bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-D monoclonal antibodies from 23 human and rodent cell lines display diverse IgG Fc-glycosylation profiles that determine their clinical efficacy
Authors: Kumpel Belinda M. , Saldova Radka , Koeleman Carolien A. M. , Abrahams Jodie L. , Ederveen Agnes Hipgrave , Armour Kathryn L. , Olovnikova Natalia I. , Vidarsson Gestur , Kapur Rick , Rudd Pauline M. , Wuhrer Manfred
Published: January 2020

Anti-D immunoglobulin (Anti-D Ig) prophylaxis prevents haemolytic disease of the fetus and newborn. Monoclonal IgG anti-Ds (mAb-Ds) would enable unlimited supplies but have differed in efficacy in FcγRIIIa-mediated ADCC assays and clinical trials. Structural variations of the oligosaccharide chains of mAb-Ds are hypothesised to be responsible. Quantitative data on 12 Fc-glycosylation features of 23 mAb-Ds (12 clones, 5 produced from multiple cell lines) and one blood donor-derived anti-D Ig were obtained by HPLC and mass spectrometry using 3 methods. Glycosylation of mAb-Ds from human B-lymphoblastoid cell lines (B) was similar to anti-D Ig although fucosylation varied, affecting ADCC activity.In vivo, two B mAb-Ds with 77–81% fucosylation cleared red cells and prevented D-immunisation but less effectively than anti-D Ig. High fucosylation (>89%) of mouse-human heterohybridoma (HH) and Chinese hamster ovary (CHO) mAb-Ds blocked ADCC and clearance. Rat YB2/0 mAb-Ds with <50% fucosylation mediated more efficient ADCC and clearance than anti-D Ig. Galactosylation of B mAb-Ds was 57–83% but 15–58% for rodent mAb-Ds. HH mAb-Ds had non-human sugars. These data reveal high galactosylation like anti-D Ig (>60%) together with lower fucosylation (<60%) as safe features of mAb-Ds for mediating rapid red cell clearance at low doses, to enable effective, inexpensive prophylaxis.
Iodinated Polyesters with Enhanced X-ray Contrast Properties for Biomedical Imaging
Authors: Lex Timothy R. , Brummel Beau R. , Attia Mohamed F. , Giambalvo Lauren N. , Lee Kinsey G. , Van Horn Brooke A. , Whitehead Daniel. C. , Alexis Frank
Published: January 2020

Synthetic materials exhibiting contrast imaging properties have become vital to the field of biomedical imaging. However, polymeric biomaterials are lacking imaging contrast properties for deep tissue imaging. This report details the synthesis and characterization of a suite of aryl-iodo monomers, which were used to prepare iodinated polyesters using a pre-functionalization approach. Commercially available 4-iodo-phenylalanine or 4-iodobenzyl bromide served as the starting materials for the synthesis of three iodinated monomeric moieties (a modified lactide, morpholine-2,5-dione, and caprolactone), which under a tin-mediated ring-opening polymerization (ROP), generated their respective polyesters (PE) or poly(ester amides) (PEA). An increase in X-ray intensity of all synthesized iodine-containing polymers, in comparison to non-iodinated poly(lactic acid) (PLA), validated their functionality as radio-opaque materials. The iodinated-poly(lactic acid) (iPLA) material was visualized through varying thicknesses of chicken tissue, thus demonstrating its potenial as a radio-opaque biomaterial.
Computer simulation study of the penetration of pulsed 30, 60 and 90 GHz radiation into the human ear
Authors: Vilagosh Zoltan , Lajevardipour Alireza , Wood Andrew
Published: January 2020

There is increasing interest in applications which use the 30 to 90 GHz frequency range, including automotive radar, 5 G cellular networks and wireless local area links. This study investigated pulsed 30–90 GHz radiation penetration into the human ear canal and tympanic membrane using computational phantoms. Modelling involved 100 ps and 20 ps pulsed excitation at three angles: direct (orthogonal), 30° anterior, and 45° superior to the ear canal. The incident power flux density (PD) estimation was normalised to the International Commission on Non-Ionizing Radiation Protection (1998) standard for general population exposure of 10 Wm−2 and occupational exposure of 50 Wm−2. The PD, specific absorption rate (SAR) and temperature rise within the tympanic membrane was highly dependent on the incident angle of the radiation and frequency. Using a 30 GHz pulse directed orthogonally into the ear canal, the PD in the tympanic membrane was 0.2% of the original maximal signal intensity. The corresponding PD at 90 GHz was 13.8%. A temperature rise of 0.032° C (+20%, −50%) was noted within the tympanic membrane using the equivalent of an occupational standard exposure at 90 GHz. The central area of the tympanic membrane is exposed in a preferential way and local effects on small regions cannot be excluded. The authors strongly advocate further research into the effects of radiation above 60 GHz on the structures of the ear to assist the process of setting standards.
Automatic vocal tract landmark localization from midsagittal MRI data
Authors: Eslami Mohammad , Neuschaefer-Rube Christiane , Serrurier Antoine
Published: January 2020

