bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Alboran volcanic-arc modulated the Messinian faunal exchange and salinity crisis
Authors: Booth-Rea Guillermo , R. Ranero César , Grevemeyer Ingo 
Published: August 2018

AbstractWhat process triggered the Mediterranean Sea restriction remains debated since the discovery of the Messinian Salinity Crisis (MSC). Recent hypotheses infer that the MSC initiated after the closure of the Atlantic-Mediterranean Betic and Rifean corridors, being modulated through restriction at the Gibraltar Strait. These hypotheses however, do not integrate contemporaneous speciation patterns of the faunal exchange between Iberia and Africa and several geological features like the evaporite distribution. Exchange of terrestrial biota occurred before, during and after the MSC, and speciation models support an exchange path across the East Alborán basin (EAB) located a few hundreds of km east of the Gibraltar Strait. Yet, a structure explaining jointly geological and biological observations has remained undiscovered. We present new seismic data showing the velocity structure of a well-differentiated 14–17-km thick volcanic arc in the EAB. Isostatic considerations support that the arc-crust buoyancy created an archipelago leading to a filter bridge across the EAB. Sub-aerial erosional unconformities and onlap relationships support that the arc was active between ~10–6 Ma. Progressive arc build-up leading to an archipelago and its later subsidence can explain the extended exchange of terrestrial biota between Iberia and Africa (~7–3 Ma), and agrees with patterns of biota speciation and terrestrial fossil distribution before the MSC (10–6.2 Ma). In this scenario, the West Alboran Basin (WAB) could then be the long-postulated open-marine refuge for the Mediterranean taxa that repopulated the Mediterranean after the MSC, connected to the deep restricted Mediterranean basin through a sill at the Alboran volcanic arc archipelago.
Rapid and simple detection of Tamiflu-resistant influenza virus: Development of oseltamivir derivative-based lateral flow biosensor for point-of-care (POC) diagnostics
Authors: Hwang Seul Gee , Ha Kab , Guk Kyeonghye , Lee Do Kyung , Eom Gayoung , Song Sinae , Kang Taejoon , Park Hwangseo , Jung Juyeon , Lim Eun-Kyung 
Published: August 2018

AbstractWe have developed a novel oseltamivir derivative (oseltamivir hexylthiol; OHT) that exhibits a higher binding affinity for Tamiflu-resistant virus (Tamiflu resistance) than for the wild-type virus (Tamiflu-susceptible virus; WT) as an antibody. First, OHT-modified gold nanoparticles (OHT-GNPs) are used in a simple colorimetric assay as nanoprobes for the Tamiflu-resistant virus. In the presence of Tamiflu-resistant virus, they show a colorimetric change from deep red to purple because of the OHT-GNP aggregation driven by strong interactions between OHT and neuraminidase (NA) on the surface of the Tamiflu-resistance. Moreover, the color gradually turns purple as the concentration of the Tamiflu-resistant virus increases, allowing the determination of the presence of the virus with the naked eye. Furthermore, an OHT-based lateral flow assay (LFA) has been developed as a rapid and easy detection device for Tamiflu resistance. It shows detection specificity for various virus concentrations of Tamiflu-resistant virus even for the mixture of WT and Tamiflu-resistant viruses, where the limit of detection (LOD) is 5 × 102 ~ 103 PFU per test (=1 × 104 PFU/mL). It has been confirmed that this platform can provide accurate information on whether a virus exhibits Tamiflu resistance, thus supporting the selection of appropriate treatments using point-of-care (POC) diagnostics.
The Ras-related gene ERAS is involved in human and murine breast cancer
Authors: Suárez-Cabrera Cristian , de la Peña Bárbara , González Laura L. , Page Angustias , Martínez-Fernández Mónica , Casanova M. Llanos , Paramio Jesús M. , Rojo-Sebastián Alejandro , Moreno-Bueno Gema , Maroto Alicia , Ramírez Ángel , Navarro Manuel 
Published: August 2018

