacter pylori, also correlated to its biofilm‐forming ability, underlines the need to search novel strategies to improve the eradication rate. Natural compounds are proposed as antibiotic-resistant-breakers capable to restore the efficacy of conventional drugs. Aim of this work was to evaluate the capability of Pistacia vera L. oleoresin (ORS) to synergize with levofloxacin (LVX) against resistant H. pylori strains. The antimicrobial activity of P. vera L. ORS and LVX and their combinations was determined by MIC/MBC (in neutral and acidic environments) and checkerboard tests. The anti-biofilm effect was determined by biomass quantification. In vivo Galleria mellonella model was used to confirm in vitro data. Pistacia vera L. ORS and LVX MICs ranged respectively from 780 to 3120 mg/l and from 0.12 to 2.00 mg/l, at pH 7.0 and 5.5. MBCs were similar to MICs. Pistacia vera L. ORS was able to synergize with LVX, restoring its effectiveness in LVX resistant strains. Pistacia vera L. ORS, LVX and their synergistic combinations displayed significant biofilm reduction. Pistacia vera L. ORS and LVX, showed protective effect against H. pylori infection on G. mellonella (62% and 63% of survival, respectively). Pistacia vera L. ORS can be considered a promising potentiator to restore the effectiveness of LVX tackling the H. pylori antibiotic resistance phenomenon.
Scaling in vitro activity of CYP3A7 suggests human fetal livers do not clear retinoic acid entering from maternal circulation
Authors: Topletz Ariel R. , Zhong Guo , Isoherranen Nina 
Published: March 2019

AbstractAll-trans-retinoic acid (atRA), the active metabolite of vitamin A, is a critical signaling molecule during embryonic and fetal development and is necessary for maternal health. Fetal exposure to endogenous atRA is tightly regulated during gestation in a tissue specific manner and maternal exposure to exogenous retinoids during pregnancy is teratogenic. The clearance of atRA is primarily mediated by the cytochrome P450 (CYP) 26 enzymes, which play an essential role in controlling retinoid gradients during organogenesis. We hypothesized that CYP26 enzymes in the human fetal liver also function as a protective barrier to prevent maternal atRA reaching fetal circulation. Using human fetal liver tissue, we found that the mRNA of CYP26A1 and CYP26B1 enzymes is expressed in the human fetal liver. However, based on inhibition studies, metabolite profiles and correlation of atRA metabolism with testosterone hydroxylation, clearance of atRA in the fetal livers was mediated by CYP3A7. Based on in vitro-to-in vivo scaling, atRA clearance in the fetal liver was quantitatively minimal, thus providing an insufficient maternal-fetal barrier for atRA exposure.
PAmiRDB: A web resource for plant miRNAs targeting viruses
Authors: Satish Deepshikha , Mukherjee Sunil Kumar , Gupta Dinesh 
Published: March 2019

AbstractMicroRNAs (miRNAs) have emerged to be essential constituents of host antiviral-defense mechanisms. The miRNA mediated antiviral mechanism was first experimentally established in animals, which proved that host miRNAs regulate viral gene expression by targeting the animal virus mRNAs. There are comparatively fewer reports about such interactions in plants, however, artificial miRNA studies prove that miRNAs play similar antiviral role in plants too. To explore the extent of this phenomenon in plant genomes, and in the absence of any publicly available resource for prediction of plant miRNAs targeting viruses, we were motivated to predict such interactions of plant miRNAs and viral genes. The intriguing results of the predictions are compiled as a database, which we have named as PAmiRDB. The current version of PAmiRDB includes more than 2600 plant miRNAs and their specific interactions with corresponding targets in approximately 500 viral species (predominantly from the major plant-infecting virus families of geminiviruses and potyviruses). PAmiRDB is a database of known plant miRNAs and their predicted targets in virus genomes. The innovative database query-interface enables global and comprehensive investigation of such predicted interactions between host miRNAs and viral genes. The database integrated-tools also helps researchers to design experiments to confirm such interactions. PAmiRDB is available at http://bioinfo.icgeb.res.in/pamirdb
Clarifying photoluminescence decay dynamics of self-assembled quantum dots
Authors: Man Minh Tan , Lee Hong Seok 
Published: March 2019