The various speech sounds of a language are obtained by varying the shape and position of the articulators surrounding the vocal tract. Analyzing their variations is crucial for understanding speech production, diagnosing speech disorders and planning therapy. Identifying key anatomical landmarks of these structures on medical images is a pre-requisite for any quantitative analysis and the rising amount of data generated in the field calls for an automatic solution. The challenge lies in the high inter- and intra-speaker variability, the mutual interaction between the articulators and the moderate quality of the images. This study addresses this issue for the first time and tackles it by means of Deep Learning. It proposes a dedicated network architecture named Flat-net and its performance are evaluated and compared with eleven state-of-the-art methods from the literature. The dataset contains midsagittal anatomical Magnetic Resonance Images for 9 speakers sustaining 62 articulations with 21 annotated anatomical landmarks per image. Results show that the Flat-net approach outperforms the former methods, leading to an overall Root Mean Square Error of 3.6 pixels/0.36 cm obtained in a leave-one-out procedure over the speakers. The implementation codes are also shared publicly on GitHub.
The critical role of glucose deprivation in epithelial-mesenchymal transition in hepatocellular carcinoma under hypoxia
Authors: Jo Hanhee , Lee Jongsook , Jeon Jeongyong , Kim Seon yoo , Chung Jee-in , Ko Hae yong , Lee Misu , Yun Mijin
Published: January 2020

Imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is used to determine sites of abnormal glucose metabolism to predict high tumor grade, metastasis, and poor patient survival. However, not all tumors with increased 18F-FDG uptake show aggressive tumor biology, as evident from the moderate correlation between metastasis and high FDG uptake. We hypothesized that metastasis is likely attributable to the complexity and heterogeneity of the cancer microenvironment. To identify the cancer microenvironment that induces the epithelial-mesenchymal transition (EMT) process, tumor areas of patients with HCC were analyzed by immunostaining. Our data demonstrated the induction of EMT process in HCC cells with low proliferation under hypoxic conditions. To validate our finding, among HCC cell lines, HepG2 cells with highly increased expression of HIF1α under hypoxia were employed in vitro and in vivo. Major changes in EMT-associated protein expression, such as the up-regulation of N-cadherin and snail/slug are associated with decreased proliferation-related protein (PCNA) caused by glucose deprivation under hypoxia. Indeed, PCNA knockdown-HepG2 cells under hypoxia showed the induction of more EMT process compare to the control. Thus, HCC cells with low proliferative potential under glucose-deprived and hypoxic conditions show high probability for induced EMT process and promote cell invasion. This study investigates reasons as to why an EMT process cannot fully be predicted. Our observations indicate that rather than analyzing a single factor, an integrated analysis of hypoxia with low glucose metabolism and low cell proliferation might be helpful to predict the potential impact on induction of EMT process and promotion of cell invasion.
Superconducting phase transitions in disordered NbTiN films
Authors: Burdastyh M. V. , Postolova S. V. , Proslier T. , Ustavshikov S. S. , Antonov A. V. , Vinokur V. M. , Mironov A. Yu.
Published: January 2020

Suppression of superconductivity in disordered systems is a fundamental problem of condensed matter physics. Here we investigate superconducting niobium-titanium-nitride (Nb1−xTixN) thin films grown by the atomic layer deposition (ALD) with slightly different growth process parameters. We observe a smooth crossover from the disorder-driven superconductor-normal metal transition (SMT) to the superconductor-insulator transition (SIT) via the intermediate Bose metal state detected by the low-temperature saturation of the temperature dependence of the sheet resistance. We demonstrate that the SIT via the intervening Bose metal state occurs if the sheet resistance of the film in the maximum, Rmax prior to the superconducting drop of R(T), exceeds Rq = h/4e2.
RNA Profiling Analysis of the Serum Exosomes Derived from Patients with Chronic Hepatitis and Acute-on-chronic Liver Failure Caused By HBV
Authors: Chen Jiajia , Xu Qingsheng , Zhang Yan , Zhang Huafen
Published: January 2020

Hepatitis B virus (HBV) is the main causative viral agent for liver diseases in China. In liver injury, exosomes may impede the interaction with chromatin in the target cell and transmit inflammatory, apoptosis, or regeneration signals through RNAs. Therefore, we attempted to determine the potential functions of exosomal RNAs using bioinformatics technology. We performed RNA sequencing analysis in exosomes derived from clinical specimens of healthy control (HC) individuals and patients with chronic hepatitis B (CHB) and acute-on-chronic liver failure caused by HBV (HBV-ACLF). This analysis resulted in the identification of different types and proportions of RNAs in exosomes from the HC individuals and patients. Exosomes from the CHB and HBV-ACLF patients showed distinct upregulation and downregulation patterns of differentially expressed genes compared with those from the HC subjects. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway analysis further confirmed different patterns of biological functions and signalling pathways in CHB and HBV-ACLF. Then we chose two upregulated RNAs both in CHB and HBV-ACLF for further qPCR validation. It confirmed the significantly different expression levels in CHB and HBV-ACLF compared with HC. Our findings indicate selective packaging of the RNA cargo into exosomes under different HBV attacks; these may represent potential targets for the diagnosis and treatment of HBV-caused liver injury.
Genome-scale data reveal the role of hybridization in lichen-forming fungi
Authors: Keuler Rachel , Garretson Alexis , Saunders Theresa , Erickson Robert J. , St. Andre Nathan , Grewe Felix , Smith Hayden , Lumbsch H. Thorsten , Huang Jen-Pan , St. Clair Larry L. , Leavitt Steven D.
Published: January 2020