AbstractAlthough Ras genes are frequently mutated in human tumors, these mutations are uncommon in breast cancer. However, many breast tumors show evidences of Ras pathway activation. In this manuscript, we have analyzed and characterized mouse mammary tumors generated by random Sleeping Beauty transposon mutagenesis and identify ERAS -a member of the RAS family silenced in adult tissues- as a new gene involved in progression and malignancy of breast cancer. Forced expression of ERAS in human non-transformed mammary gland cells induces a process of epithelial-to-mesenchymal transition and an increase in stem cells markers; these changes are mediated by miR-200c downregulation. ERAS expression in human tumorigenic mammary cells leads to the generation of larger and less differentiated tumors in xenotransplant experiments. Immunohistochemical, RT-qPCR and bioinformatics analysis of human samples show that ERAS is aberrantly expressed in 8–10% of breast tumors and this expression is associated with distant metastasis and reduced metastasis-free survival. In summary, our results reveal that inappropriate activation of ERAS may be important in the development of a subset of breast tumors. These findings open the possibility of new specific treatments for this subset of ERAS-expressing tumors.
Nexilin/NEXN controls actin polymerization in smooth muscle and is regulated by myocardin family coactivators and YAP
Authors: Zhu Baoyi , Rippe Catarina , Holmberg Johan , Zeng Shaohua , Perisic Ljubica , Albinsson Sebastian , Hedin Ulf , Uvelius Bengt , Swärd Karl 
Published: August 2018

AbstractNexilin, encoded by the NEXN gene, is expressed in striated muscle and localizes to Z-discs, influencing mechanical stability. We examined Nexilin/NEXN in smooth muscle cells (SMCs), and addressed if Nexilin localizes to dense bodies and dense bands and whether it is regulated by actin-controlled coactivators from the MRTF (MYOCD, MKL1, MKL2) and YAP/TAZ (YAP1 and WWTR1) families. NEXN expression in SMCs was comparable to that in striated muscles. Immunofluorescence and immunoelectron microscopy suggested that Nexilin localizes to dense bodies and dense bands. Correlations at the mRNA level suggested that NEXN expression might be controlled by actin polymerization. Depolymerization of actin using Latrunculin B repressed the NEXN mRNA and protein in bladder and coronary artery SMCs. Overexpression and knockdown supported involvement of both YAP/TAZ and MRTFs in the transcriptional control of NEXN. YAP/TAZ and MRTFs appeared equally important in bladder SMCs, whereas MRTFs dominated in vascular SMCs. Expression of NEXN was moreover reduced in situations of SMC phenotypic modulation in vivo. The proximal promoter of NEXN conferred control by MRTF-A/MKL1 and MYOCD. NEXN silencing reduced actin polymerization and cell migration, as well as SMC marker expression. NEXN targeting by actin-controlled coactivators thus amplifies SMC differentiation through the actin cytoskeleton, probably via dense bodies and dense bands.
A gene-rich fraction analysis of the Passiflora edulis genome reveals highly conserved microsyntenic regions with two related Malpighiales species
Authors: Munhoz Carla Freitas , Costa Zirlane Portugal , Cauz-Santos Luiz Augusto , Reátegui Alina Carmen Egoávil , Rodde Nathalie , Cauet Stéphane , Dornelas Marcelo Carnier , Leroy Philippe , Varani Alessandro de Mello , Bergès Hélène , Vieira Maria Lucia Carneiro 
Published: August 2018

AbstractPassiflora edulis is the most widely cultivated species of passionflowers, cropped mainly for industrialized juice production and fresh fruit consumption. Despite its commercial importance, little is known about the genome structure of P. edulis. To fill in this gap in our knowledge, a genomic library was built, and now completely sequenced over 100 large-inserts. Sequencing data were assembled from long sequence reads, and structural sequence annotation resulted in the prediction of about 1,900 genes, providing data for subsequent functional analysis. The richness of repetitive elements was also evaluated. Microsyntenic regions of P. edulis common to Populus trichocarpa and Manihot esculenta, two related Malpighiales species with available fully sequenced genomes were examined. Overall, gene order was well conserved, with some disruptions of collinearity identified as rearrangements, such as inversion and translocation events. The microsynteny level observed between the P. edulis sequences and the compared genomes is surprising, given the long divergence time that separates them from the common ancestor. P. edulis gene-rich segments are more compact than those of the other two species, even though its genome is much larger. This study provides a first accurate gene set for P. edulis, opening the way for new studies on the evolutionary issues in Malpighiales genomes.
Unsupervised Medical Image Segmentation Based on the Local Center of Mass
Authors: Aganj Iman , Harisinghani Mukesh G. , Weissleder Ralph , Fischl Bruce 
Published: August 2018