AbstractWe studied the temperature-dependent photoluminescence (PL) and time-resolved PL spectra of multilayer CdTe/ZnTe quantum dots (QDs) to understand their carrier dynamics. We demonstrated a method of enhancing the confinement of carriers in CdTe QDs by modulating the number of stacked layers, leading to enhanced acoustic phonons up to 67 μeV and reducing the optical phonon coupling to 20 meV with an average phonon energy of 20 meV. The temperature-dependent decay time could be explained using a simple model of the thermal redistribution of carrier states. Thermal escape from hole states during multiphonon scattering occurred only at high temperatures, whereas blue shifts and enhanced PL intensity were expected to enhance the electron–phonon coupling and confinement-induced mixing among discrete state and continuum states with separation energies of 3.5–7.4 meV. Time-resolved PL measurements probed the electric field screening effect as a function of the strain distribution in QDs and was established to be 2.5 ± 0.2 MV/cm.
Copy number alterations in B-cell development genes, drug resistance, and clinical outcome in pediatric B-cell precursor acute lymphoblastic leukemia
Authors: Steeghs Elisabeth M. P. , Boer Judith M. , Hoogkamer Alex Q. , Boeree Aurélie , de Haas Valerie , de Groot-Kruseman Hester A. , Horstmann Martin A. , Escherich Gabriele , Pieters Rob , den Boer Monique L. 
Published: March 2019

AbstractPediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is associated with a high frequency of copy number alterations (CNAs) in IKZF1, EBF1, PAX5, CDKN2A/B, RB1, BTG1, ETV6, and/or the PAR1 region (henceforth: B-cell development genes). We aimed to gain insight in the association between CNAs in these genes, clinical outcome parameters, and cellular drug resistance. 71% of newly diagnosed pediatric BCP-ALL cases harbored one or more CNAs in these B-cell development genes. The distribution and clinical relevance of these CNAs was highly subtype-dependent. In the DCOG-ALL10 cohort, only loss of IKZF1 associated as single marker with unfavorable outcome parameters and cellular drug resistance. Prednisolone resistance was observed in IKZF1-deleted primary high hyperdiploid cells (~1500-fold), while thiopurine resistance was detected in IKZF1-deleted primary BCR-ABL1-like and non-BCR-ABL1-like B-other cells (~2.7-fold). The previously described risk stratification classifiers, i.e. IKZF1plus and integrated cytogenetic and CNA classification, both predicted unfavorable outcome in the DCOG-ALL10 cohort, and associated with ex vivo drug cellular resistance to thiopurines, or L-asparaginase and thiopurines, respectively. This resistance could be attributed to overrepresentation of BCR-ABL1-like cases in these risk groups. Taken together, our data indicate that the prognostic value of CNAs in B-cell development genes is linked to subtype-related drug responses.
Vagrant birds as a dispersal vector in transoceanic range expansion of vascular plants
Authors: Kalwij Jesse M. , Medan Diego , Kellermann Jürgen , Greve Michelle , Chown Steven L. 
Published: March 2019

AbstractBirds are thought to be important vectors underlying the disjunct distribution patterns of some terrestrial biota. Here, we investigate the role of birds in the colonisation by Ochetophila trinervis (Rhamnaceae), a vascular plant from the southern Andes, of sub-Antarctic Marion Island. The location of O. trinervis on the island far from human activities, in combination with a reconstruction of island visitors’ travel history, precludes an anthropogenic introduction. Notably, three bird species occurring in the southern Andes inland have been observed as vagrants on Marion Island, with the barn swallow Hirundo rustica as the most common one. This vagrant displays long-distance migratory behaviour, eats seeds when insects are in short supply, and has started breeding in South America since the 1980s. Since naturalised O. trinervis has never been found outside the southern Andes and its diaspores are incapable of surviving in seawater or dispersing by wind, a natural avian dispersal event from the Andes to Marion Island, a distance of >7500 km, remains the only probable explanation. Although one self-incompatible shrub seems doomed to remain solitary, its mere establishment on a Southern Ocean island demonstrates the potential of vagrancy as a driver of extreme long-distance dispersal of terrestrial biota.