Advancements in molecular genetics have revealed that hybridization may be common among plants, animals, and fungi, playing a role in evolutionary dynamics and speciation. While hybridization has been well-documented in pathogenic fungi, the effects of these processes on speciation in fungal lineages with different life histories and ecological niches are largely unexplored. Here we investigated the potential influence of hybridization on the emergence of morphologically and reproductively distinct asexual lichens. We focused on vagrant forms (growing obligately unattached to substrates) within a clade of rock-dwelling, sexually reproducing species in the Rhizoplaca melanophthalma (Lecanoraceae, Ascomycota) species complex. We used phylogenomic data from both mitochondrial and nuclear genomes to infer evolutionary relationships and potential patterns of introgression. We observed multiple instances of discordance between the mitochondrial and nuclear trees, including the clade comprising the asexual vagrant species R. arbuscula, R. haydenii, R. idahoensis, and a closely related rock-dwelling lineage. Despite well-supported phylogenies, we recovered strong evidence of a reticulated evolutionary history using a network approach that incorporates both incomplete lineage sorting and hybridization. These data suggest that the rock-dwelling western North American subalpine endemic R. shushanii is potentially the result of a hybrid speciation event, and introgression may have also played a role in other taxa, including vagrant species R. arbuscula, R. haydenii and R. idahoensis. We discuss the potential roles of hybridization in terms of generating asexuality and novel morphological traits in lichens. Furthermore, our results highlight the need for additional study of reticulate phylogenies when investigating species boundaries and evolutionary history, even in cases with well-supported topologies inferred from genome-scale data.
Gemcitabine induces Parkin-independent mitophagy through mitochondrial-resident E3 ligase MUL1-mediated stabilization of PINK1
Authors: Igarashi Ryoko , Yamashita Shun-ichi , Yamashita Tomohiro , Inoue Keiichi , Fukuda Tomoyuki , Fukuchi Takeo , Kanki Tomotake
Published: January 2020

Mitophagy plays an important role in the maintenance of mitochondrial homeostasis. PTEN-induced kinase (PINK1), a key regulator of mitophagy, is degraded constitutively under steady-state conditions. During mitophagy, it becomes stabilized in the outer mitochondrial membrane, particularly under mitochondrial stress conditions, such as in treatment with uncouplers, generation of excessive mitochondrial reactive oxygen species, and formation of protein aggregates in mitochondria. Stabilized PINK1 recruits and activates E3 ligases, such as Parkin and mitochondrial ubiquitin ligase (MUL1), to ubiquitinate mitochondrial proteins and induce ubiquitin-mediated mitophagy. Here, we found that the anticancer drug gemcitabine induces the stabilization of PINK1 and subsequent mitophagy, even in the absence of Parkin. We also found that gemcitabine-induced stabilization of PINK1 was not accompanied by mitochondrial depolarization. Interestingly, the stabilization of PINK1 was mediated by MUL1. These results suggest that gemcitabine induces mitophagy through MUL1-mediated stabilization of PINK1 on the mitochondrial membrane independently of mitochondrial depolarization.
Molecular level study of hot water extracted green tea buried in soils - a proxy for labile soil organic matter
Authors: Bell Nicholle G. A. , Smith Alan J. , Zhu Yufan , Beishuizen William H. , Chen Kangwei , Forster Dan , Ji Yiran , Knox Elizabeth A.
Published: January 2020

Understanding the composition of soil organic matter (SOM) is vital to our understanding of how soils form, evolve and respond to external stimuli. The shear complexity of SOM, an inseparable mixture of thousands of compounds hinders the determination of structure-function relationships required to explore these processes on a molecular level. Litter bags and soil hot water extracts (HWE) have frequently been used to study the transformation of labile SOM, however these are still too complex to examine beyond compound classes. In this work, a much simpler mixture, HWE buried green tea, was investigated by Nuclear Magnetic Resonance (NMR) spectroscopy and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR-MS), as a proxy for labile SOM. Changes induced by the burial over 90 days in a grassland, woodland and two peatland sites, one damaged by drainage and one undergoing restoration by drain-blocking, were analysed. Major differences between the extracts were observed on the level of compound classes, molecular formulae and specific molecules. The causes of these differences are discussed with reference to abiotic and biotic processes. Despite the vastly different detection limits of NMR and MS, chemometric analysis of the data yielded identical separation of the samples. These findings provide a basis for the molecular level interrogation of labile SOM and C-cycling processes in soils.
miRgo: integrating various off-the-shelf tools for identification of microRNA–target interactions by heterogeneous features and a novel evaluation indicator
Authors: Chu Yen-Wei , Chang Kai-Po , Chen Chi-Wei , Liang Yu-Tai , Soh Zhi Thong , Hsieh Li‐Ching
Published: January 2020

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and biological processes through binding to messenger RNAs. Predicting the relationship between miRNAs and their targets is crucial for research and clinical applications. Many tools have been developed to predict miRNA–target interactions, but variable results among the different prediction tools have caused confusion for users. To solve this problem, we developed miRgo, an application that integrates many of these tools. To train the prediction model, extreme values and median values from four different data combinations, which were obtained via an energy distribution function, were used to find the most representative dataset. Support vector machines were used to integrate 11 prediction tools, and numerous feature types used in these tools were classified into six categories—binding energy, scoring function, evolution evidence, binding type, sequence property, and structure—to simplify feature selection. In addition, a novel evaluation indicator, the Chu-Hsieh-Liang (CHL) index, was developed to improve the prediction power in positive data for feature selection. miRgo achieved better results than all other prediction tools in evaluation by an independent testing set and by its subset of functionally important genes. The tool is available at http://predictor.nchu.edu.tw/miRgo.
Methylenetetrahydrofolate reductase C677T polymorphism is not associated with the risk of nonsyndromic cleft lip/palate: An updated meta-analysis
Authors: Imani Mohammad Moslem , Golchin Negin , Safaei Mohsen , Rezaei Farzad , Abbasi Hooshyar , Sadeghi Masoud , Lopez-Jornet Pia , Mozaffari Hamid Reza , Sharifi Roohollah
Published: January 2020

