bluuebunny/crossref_metadata_2025_split huggingface dataset:
Populations of the coral species Montastraea cavernosa on the Belize Barrier Reef lack vertical connectivity
Authors: Eckert Ryan J. , Studivan Michael S. , Voss Joshua D. 
Published: May 2019

AbstractLarval connectivity among and within coral reefs is important for sustaining coral metapopulations, enhancing ecosystem resilience through species and genetic diversity, and maintaining reef ecosystems’ structure and functions. This study characterized genetic structure and assessed horizontal and vertical connectivity among populations of the ubiquitous gonochoric broadcast spawning coral Montastraea cavernosa in Belize. Using nine polymorphic microsatellite loci, we genotyped M. cavernosa colonies from four depth zones at four study sites within Belizean marine management zones. Study sites were selected within South Water Caye Marine Reserve (3 sites) and Glover’s Reef Marine Reserve (1 site). Strong contemporary genetic differentiation was observed between relatively shallow M. cavernosa populations (10 m, 16 m) and relatively deep (25 m, 35 m) populations, coinciding with a transition from reef crest to reef slope. These results were consistent across both marine reserves. Vertical and horizontal migration models suggest that all populations were historically panmictic, with little unidirectional migration. The relative local isolation of shallow and mesophotic M. cavernosa populations in Belize, coupled with the importance of Belize’s upper mesophotic populations as potential larval sources for other areas in the Tropical Western Atlantic, reinforces the need for management strategies that conserve coral populations across all depth zones.
Assessing matrix quality by Raman spectroscopy helps predict fracture toughness of human cortical bone
Authors: Unal Mustafa , Uppuganti Sasidhar , Timur Selin , Mahadevan-Jansen Anita , Akkus Ozan , Nyman Jeffry S. 
Published: May 2019

AbstractDeveloping clinical tools that assess bone matrix quality could improve the assessment of a person’s fracture risk. To determine whether Raman spectroscopy (RS) has such potential, we acquired Raman spectra from human cortical bone using microscope- and fiber optic probe-based Raman systems and tested whether correlations between RS and fracture toughness properties were statistically significant. Calculated directly from intensities at wavenumbers identified by second derivative analysis, Amide I sub-peak ratio I1670/I1640, not I1670/I1690, was negatively correlated with Kinit (N = 58; R2 = 32.4%) and J-integral (R2 = 47.4%) when assessed by Raman micro-spectroscopy. Area ratios (A1670/A1690) determined from sub-band fitting did not correlate with fracture toughness. There were fewer correlations between RS and fracture toughness when spectra were acquired by probe RS. Nonetheless, the I1670/I1640 sub-peak ratio again negatively correlated with Kinit (N = 56; R2 = 25.6%) and J-integral (R2 = 39.0%). In best-fit general linear models, I1670/I1640, age, and volumetric bone mineral density explained 50.2% (microscope) and 49.4% (probe) of the variance in Kinit. I1670/I1640 and v1PO4/Amide I (microscope) or just I1670/I1640 (probe) were negative predictors of J-integral (adjusted-R2 = 54.9% or 37.9%, respectively). While Raman-derived matrix properties appear useful to the assessment of fracture resistance of bone, the acquisition strategy to resolve the Amide I band needs to be identified.
Combining patch-clamping and fluorescence microscopy for quantitative reconstitution of cellular membrane processes with Giant Suspended Bilayers
Authors: Velasco-Olmo Ariana , Ormaetxea Gisasola Julene , Martinez Galvez Juan Manuel , Vera Lillo Javier , Shnyrova Anna V. 
Published: May 2019

AbstractIn vitro reconstitution and microscopic visualization of membrane processes is an indispensable source of information about a cellular function. Here we describe a conceptionally novel free-standing membrane template that facilitates such quantitative reconstitution of membrane remodelling at different scales. The Giant Suspended Bilayers (GSBs) spontaneously swell from lipid lamella reservoir deposited on microspheres. GSBs attached to the reservoir can be prepared from virtually any lipid composition following a fast procedure. Giant unilamellar vesicles can be further obtained by GSB detachment from the microspheres. The reservoir stabilizes GSB during deformations, mechanical micromanipulations, and fluorescence microscopy observations, while GSB-reservoir boundary enables the exchange of small solutes with GSB interior. These unique properties allow studying macro- and nano-scale membrane deformations, adding membrane-active compounds to both sides of GSB membrane and applying patch-clamp based approaches, thus making GSB a versatile tool for reconstitution and quantification of cellular membrane trafficking events.
Magnitude and reasons for pre-diagnosis attrition among presumptive multi-drug resistant tuberculosis patients in Bago Region, Myanmar: A mixed methods study
Authors: Oo Tun , Kyaw Khine Wut Yee , Soe Kyaw Thu , Saw Saw , Satyanarayana Srinath , Aung Si Thu 
Published: May 2019