AbstractImage segmentation is a critical step in numerous medical imaging studies, which can be facilitated by automatic computational techniques. Supervised methods, although highly effective, require large training datasets of manually labeled images that are labor-intensive to produce. Unsupervised methods, on the contrary, can be used in the absence of training data to segment new images. We introduce a new approach to unsupervised image segmentation that is based on the computation of the local center of mass. We propose an efficient method to group the pixels of a one-dimensional signal, which we then use in an iterative algorithm for two- and three-dimensional image segmentation. We validate our method on a 2D X-ray image, a 3D abdominal magnetic resonance (MR) image and a dataset of 3D cardiovascular MR images.
Time-Series Analysis of Tumorigenesis in a Murine Skin Carcinogenesis Model
Authors: Aoto Yoshimasa , Okumura Kazuhiro , Hachiya Tsuyoshi , Hase Sumitaka , Wakabayashi Yuichi , Ishikawa Fuyuki , Sakakibara Yasubumi 
Published: August 2018

AbstractRecent years have witnessed substantial progress in understanding tumor heterogeneity and the process of tumor progression; however, the entire process of the transition of tumors from a benign to metastatic state remains poorly understood. In the present study, we performed a prospective cancer genome-sequencing analysis by employing an experimental carcinogenesis mouse model of squamous cell carcinoma to systematically understand the evolutionary process of tumors. We surgically collected a part of a lesion of each tumor and followed the progression of these tumors in vivo over time. Comparative time-series analysis of the genomes of tumors with different fates, i.e., those that eventually metastasized and regressed, suggested that these tumors acquired and inherited different mutations. These findings suggest that despite the occurrence of an intra-tumor selection event for malignant alteration during the transformation from early- to late-stage papilloma, the fate determination of tumors might be determined at an even earlier stage.
Redox state affects fecundity and insecticide susceptibility in Anopheles gambiae
Authors: Champion Cody J. , Xu Jiannong 
Published: August 2018

AbstractRedox reactions play a central role in the metabolism of an organism. It is vital to maintain redox homeostasis in response to the fluctuation of redox shift in various biological contexts. NADPH-dependent reducing capacity is one of the key factors contributing to the redox homeostasis. To understand the redox capacity and its impact on mosquito fecundity and susceptibility to insecticides in Anopheles gambiae, we examined the dynamics of elevated oxidative state via induction by paraquat (PQ) and the inhibition of NADPH regeneration by 6-aminonicotinamide (6AN). In naïve conditions, inherent oxidative capacity varies between individuals, as measured by GSSG/GSH ratio. The high GSSG/GSH ratio was negatively correlated with fecundity. Both PQ and 6AN feeding increased GSSG/GSH ratio and elevated protein carbonylation, a marker of oxidative damage. Both pro-oxidants lowered egg production. Co-feeding the pro-oxidants with antioxidant lycopene attenuated the adverse effects on fecundity, implying that oxidative stress was the cause of this phenotype. Pre-feeding with 6AN increased insecticide susceptibility in DDT resistant mosquitoes. These results indicate that oxidative state is delicate in mosquitoes, manipulation of NADPH pool may adversely affect fecundity and insecticide detoxification capacity. This knowledge can be exploited to develop novel vector control strategies targeting fecundity and insecticide resistance.
The invasiveness of human cervical cancer associated to the function of NaV1.6 channels is mediated by MMP-2 activity
Authors: Lopez-Charcas Osbaldo , Espinosa Ana Maria , Alfaro Ana , Herrera-Carrillo Zazil , Ramirez-Cordero Belen Ernestina , Cortes-Reynosa Pedro , Perez Salazar Eduardo , Berumen Jaime , Gomora Juan Carlos 
Published: August 2018

AbstractVoltage-gated sodium (NaV) channels have been related with cell migration and invasiveness in human cancers. We previously reported the contribution of NaV1.6 channels activity with the invasion capacity of cervical cancer (CeCa) positive to Human Papilloma Virus type 16 (HPV16), which accounts for 50% of all CeCa cases. Here, we show that NaV1.6 gene (SCN8A) overexpression is a general characteristic of CeCa, regardless of the HPV type. In contrast, no differences were observed in NaV1.6 channel expression between samples of non-cancerous and cervical intraepithelial neoplasia. Additionally, we found that CeCa cell lines, C33A, SiHa, CaSki and HeLa, express mainly the splice variant of SCN8A that lacks exon 18, shown to encode for an intracellularly localized NaV1.6 channel, whereas the full-length adult form was present in CeCa biopsies. Correlatively, patch-clamp experiments showed no evidence of whole-cell sodium currents (INa) in CeCa cell lines. Heterologous expression of full-length NaV1.6 isoform in C33A cells produced INa, which were sufficient to significantly increase invasion capacity and matrix metalloproteinase type 2 (MMP-2) activity. These data suggest that upregulation of NaV1.6 channel expression occurs when cervical epithelium have been transformed into cancer cells, and that NaV1.6-mediated invasiveness of CeCa cells involves MMP-2 activity. Thus, our findings support the notion about using NaV channels as therapeutic targets against cancer metastasis.
Identification of Magnesium Oxychloride Cement Biomaterial Heterogeneity using Raman Chemical Mapping and NIR Hyperspectral Chemical Imaging
Authors: Dorrepaal Ronan M. , Gowen Aoife A. 
Published: August 2018