Both genetic and environmental factors affect the risk of orofacial clefts. The present meta-analysis aimed to evaluate the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and risk of nonsyndromic cleft lip/palate (NSCL/P) in cases-control studies. The PubMed/Medline, Scopus, Web of Science, and Cochrane Library databases were searched up to April 2019 with no restrictions. The odds ratios (ORs) and 95% confidence intervals (CIs) in all analyses were calculated by Review Manager 5.3 software. The funnel plot analysis was carried out by the Comprehensive Meta-Analysis version 2.0 software. Subgroup analysis, meta-regression, and sensitivity analysis were performed for the pooled analyses. Thirty-one studies reviewed in this meta-analysis included 4710 NSCL/P patients and 7271 controls. There was no significant association between MTHFR C677T polymorphism and NSCL/P susceptibility related to allelic model (OR = 1.04; P = 0.49), homozygote model (OR = 1.11; P = 0.35), heterozygote model (OR = 0.99; P = 0.91), dominant model (OR = 1.00; P = 0.96), or recessive model (OR = 1.08; P = 0.23). There was no significant association between MTHFR C677T polymorphism and NSCL/P susceptibility based on the ethnicity or the source of cases. There was a significant linear relationship between the year of publication and log ORs for the allele model. The results of the present meta-analysis failed to show an association between MTHFR C677T polymorphism and NSCL/P susceptibility. The subgroup analyses based on the ethnicity and the source of cases further confirmed this result.
Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions
Authors: Thézénas Marie-Laëtitia , De Leo Bianca , Laux-Biehlmann Alexis , Bafligil Cemsel , Elger Bernd , Tapmeier Thomas , Morten Karl , Rahmioglu Nilufer , Dakin Stephanie G. , Charles Philip , Martinez Fernando Estrada , Steers Graham , Fischer Oliver M. , Mueller Joerg , Hess-Stumpp Holger , Steinmeyer Andreas , Manek Sanjiv , Zondervan Krina T. , Kennedy Stephen , Becker Christian M. , Shang Catherine , Zollner Thomas M. , Kessler Benedikt M. , Oppermann Udo
Published: January 2020

Endometriosis is a common gynaecological disease of women in reproductive age, and is thought to arise from retrograde menstruation and implantation of endometrial tissue, mostly into the peritoneal cavity. The condition is characterized by a chronic, unresolved inflammatory process thereby contributing to pain as cardinal symptom in endometriosis. Elevated reactive oxygen species (ROS) and oxidative stress have been postulated as factors in endometriosis pathogenesis. We here set out for a systematic study to identify novel mechanisms and pathways relating to oxidative stress in ectopic peritoneal lesions. Using combined proteomic and transcriptomic approaches, we identified novel targets including upregulated pro-oxidative enzymes, such as amine oxidase 3/vascular adhesion protein 1 (AOC3/VAP1) as well as downregulated protective factors, in particular alkenal reductase PTGR1 and methionine sulfoxide reductase. Consistent with an altered ROS landscape, we observed hemoglobin / iron overload, ROS production and lipid peroxidation in ectopic lesions. ROS-derived 4-hydroxy-2-nonenal induced interleukin IL-8 release from monocytes. Notably, AOC3 inhibitors provoked analgesic effects in inflammatory pain models in vivo, suggesting potential translational applicability.
Supramolecular tholos-like architecture constituted by archaeal proteins without functional annotation
Authors: Yagi-Utsumi Maho , Sikdar Arunima , Song Chihong , Park Jimin , Inoue Rintaro , Watanabe Hiroki , Burton-Smith Raymond N. , Kozai Toshiya , Suzuki Tatsuya , Kodama Atsuji , Ishii Kentaro , Yagi Hirokazu , Satoh Tadashi , Uchiyama Susumu , Uchihashi Takayuki , Joo Keehyoung , Lee Jooyoung , Sugiyama Masaaki , Murata Kazuyoshi , Kato Koichi
Published: January 2020

Euryarchaeal genomes encode proteasome-assembling chaperone homologs, PbaA and PbaB, although archaeal proteasome formation is a chaperone-independent process. Homotetrameric PbaB functions as a proteasome activator, while PbaA forms a homopentamer that does not interact with the proteasome. Notably, PbaA forms a complex with PF0014, an archaeal protein without functional annotation. In this study, based on our previous research on PbaA crystal structure, we performed an integrative analysis of the supramolecular structure of the PbaA/PF0014 complex using native mass spectrometry, solution scattering, high-speed atomic force microscopy, and electron microscopy. The results indicated that this highly thermostable complex constitutes ten PbaA and ten PF0014 molecules, which are assembled into a dumbbell-shaped structure. Two PbaA homopentameric rings correspond to the dumbbell plates, with their N-termini located outside of the plates and C-terminal segments left mobile. Furthermore, mutant PbaA lacking the mobile C-terminal segment retained the ability to form a complex with PF0014, allowing 3D modeling of the complex. The complex shows a five-column tholos-like architecture, in which each column comprises homodimeric PF0014, harboring a central cavity, which can potentially accommodate biomacromolecules including proteins. Our findings provide insight into the functional roles of Pba family proteins, offering a novel framework for designing functional protein cages.
5/6 nephrectomy induces different renal, cardiac and vascular consequences in 129/Sv and C57BL/6JRj mice
Authors: Hamzaoui Mouad , Djerada Zoubir , Brunel Valery , Mulder Paul , Richard Vincent , Bellien Jérémy , Guerrot Dominique
Published: January 2020