AbstractIn Myanmar, Rifampicin resistant tuberculosis (RR-TB, a proxy for Multi-drug resistant TB) case detection is very low. Our study objectives were to assess the proportion of eligible TB patients who had not undergone RR-TB testing (Xpert-MTB/Rif tests) in Bago Region, Myanmar and to understand the reasons and solutions for non-testing. We conducted a mixed-methods study involving analysis of routinely collected programme data followed by key informant interviews (KIIs) with 32 health care providers. From October 2016 to March 2017, of the 2,331 eligible patients, 1,066 (46%) had not undergone Xpert-MTB/Rif testing. Patients from townships without Xpert-MTB/Rif testing facilities, new TB patients, patients whose HIV status was negative or unknown and extra pulmonary TB patients were less likely to undergo Xpert-MTB/Rif testing. From the health care providers’ perspective, the most common reasons for non-testing were: (a) lack of awareness of the eligibility criteria; (b) difficulties in collecting sputum and transportation from eligible patients to the testing sites. We conclude that nearly half of eligible patients were not tested for RR-TB. Training of health care providers about the latest eligibility criteria and improvement in sputum collection and transportation systems particularly for townships without Xpert-MTB/Rif testing facilities are required to improve RR-TB testing.
Functional duplication of Rap1 in methylotrophic yeasts
Authors: Malyavko Alexander N. , Petrova Olga A. , Zvereva Maria I. , Dontsova Olga A. 
Published: May 2019

AbstractThe telomere regulator and transcription factor Rap1 is the only telomere protein conserved in yeasts and mammals. Its functional repertoire in budding yeasts is a particularly interesting field for investigation, given the high evolutionary diversity of this group of unicellular organisms. In the methylotrophic thermotolerant speciesHansenula polymorphaDL-1 the RAP1 gene is duplicated (HpRAP1A and HpRAP1B). Here, we report the functional characterization of the two paralogues fromH.polymorphaDL-1. We uncover distinct (but overlapping) DNA binding preferences of HpRap1A and HpRap1B proteins. We show that only HpRap1B is able to recognize telomeric DNA directly and to protect it from excessive recombination, whereas HpRap1A is associated with subtelomere regions. Furthermore, we identify specific binding sites for both HpRap1A and HpRap1B within promoters of a large number of ribosomal protein genes (RPGs), implicating Rap1 in the control of the RP regulon inH.polymorpha. Our bioinformatic analysis suggests that RAP1 was duplicated early in the evolution of the “methylotrophs” clade, and the two genes evolved independently. Therefore, our characterization of Rap1 paralogues inH.polymorphamay be relevant to other “methylotrophs”, yielding valuable insights into the evolution of budding yeasts.
Statistical Properties and Predictability of Extreme Epileptic Events
Authors: Frolov Nikita S. , Grubov Vadim V. , Maksimenko Vladimir A. , Lüttjohann Annika , Makarov Vladimir V. , Pavlov Alexey N. , Sitnikova Evgenia , Pisarchik Alexander N. , Kurths Jürgen , Hramov Alexander E. 
Published: May 2019

AbstractThe use of extreme events theory for the analysis of spontaneous epileptic brain activity is a relevant multidisciplinary problem. It allows deeper understanding of pathological brain functioning and unraveling mechanisms underlying the epileptic seizure emergence along with its predictability. The latter is a desired goal in epileptology which might open the way for new therapies to control and prevent epileptic attacks. With this goal in mind, we applied the extreme event theory for studying statistical properties of electroencephalographic (EEG) recordings of WAG/Rij rats with genetic predisposition to absence epilepsy. Our approach allowed us to reveal extreme events inherent in this pathological spiking activity, highly pronounced in a particular frequency range. The return interval analysis showed that the epileptic seizures exhibit a highly-structural behavior during the active phase of the spiking activity. Obtained results evidenced a possibility for early (up to 7 s) prediction of epileptic seizures based on consideration of EEG statistical properties.
Metamaterial emitter for thermophotovoltaics stable up to 1400 °C
Authors: Chirumamilla Manohar , Krishnamurthy Gnanavel Vaidhyanathan , Knopp Katrin , Krekeler Tobias , Graf Matthias , Jalas Dirk , Ritter Martin , Störmer Michael , Petrov Alexander Yu , Eich Manfred 
Published: May 2019