AbstractThe present study investigated spatial heterogeneity in magnesium oxychloride cements within a model of a mould using hyperspectral chemical imaging (HCI). The ability to inspect cements within a mould allows for the assessment of material formation in real time in addition to factors affecting ultimate material formation. Both macro scale NIR HCI and micro scale pixel-wise Raman chemical mapping were employed to characterise the same specimens. NIR imaging is rapid, however spectra are often convoluted through the overlapping of overtone peaks, which can make interpretation difficult. Raman spectra are more easily interpretable, however Raman imaging can suffer from slower acquisition times, particularly when the signal to noise ratio is relatively poor and the spatial resolution is high. To overcome the limitations of both, Raman/NIR data fusion techniques were explored and implemented. Spectra collected using both modalities were co-registered and intra and inter-modality peak correlations were investigated while k-means cluster patterns were compared. In addition, partial least squares regression models, built using NIR spectra, predicted chemical-identifying Raman peaks with an R2 of up to >0.98. As macro scale imaging presented greater data collection speeds, chemical prediction maps were built using NIR HCIs.
3D cephalometric analysis using Magnetic Resonance Imaging: validation of accuracy and reproducibility
Authors: Juerchott Alexander , Saleem Muhammad Abdullah , Hilgenfeld Tim , Freudlsperger Christian , Zingler Sebastian , Lux Christopher J. , Bendszus Martin , Heiland Sabine 
Published: August 2018

AbstractThe aim of this study was to validate geometric accuracy and in vivo reproducibility of landmark-based cephalometric measurements using high-resolution 3D Magnetic Resonance Imaging (MRI) at 3 Tesla. For accuracy validation, 96 angular and 96 linear measurements were taken on a phantom in 3 different positions. In vivo MRI scans were performed on 3 volunteers in five head positions. For each in vivo scan, 27 landmarks were determined from which 19 angles and 26 distances were calculated. Statistical analysis was performed using Bland-Altman analysis, the two one-sided tests procedure and repeated measures one-way analysis of variance. In comparison to ground truth, all MRI-based phantom measurements showed statistical equivalence (p < 0.001) and an excellent agreement in Bland-Altman analysis (bias ranges: −0.090–0.044°, −0.220–0.241 mm). In vivo cephalometric analysis was highly reproducible among the five different head positions in all study participants, without statistical differences for all angles and distances (p > 0.05). Ranges between maximum and minimum in vivo values were consistently smaller than 2° and 2 mm, respectively (average ranges: 0.88°/0.87 mm). In conclusion, this study demonstrates that accurate and reproducible 3D cephalometric analysis can be performed without exposure to ionizing radiation using MRI.
Microparticles from β-thalassaemia/HbE patients induce endothelial cell dysfunction
Authors: Kheansaard Wasinee , Phongpao Kunwadee , Paiboonsukwong Kittiphong , Pattanapanyasat Kovit , Chaichompoo Pornthip , Svasti Saovaros 
Published: August 2018

AbstractThromboembolic complication occurs frequently in β-thalassaemia/HbE patients, particularly in splenectomised patients. Endothelial cells play an important role in thrombosis. There is strong evidence of endothelial cell activation and dysfunction in β-thalassaemia. Microparticles (MPs) are associated with thrombosis and endothelial cell dysfunction in many diseases including β-thalassaemia. However, the effect of thalassaemic-MPs on endothelial cells mediating thrombus formation has not been elucidated. In this study, the effects of circulating MPs from β-thalassaemia/HbE patients on endothelial cell functions were investigated. The results showed that MPs directly induce tissue factor, interleukin (IL)-6, IL-8, intracellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin expression in human umbilical vein endothelial cells (HUVECs). Notably, the levels of these endothelial cell activation markers were significantly increased in HUVECs treated with MPs obtained from splenectomised β-thalassaemia/HbE patients when compared to MPs from non-splenectomised patients or normal subjects. The increased endothelial cell activation ultimately lead to increased monocyte-endothelial cell adhesion. THP-1 and HUVECs adhesion induced by MPs from normal subjects, non-splenectomised and splenectomised patients increased to 2.0 ± 0.4, 2.3 ± 0.4 and 3.8 ± 0.4 fold, respectively when compared to untreated cells. This finding suggests that MPs play an important role on thrombosis and vascular dysfunction in β-thalassaemia/HbE disease, especially in splenectomised cases.
Genetic and animal model analyses reveal the pathogenic role of a novel deletion of RELN in schizophrenia
Authors: Sobue Akira , Kushima Itaru , Nagai Taku , Shan Wei , Kohno Takao , Aleksic Branko , Aoyama Yuki , Mori Daisuke , Arioka Yuko , Kawano Naoko , Yamamoto Maeri , Hattori Mitsuharu , Nabeshima Toshitaka , Yamada Kiyofumi , Ozaki Norio 
Published: August 2018