Experimental models of cardiovascular diseases largely depend on the genetic background. Subtotal 5/6 nephrectomy (5/6 Nx) is the most frequently used model of chronic kidney disease (CKD) in rodents. However, in mice, cardiovascular consequences of 5/6 Nx are rarely reported in details and comparative results between strains are scarce. The present study detailed and compared the outcomes of 5/6 Nx in the 2 main strains of mice used in cardiovascular and kidney research, 129/Sv and C57BL/6JRj. Twelve weeks after 5/6 Nx, CKD was demonstrated by a significant increase in plasma creatinine in both 129/Sv and C57BL/6JRj male mice. Polyuria and kidney histological lesions were more pronounced in 129/Sv than in C57BL/6JRj mice. Increase in albuminuria was significant in 129/Sv but not in C57BL/6JRj mice. Both strains exhibited an increase in systolic blood pressure after 8 weeks associated with decreases in cardiac systolic and diastolic function. Heart weight increased significantly only in 129/Sv mice. Endothelium-dependent mesenteric artery relaxation to acetylcholine was altered after 5/6 Nx in C57BL/6JRj mice. Marked reduction of endothelium-dependent vasodilation to increased intraluminal flow was demonstrated in both strains after 5/6 Nx. Cardiovascular and kidney consequences of 5/6 Nx were more pronounced in 129/Sv than in C57BL/6JRj mice.
Phosphatidylserine recognition and Rac1 activation are required for Müller glia proliferation, gliosis and phagocytosis after retinal injury
Authors: Nomura-Komoike Kaori , Saitoh Fuminori , Fujieda Hiroki
Published: January 2020

Müller glia, the principal glial cell type in the retina, have the potential to reenter the cell cycle after retinal injury. In mammals, proliferation of Müller glia is followed by gliosis, but not regeneration of neurons. Retinal injury is also accompanied by phagocytic removal of degenerated cells. We here investigated the possibility that proliferation and gliosis of Müller glia and phagocytosis of degenerated cells may be regulated by the same molecular pathways. After N-methyl-N–nitrosourea-induced retinal injury, degenerated photoreceptors were eliminated prior to the infiltration of microglia/macrophages into the outer nuclear layer, almost in parallel with cell cycle reentry of Müller glia. Inhibition of microglia/macrophage activation with minocycline did not affect the photoreceptor clearance. Accumulation of lysosomes and rhodopsin-positive photoreceptor debris within the cytoplasm of Müller glia indicated that Müller glia phagocytosed most photoreceptor debris. Pharmacological inhibition of phosphatidylserine and Rac1, key regulators of the phagocytic pathway, prevented cell cycle reentry, migration, upregulation of glial fibrillary acidic protein, and phagocytic activity of Müller glia. These data provide evidence that phosphatidylserine and Rac1 may contribute to the crosstalk between different signaling pathways activated in Müller glia after injury.
Heat transfer enhancement using CO2 in a natural circulation loop
Authors: Thippeswamy L. R. , Kumar Yadav Ajay
Published: January 2020

The natural circulation loop (NCL) is a highly reliable and noise-free heat transfer device due to the absence of moving components. Working fluid used in the natural circulation loop plays an important role in enhancing the heat transfer capability of the loop. This experimental study investigates the subcritical and supercritical heat transfer performance of a natural circulation loop (NCL) with CO2 as the working fluid. Operating pressures and temperatures are varied in such a way that the loop fluid should remain in the specified state (subcooled liquid, two-phase, superheated vapor, supercritical). Water and methanol are used as external fluids in cold and hot heat exchangers for temperatures above zero and below zero (in °C) respectively, depending on operating temperature. For loop fluids, the performance of CO2 is compared with water for above zero and with brine solution for the subzero case. Further, the impact of loop operating pressure (35–90 bar) on the performance of the system is also studied. For hot heat exchanger inlet temperature (5 to 70 °C) and cold heat exchanger inlet temperature (−18 to 32 °C), it was observed that the maximum heat transfer rates in the case of subcritical vapor, subcritical liquid, two-phase and supercritical CO2 based systems are 400%, 500%, 900%, and 800% higher than the water/brine-based system respectively.
Identification of synergistic drug combinations using breast cancer patient-derived xenografts
Authors: Turner Tia H. , Alzubi Mohammad A. , Harrell J. Chuck
Published: January 2020

Compared with other breast cancer subtypes, triple-negative breast cancer (TNBC) is associated with relatively poor outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative, targeted treatment options, despite decades of major research efforts. Our studies sought to identify promising targeted therapeutic candidates for TNBC through in vitro screening of 1,363 drugs in patient-derived xenograft (PDX) models. Using this approach, we generated a dataset that can be used to assess and compare responses of various breast cancer PDXs to many different drugs. Through a series of further drug screening assays and two-drug combination testing, we identified that the combination of afatinib (epidermal growth factor receptor (EGFR) inhibitor) and YM155 (inhibitor of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5; survivin) expression) is synergistically cytotoxic across multiple models of basal-like TNBC and reduces PDX mammary tumor growth in vivo. We found that YM155 reduces EGFR expression in TNBC cells, shedding light on its potential mechanism of synergism with afatinib. Both EGFR and BIRC5 are highly expressed in basal-like PDXs, cell lines, and patients, and high expression of both genes reduces metastasis-free survival, suggesting that co-targeting of these proteins holds promise for potential clinical success in TNBC.
Co-existence of PrPD types 1 and 2 in sporadic Creutzfeldt-Jakob disease of the VV subgroup: phenotypic and prion protein characteristics
Authors: Cali Ignazio , Puoti Gianfranco , Smucny Jason , Curtiss Paul Michael , Cracco Laura , Kitamoto Tetsuyuki , Occhipinti Rossana , Cohen Mark Lloyd , Appleby Brian Stephen , Gambetti Pierluigi
Published: January 2020