AbstractHigh temperature stable selective emitters can significantly increase efficiency and radiative power in thermophotovoltaic (TPV) systems. However, optical properties of structured emitters reported so far degrade at temperatures approaching 1200 °C due to various degradation mechanisms. We have realized a 1D structured emitter based on a sputtered W-HfO2 layered metamaterial and demonstrated desired band edge spectral properties at 1400 °C. To the best of our knowledge the temperature of 1400 °C is the highest reported for a structured emitter, so far. The spatial confinement and absence of edges stabilizes the W-HfO2 multilayer system to temperatures unprecedented for other nanoscaled W-structures. Only when this confinement is broken W starts to show the well-known self-diffusion behavior transforming to spherical shaped W-islands. We further show that the oxidation of W by atmospheric oxygen could be prevented by reducing the vacuum pressure below 10−5 mbar. When oxidation is mitigated we observe that the 20 nm spatially confined W films survive temperatures up to 1400 °C. The demonstrated thermal stability is limited by grain growth in HfO2, which leads to a rupture of the W-layers, thus, to a degradation of the multilayer system at 1450 °C.
A Systematic Review of the Clinical Efficacy and Safety of CFTR Modulators in Cystic Fibrosis
Authors: Habib Al-Rahim R. , Kajbafzadeh Majid , Desai Sameer , Yang Connie L. , Skolnik Kate , Quon Bradley S. 
Published: May 2019

AbstractSeveral placebo-controlled trials have been recently published evaluating novel therapies targeting the defective CFTR protein. This systematic review examines the clinical efficacy and safety of CFTR modulators in individuals with cystic fibrosis (CF) with specific genetic mutations. Online sources were searched for placebo-controlled, parallel-design clinical trials investigating CFTR modulators from January 1, 2005 to March 31, 2018. The primary outcome of interest was FEV1% predicted (ppFEV1). Fourteen RCTs met our eligibility criteria. The largest improvement in ppFEV1 favouring treatment was observed for ivacaftor (IVA) in G551D individuals (≥6 years old). Both tezacaftor-ivacaftor (TEZ-IVA) and lumacaftor-ivacaftor (LUM-IVA) also improved ppFEV1 in F508del homozygous individuals but there was increased reporting of respiratory adverse events with LUM-IVA compared to placebo. IVA also significantly improved ppFEV1 in a sub-group of individuals ≥18 years old with an R117H mutation. No significant improvements in ppFEV1 were observed for IVA, LUM, or TEZ in F508del homozygous individuals, LUM or LUM-IVA in F508del heterozygous individuals, or ataluren in individuals with a nonsense mutation. Significant improvements in ppFEV1 and other clinical outcomes were observed for IVA in G551D individuals, TEV-IVA and LUM-IVA in F508del homozygous individuals, and IVA in adults with a R117H mutation.
A convolutional neural network-based system to prevent patient misidentification in FDG-PET examinations
Authors: Kawauchi Keisuke , Hirata Kenji , Katoh Chietsugu , Ichikawa Seiya , Manabe Osamu , Kobayashi Kentaro , Watanabe Shiro , Furuya Sho , Shiga Tohru 
Published: May 2019

AbstractPatient misidentification in imaging examinations has become a serious problem in clinical settings. Such misidentification could be prevented if patient characteristics such as sex, age, and body weight could be predicted based on an image of the patient, with an alert issued when a mismatch between the predicted and actual patient characteristic is detected. Here, we tested a simple convolutional neural network (CNN)-based system that predicts patient sex from FDG PET-CT images. This retrospective study included 6,462 consecutive patients who underwent whole-body FDG PET-CT at our institute. The CNN system was used for classifying these patients by sex. Seventy percent of the randomly selected images were used to train and validate the system; the remaining 30% were used for testing. The training process was repeated five times to calculate the system’s accuracy. When images for the testing were given to the learned CNN model, the sex of 99% of the patients was correctly categorized. We then performed an image-masking simulation to investigate the body parts that are significant for patient classification. The image-masking simulation indicated the pelvic region as the most important feature for classification. Finally, we showed that the system was also able to predict age and body weight. Our findings demonstrate that a CNN-based system would be effective to predict the sex of patients, with or without age and body weight prediction, and thereby prevent patient misidentification in clinical settings.
Genetic inhibition of CRMP2 phosphorylation at serine 522 promotes axonal regeneration after optic nerve injury
Authors: Kondo Shunsuke , Takahashi Kazuya , Kinoshita Yuki , Nagai Jun , Wakatsuki Shuji , Araki Toshiyuki , Goshima Yoshio , Ohshima Toshio 
Published: May 2019