AbstractReelin protein (RELN), an extracellular matrix protein, plays multiple roles that range from embryonic neuronal migration to spine formation in the adult brain. Results from genetic studies have suggested that RELN is associated with the risk of psychiatric disorders, including schizophrenia (SCZ). We previously identified a novel exonic deletion of RELN in a patient with SCZ. High-resolution copy number variation analysis revealed that this deletion included exons 52 to 58, which truncated the RELN in a similar manner to the Reln Orleans mutation (Relnrl-Orl). We examined the clinical features of this patient and confirmed a decreased serum level of RELN. To elucidate the pathophysiological role of the exonic deletion of RELN in SCZ, we conducted behavioral and neurochemical analyses using heterozygous Relnrl-Orl/+ mice. These mice exhibited abnormalities in anxiety, social behavior, and motor learning; the deficits in motor learning were ameliorated by antipsychotics. Methamphetamine-induced hyperactivity and dopamine release were significantly reduced in the Relnrl-Orl/+ mice. In addition, the levels of GABAergic markers were decreased in the brain of these mice. Taken together, our results suggest that the exonic deletion of RELN plays a pathological role, implicating functional changes in the dopaminergic and GABAergic systems, in the pathophysiology of SCZ.
A Novel Non-contact Heart Rate Monitor Using Impulse-Radio Ultra-Wideband (IR-UWB) Radar Technology
Authors: Lee Yonggu , Park Jun-Young , Choi Yeon-Woo , Park Hyun-Kyung , Cho Seok-Hyun , Cho Sung Ho , Lim Young-Hyo 
Published: August 2018

AbstractWe discovered that impulse-radio ultra-wideband (IR-UWB) radar could recognize cardiac motions in a non-contact fashion. Therefore, we measured the heart rate (HR) and rhythms using an IR-UWB radar sensor and evaluated the validity and reliability of the measurements in comparison to electrocardiography. The heart beats were measured in 6 healthy volunteers (18 samples) with normal sinus rhythm (NSR) and 16 patients (36 samples) with atrial fibrillation (AF) using both an IR-UWB radar sensor and electrocardiography simultaneously. The participants hold their breath for 20 seconds during the data acquisition. In subjects with NSR, there was excellent agreement of HR (intraclass correlation coefficient [ICC] 0.856), average R-R interval (ICC 0.997) and individual R-R intervals between the two methods (ICC 0.803). In subjects with AF, HR (ICC 0.871) and average R-R interval (ICC 0.925) from the radar sensor also agreed well with those from electrocardiography, though there was a small disagreement in the individual R-R intervals between the two methods (ICC 0.697). The rhythms computed by the signal-processing algorithm showed good agreement between the two methods (Cohen’s Kappa 0.922). The IR-UWB radar sensor is precise and accurate for assessing HR and rhythms in a non-contact fashion.
Rhythmogenesis evolves as a consequence of long-term plasticity of inhibitory synapses
Authors: Soloduchin Sarit , Shamir Maoz 
Published: August 2018

AbstractBrain rhythms are widely believed to reflect numerous cognitive processes. Changes in rhythmicity have been associated with pathological states. However, the mechanism underlying these rhythms remains unknown. Here, we present a theoretical analysis of the evolvement of rhythm generating capabilities in neuronal circuits. We tested the hypothesis that brain rhythms can be acquired via an intrinsic unsupervised learning process of activity dependent plasticity. Specifically, we focused on spike timing dependent plasticity (STDP) of inhibitory synapses. We detail how rhythmicity can develop via STDP under certain conditions that serve as a natural prediction of the hypothesis. We show how global features of the STDP rule govern and stabilize the resultant rhythmic activity. Finally, we demonstrate how rhythmicity is retained even in the face of synaptic variability. This study suggests a role for inhibitory plasticity that is beyond homeostatic processes.