We report a detailed study of a cohort of sporadic Creutzfeldt-Jakob disease (sCJD) VV1–2 type-mixed cases (valine homozygosity at codon 129 of the prion protein, PrP, gene harboring disease-related PrP, PrPD, types 1 and 2). Overall, sCJDVV1–2 subjects showed mixed clinical and histopathological features, which often correlated with the relative amounts of the corresponding PrPD type. However, type-specific phenotypic characteristics were only detected when the amount of the corresponding PrPD type exceeded 20–25%. Overall, original features of types 1 (T1) and 2 (T2) in sCJDVV1 and -VV2, including rostrocaudal relative distribution and conformational indicators, were maintained in sCJDVV1–2 except for one of the two components of T1 identified by electrophoretic mobility as T121. The T121 conformational characteristics shifted in the presence of T2, inferring a conformational effect of PrPD T2 on T121. The prevalence of sCJDVV1–2 was 23% or 57% of all sCJDVV cases, depending on whether standard or highly sensitive type-detecting procedures were adopted. This study, together with previous data from sCJDMM1–2 (methionine homozygosity at PrP gene codon 129) establishes the type-mixed sCJD variants as an important component of sCJD, which cannot be identified with current non-tissue based diagnostic tests of prion disease.
KANSL2 and MBNL3 are regulators of pancreatic ductal adenocarcinoma invasion
Authors: Oladimeji Peter O. , Bakke Jesse , Wright William C. , Chen Taosheng
Published: January 2020

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer. One major reason for this is that PDAC quickly metastasizes to other organs, thereby making its treatment difficult. The molecular machinery driving PDAC metastasis is still poorly understood. In this study, we applied an unbiased approach using CRISPR screening to identify genes that strongly regulate invasion (based on an in vitro assessment of their metastatic potential) in PANC-1, a PDAC cell line. Through CRISPR screening, we identified MBNL3 and KANSL2 as strong regulators of invasion in PANC-1 cells. We further validated MBNL3 and KANSL2 as regulators of PANC-1 cell invasion by using the doxycycline-inducible shRNA system. We also showed that MBNL3 and KANSL2 do not affect cell proliferation. Through our efforts, we have established a process to identify genes that regulate cell invasion and can be further investigated as potential targets for therapeutic intervention.
Evaluation of the antiviral activity of orlistat (tetrahydrolipstatin) against dengue virus, Japanese encephalitis virus, Zika virus and chikungunya virus
Authors: Hitakarun Atitaya , Khongwichit Sarawut , Wikan Nitwara , Roytrakul Sittiruk , Yoksan Sutee , Rajakam Supoth , Davidson Andrew D. , Smith Duncan R.
Published: January 2020

Many mosquito transmitted viruses of the genera Alphavirus and Flavivirus are human pathogens of significant concern, and there is currently no specific antiviral for any member of these two genera. This study sought to investigate the broad utility of orlistat (tetrahydrolipstatin) in reducing virus infection for several mosquito borne viruses including flaviviruses (dengue virus (DENV; nine isolates analyzed), Japanese encephalitis virus (JEV; one isolate analyzed) and Zika virus (ZIKV; 2 isolates analyzed)) as well as an alphavirus (chikungunya virus; CHIKV; 2 isolates analyzed). Three different treatment regimens were evaluated, namely pre-treatment (only), post-treatment (only) and pre- and post-treatment, and three factors were evaluated, namely level of infection, virus titer and genome copy number. Results showed that all three treatment modalities were able to significantly reduce virus titer for all viruses investigated, with the exception of three isolates of DENV in the pre-treatment only regimen. Pre- and post-treatment was more effective in reducing the level of infection and genome copy number of all viruses investigated than either pre-treatment or post-treatment alone. Collectively, these results suggest orlistat has potential as a broad-spectrum agent against multiple mosquito transmitted viruses.
Whole-body vibration modulates leg muscle reflex and blood perfusion among people with chronic stroke: a randomized controlled crossover trial
Authors: Huang Meizhen , Miller Tiev , Ying Michael , Pang Marco Y. C.
Published: January 2020

This study aimed to investigate the acute effect of whole-body vibration (WBV) on the reflex and non-reflex components of spastic hypertonia and intramuscular blood perfusion among individuals with chronic stroke. Thirty-six people with chronic stroke (age: 61.4 ± 6.9 years) participated in this randomized controlled cross-over study. Each participant underwent two testing conditions: static standing for 5 minutes with WBV (30 Hz, 1.5 mm) or no-vibration. We assessed the soleus H-reflex, shear modulus (ultrasound elastography) and vascular index (color power Doppler ultrasound) of the medial gastrocnemius (MG) muscle on either paretic or non-paretic side at baseline and every 1-min post-intervention up to 5 minutes. The results revealed a significant inhibition of the H/M ratio bilaterally for the WBV condition (absolute change on paretic side: 0.61 ± 0.35, p = 0.001; non-paretic side: 0.34 ± 0.23, p = 0.001), but not the control condition. The inhibition of H-reflex was sustained up to 4 minutes and 3 minutes on the paretic and non-paretic side, respectively. The vascular index of MG muscle was significantly increased only for the WBV condition [paretic: from 0.55 ± 0.07 to 1.08 ± 0.18 (p = 0.001); non-paretic: from 0.82 ± 0.09 to 1.01 ± 0.13 (p < 0.001)], which lasted for 3 minutes and 5 minutes, respectively. No significant change of the shear modulus in the MG muscle was observed, regardless of the testing condition. Based on our results, WBV had an acute effect on modulating spastic hypertonia dominated by hyperreflexia in people with chronic stroke and facilitating greater intramuscular blood perfusion. No acute effect on passive muscle stiffness was observed.
Estimation of energy consumed by middle-aged recreational marathoners during a marathon using accelerometry-based devices
Authors: Hernando Carlos , Hernando Carla , Martinez-Navarro Ignacio , Collado-Boira Eladio , Panizo Nayara , Hernando Barbara
Published: January 2020