AbstractAxonal degeneration occurs in various neurological diseases and traumatic nerve injury, and axonal regeneration is restricted by inhibitory factors in the central nervous system. Cyclin-dependent kinase 5 and glycogen synthase kinase 3β (GSK3β) are activated by one of those inhibitors, and collapsin response mediator protein 2 (CRMP2) is phosphorylated by both kinases. We previously developed a CRMP2 knock-in (CRMP2 KI) mouse line, in which CRMP2 phosphorylation at Ser 522 is inhibited. Because CRMP2 KI mice showed promotion of axonal regeneration after spinal cord injury, we hypothesized that CRMP2 KI mice would show higher axonal regeneration after optic nerve injury. In this study, we first show that depolymerization of microtubules after optic nerve crush (ONC) injury was suppressed in CRMP2 KI mice. Loss of retinal ganglia cells was also reduced after ONC. We found that protein level of GAP43, a marker of regenerative axons, was higher in the optic nerve from CRMP2KI than that from wild type 4 weeks after of ONC. We further observed increased numbers of axons labeled by tracer in the optic nerve after ONC in CRMP2 KI mice. These results suggest that inhibition of phosphorylation of CRMP2 suppresses axonal degeneration and promotes axonal regeneration after optic nerve injury.
A phospholipase D2 inhibitor, CAY10594, ameliorates acetaminophen-induced acute liver injury by regulating the phosphorylated-GSK-3β/JNK axis
Authors: Lee Sung Kyun , Bae Geon Ho , Kim Ye Seon , Kim Hyung Sik , Lee Mingyu , Ghim Jaewang , Zabel Brian A. , Ryu Sung Ho , Bae Yoe-Sik 
Published: May 2019

AbstractWe examined the role of phospholipase D2 (PLD2) on acetaminophen (APAP)-induced acute liver injury using a PLD2 inhibitor (CAY10594). 500 mg/kg of APAP challenge caused acute liver damage. CAY10594 administration markedly blocked the acute liver injury in a dose-dependent manner, showing almost complete inhibition with 8 mg/kg of CAY10594. During the pathological progress of acute liver injury, GSH levels are decreased, and this is significantly recovered upon the administration of CAY10594 at 6 hours post APAP challenge. GSK-3β (Serine 9)/JNK phosphorylation is mainly involved in APAP-induced liver injury. CAY10594 administration strongly blocked GSK-3β (Serine 9)/JNK phosphorylation in the APAP-induced acute liver injury model. Consistently, sustained JNK activation in the cytosol and mitochondria from hepatocytes were also decreased in CAY10594-treated mice. Many types of immune cells are also implicated in APAP-induced liver injury. However, neutrophil and monocyte populations were not different between vehicle- and CAY10594-administered mice which are challenged with APAP. Therapeutic administration of CAY10594 also significantly attenuated liver damage caused by the APAP challenge, eliciting an enhanced survival rate. Taken together, these results indicate that PLD2 is involved in the intrinsic response pathway of hepatocytes driving the pathogenesis of APAP-induced acute liver injury, and PLD2 may therefore represent an important therapeutic target for patients with drug-induced liver injury.
Transducin activates cGMP phosphodiesterase by trapping inhibitory γ subunit freed reversibly from the catalytic subunit in solution
Authors: Asano Teizo , Kawamura Satoru , Tachibanaki Shuji 
Published: May 2019

AbstractActivation of cGMP phosphodiesterase (PDE) by activated transducin α subunit (Tα*) is a necessary step to generate a light response in vertebrate photoreceptors. PDE in rods is a heterotetramer composed of two catalytic subunits, PDEα and PDEβ, and two inhibitory PDEγ subunits, each binding to PDEα or PDEβ. Activation of PDE is achieved by relief of the inhibitory constraint of PDEγ on the catalytic subunit. In this activation mechanism, it is widely believed that Tα* binds to PDEγ still bound to the catalytic subunit, and removes or displaces PDEγ from the catalytic subunit. However, recent structural analysis showed that the binding of Tα* to PDEγ still bound to PDEα or PDEβ seems to be difficult because the binding site of PDEγ to PDEα or PDEβ overlaps with the binding site to Tα*. In the present study, we propose a novel activation mechanism of PDE, the trapping mechanism, in which Tα* activates PDE by trapping PDEγ released reversibly and spontaneously from the catalytic subunit. This mechanism well explains PDE activation by Tα* in solution. Our further analysis with this mechanism suggests that more effective PDE activation in disk membranes is highly dependent on the membrane environment.
Visualization of unstained DNA nanostructures with advanced in-focus phase contrast TEM techniques
Authors: Kabiri Yoones , Ravelli Raimond B. G. , Lehnert Tibor , Qi Haoyuan , Katan Allard J. , Roest Natascha , Kaiser Ute , Dekker Cees , Peters Peter J. , Zandbergen Henny 
Published: May 2019

AbstractOver the last few years, tremendous progress has been made in visualizing biologically important macromolecules using transmission electron microscopy (TEM) and understanding their structure-function relation. Yet, despite the importance of DNA in all forms of life, TEM visualization of individual DNA molecules in its native unlabeled form has remained extremely challenging. Here, we present high-contrast images of unstained single-layer DNA nanostructures that were obtained using advanced in-focus phase contrast TEM techniques. These include sub-Ångstrom low voltage electron microscopy (SALVE), the use of a volta-potential phase plate (VPP), and dark-field (DF) microscopy. We discuss the advantages and drawbacks of these techniques for broad applications in structural biology and materials science.
miR-494 induces EndMT and promotes the development of HCC (Hepatocellular Carcinoma) by targeting SIRT3/TGF-β/SMAD signaling pathway
Authors: Zhang Jinqian , Zhu Yan , Hu Liangshan , Yan Fang , Chen Jinglong 
Published: May 2019

AbstractEndMT has an important effect on metastasis and progression of tumor. This work will elucidate the effect of miR-494 on EndMT and development of HCC. Therefore, the differential miRNA expression among non-tumorous, para-tumorous and tumorous tissues was analyzed. Moreover, luciferase activities of SIRT3 3′UTR treated with miR-494 were determined. Then human hepatoma cell lines were dealt with mimics or inhibitors of miR-494, migration and proliferation ability were assessed. The expression of SIRT3 and markers of mesenchymal cell were analyzed. The influences of miR-494 on development of HCC through inducing EndMT by targeting SIRT3 and TGF-β/SMAD signaling pathways in hepatoma cell lines were investigated. Xenograft mice were used to explore the potential roles of miR-494 on EndMT and development of HCC in vivo. Our results showed that, compared with non-tumorous tissues, 17 miRNAs were upregulated and 3 miRNAs were down-regulated in tumor tissues. In tumor tissues, the miR-494 expression level was much more than the expression of para-tumorous and non-tumorous tissues. MiR-494 suppressed SIRT3 expression, additionally enhanced expression of mesenchymal cell markers, while exerted effects on cell proliferation and migration of hepatoma cell lines. Moreover, the antagomir of miR-494 could protect against development process in xenogarft murine model. In conclusions, our work demonstrated that miR-494 targeted to SIRT3, and was a crucial mediator of EndMT and development of HCC through regulating SIRT3/TGF-β/SMAD signaling pathway. It suggested that aim at SIRT3/TGF-β/SMAD signaling pathway through suppressing the miR-494 expression level, was a feasible therapy strategy for HCC.
Attenuated NoGo-related beta desynchronisation and synchronisation in Parkinson’s disease revealed by magnetoencephalographic recording
Authors: Wu Hung-Ming , Hsiao Fu-Jung , Chen Rou-Shayn , Shan Din-E , Hsu Wan-Yu , Chiang Ming-Chang , Lin Yung-Yang 
Published: May 2019

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterised by motor abnormalities. Many non-demented patients with PD have cognitive impairment especially in executive functions. Using magnetoencephalographic (MEG) recording combined with event-related desynchronisation/synchronisation (ERD/ERS) analysis, we investigated cortical executive functions during a Go/NoGo task in PD patients and matched healthy subjects. PD patients had a longer reaction time in the Go condition and had a higher error ratio in both Go and NoGo conditions. The MEG analysis showed that the PD patients had a significant reduction in beta ERD during the NoGo condition and in beta ERS during both Go and NoGo conditions compared with the healthy subjects (all p < 0.05). Moreover, in the Go condition, the onsets of beta ERD and ERS were delayed in PD patients. Notably, NoGo ERS was negatively correlated with the Unified Parkinson’s Disease Rating Scale (UPDRS) score in PD patients. The present study demonstrated abnormalities in motor programming, response inhibition, and frontal inhibitory modulation in PD. Further extensive investigations are necessary to confirm the longitudinal treatment responses in PD.