As long-distance races have substantially increased in popularity over the last few years, the improvement of training programs has become a matter of concern to runners, coaches and health professionals. Triaxial accelerometers have been proposed as a one of the most accurate tools to evaluate physical activity during free-living conditions. In this study, eighty-eight recreational marathon runners, aged 30–45 years, completed a marathon wearing a GENEActiv accelerometer on their non-dominant wrist. Energy consumed by each runner during the marathon was estimated based on both running speed and accelerometer output data, by applying the previously established GENEActiv cut-points for discriminating the six relative-intensity activity levels. Since accelerometry allowed to perform an individualized estimation of energy consumption, higher interpersonal differences in the number of calories consumed by a runner were observed after applying the accelerometry-based approach as compared to the speed-based method. Therefore, pacing analyses should include information of effort intensity distribution in order to adjust race pacing appropriately to achieve the marathon goal time. Several biomechanical and physiological parameters (maximum oxygen uptake, energy cost of running and running economy) were also inferred from accelerometer output data, which is of great value for coaches and doctors.
Surviving the Cretaceous-Paleogene mass extinction event: A terrestrial stem turtle in the Cenozoic of Laurasia
Authors: Pérez-García Adán
Published: January 2020

Findings of terrestrial stem turtles are not uncommon at Mesozoic continental sites in Laurasia, especially during the Upper Cretaceous. Thus, the record of several lineages is known in uppermost Cretaceous ecosystems in North America (Helochelydridae), Europe (Helochelydridae andKallokibotion) and Asia (Sichuanchelyidae). No terrestrial stem turtle had been described in Laurasia after the Cretaceous-Paleogene mass extinction event. Thus, the only representatives described in the Cenozoic record worldwide corresponded to forms from southern Gondwana, where some of them survived until the Holocene. A bizarre terrestrial stem turtle from the upper Thanetian (upper Paleocene) of Europe is described here:Laurasichersis relictagen. et sp. nov. Despite its discovery in France, in Mont de Berru (Marne), this Laurasian taxon is not recognized as a member of a European clade that survived the Cretaceous-Paleogene extinction event. It belongs to Sichuanchelyidae, a hitherto exclusively Asian Mesozoic group, known from the Middle Jurassic. Finds at the Belgian site of Hainin (Hainaut) show that this dispersion from Asia and the occupation of some niches previously dominated by European Mesozoic terrestrial stem forms had already taken place a few million years after the mass extinction event, at the end of the lower Paleocene.
Publisher Correction: Spatial distribution of freshwater crustaceans in Antarctic and Subantarctic lakes
Authors: Díaz Angie , Maturana Claudia S. , Boyero Luz , De Los Ríos Escalante Patricio , Tonin Alan M. , Correa-Araneda Francisco
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Feeding preference of Altica deserticola for leaves of Glycyrrhiza glabra and G. uralensis and its mechanism
Authors: Chang Honglei , Chen Pengyou , Ma Miao
Published: January 2020

Altica deserticola (Coleoptera: Chrysomelidae) is a monophagous insect that feeds on, and is thus a harmful pest of, liquorice. Both adults and larvae feed on leaves, causing serious damage to leaf blades. It will even lead to the extinction of liquorice, resulting in significant economic losses. Leaf-disc tests were used to determine the feeding preference of A. deserticola on leaves of Glycyrrhiza uralensis and G. glabra and explore the underlying mechanism of liquorice feeding resistance to A. deserticola by comparing leaf hardness and thickness, cuticle thickness, and nitrogen and tannin content in the two plants. The results showed that larvae and adults have the same feeding preferences, i.e., both preferably fed on G. uralensis, indicating a higher resistance in this species. The hardness, thickness, and the thickness of the stratum corneum of the leaves of G. glabra were significantly greater than those of G. uralensis. Nitrogen content was higher in G. uralensis, while total tannin, tannic acid, and catechin content were higher in G. glabra. The thick cuticle and hard texture of G. glabra leaves may be an important physical trait for effectively resisting A. deserticola feeding, while high tannin and low nitrogen content may also be important.
Feasibility and clinical applications of multiple breath wash-out (MBW) testing using sulphur hexafluoride in adults with bronchial asthma
Authors: Trinkmann Frederik , Lenz Steffi A. , Schäfer Julia , Gawlitza Joshua , Schroeter Michele , Gradinger Tobias , Akin Ibrahim , Borggrefe Martin , Ganslandt Thomas , Saur Joachim
Published: January 2020

Ventilation heterogeneity is frequent in bronchial asthma and can be assessed using multiple breath wash-out testing (MBW). Most data is available in paediatric patients and using nitrogen as a tracer gas. We aimed to evaluate sulphur hexafluoride (SF6) MBW in adult asthmatics. Spirometry, whole-body plethysmography, impulse oscillometry and SF6-MBW were prospectively performed. MBW parameters reflecting global (lung clearance index, LCI), acinar (Sacin) and conductive (Scond) ventilation heterogeneity were derived from three consecutive wash-outs. LCI was calculated for the traditional 2.5% and an earlier 5% stopping point that has the potential to reduce wash-out times. 91 asthmatics (66%) and 47 non-asthmatic controls (34%) were included in final analysis. LCI2.5 and LCI5 were higher in asthmatics (p < 0.001). Likewise, Sacin and Scond were elevated (p < 0.001 and p < 0.01). Coefficient of variation was 3.4% for LCI2.5 and 3.5% for LCI5 in asthmatics. Forty-one asthmatic patients had normal spirometry. ROC analysis revealed an AUC of 0.906 for the differentiation from non-asthmatic controls exceeding diagnostic performance of individual and conventional parameters (AUC = 0.819, p < 0.05). SF6-MBW is feasible and reproducible in adult asthmatics. Ventilation heterogeneity is increased as compared to non-asthmatic controls persisting in asthmatic patients with normal spirometry. Diagnostic performance is not affected using an earlier LCI stopping point while reducing wash-out duration considerably.
Gastric Cancer Mortality Trends in the Southern Cone: Disentangling age, period and cohort patterns in Argentina and Chile
Authors: Diaz Maria del Pilar , Icaza Gloria , Nuñez Loreto , Pou Sonia A.
Published: January 2020

Although Argentina and Chile are neighboring countries, gastric cancer (GC) is the first cancer death cause in the Chilean male population, while it is ranked in fifth place for Argentinean males. This study is the first to identify the differential time-patterns associated with the age-period-cohort effects for the last few decades (1990–2015) in these Southern Cone countries. Trends of age-standardized truncated mortality rates (ASMR) for GC were analyzed using log-linear Poisson age-period-cohort models, including cubic splines for each component. The ASMR trends for GC decreased in both sexes but more considerably in Chile and more favorably for males (annual percentage changes 2002–2015 = −3.5, 95%CI: −3.9 to −3.1). Moreover, GC age-specific mortality rates were noticeably higher in Chile. A favorable decreasing mortality risk throughout the periods (from 2000) and by cohort was observed for both countries; however, the risk reduction has stabilized in younger female cohorts since 1950-cohort. In conclusion, overall favorable decreasing trends for GC mortality were found; however, when age-period-cohort effects were disentangled, Chile and younger female cohorts showed a more unfavorable scenario. Obesity, lifestyles, and environmental conditions (like altitude) may explain country differences. This analytical approach may be a valuable tool to be replicated in other countries with no population-based cancer registries and acceptable mortality data quality.
Bidirectional relation between depression and sudden sensorineural hearing loss: Two longitudinal follow-up studies using a national sample cohort
Authors: Kim So Young , Min Chanyang , Lee Chang Ho , Park Bumjung , Choi Hyo Geun
Published: January 2020

A few studies have explored the association between depression and sudden sensorineural hearing loss (SSNHL). This study was aimed to investigate the reciprocal relations between SSNHL and depression using a nationwide cohort of the Korean population. Subjects aged > 20 years from the Korean National Health Insurance Service-National Sample Cohort were enrolled from 2002 to 2013. In study I, a total of 60,178 depressed patients were matched 1:4 with 242,872 control I subjects. In study II, a total of 4,328 SSNHL patients were 1:4 matched with 17,312 control II subjects. They were matched for age, sex, income, and region of residence. The Charlson comorbidity index (CCI) was adjusted. Subgroup analysis was performed according to age and sex. The crude and adjusted CCI hazard ratios (HRs) of SSNHL in depressed patients (study I) and depression in SSNHL patients (study II) were analyzed using the stratified Cox proportional-hazard model. In study I, the depression group exhibited an elevated adjusted HR of SSNHL 1.16 times that of the control group (confidence interval [95% CI] = 1.02–1.31, P < 0.023). The middle-aged women subgroup demonstrated an increased risk of SSNHL within the depression group. In study II, the SSNHL group showed a higher adjusted HR of depression 1.29 times that of control II group (95% CI = 1.06–1.57, P = 0.010). The middle-aged women subgroup showed an elevated risk of depression in the SSNHL group. The risk of SSNHL was elevated in the depressed patients and the risk of depression was increased in the SSNHL patients.
Author Correction: HelixComplex snail mucus exhibits pro-survival, proliferative and pro-migration effects on mammalian fibroblasts
Authors: Trapella Claudio , Rizzo Roberta , Gallo Stefania , Alogna Andrea , Bortolotti Daria , Casciano Fabio , Zauli Giorgio , Secchiero Paola , Voltan Rebecca
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Iron induces insulin resistance in cardiomyocytes via regulation of oxidative stress
Authors: Sung Hye Kyoung , Song Erfei , Jahng James Won Suk , Pantopoulos Kostas , Sweeney Gary
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: A global mass budget for positively buoyant macroplastic debris in the ocean
Authors: Lebreton Laurent , Egger Matthias , Slat Boyan
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Collective behaviour in 480-million-year-old trilobite arthropods from Morocco
Authors: Vannier Jean , Vidal Muriel , Marchant Robin , El Hariri Khadija , Kouraiss Khaoula , Pittet Bernard , El Albani Abderrazak , Mazurier Arnaud , Martin Emmanuel
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.