bluuebunny/crossref_metadata_2025 huggingface dataset:
7 Tesla MRI of the ex vivo human brain at 100 micron resolution
Authors: Edlow Brian L. , Mareyam Azma , Horn Andreas , Polimeni Jonathan R. , Witzel Thomas , Tisdall M. Dylan , Augustinack Jean C. , Stockmann Jason P. , Diamond Bram R. , Stevens Allison , Tirrell Lee S. , Folkerth Rebecca D. , Wald Lawrence L. , Fischl Bruce , van der Kouwe Andre
Published: October 2019

We present an ultra-high resolution MRI dataset of an ex vivo human brain specimen. The brain specimen was donated by a 58-year-old woman who had no history of neurological disease and died of non-neurological causes. After fixation in 10% formalin, the specimen was imaged on a 7 Tesla MRI scanner at 100 µm isotropic resolution using a custom-built 31-channel receive array coil. Single-echo multi-flip Fast Low-Angle SHot (FLASH) data were acquired over 100 hours of scan time (25 hours per flip angle), allowing derivation of synthesized FLASH volumes. This dataset provides an unprecedented view of the three-dimensional neuroanatomy of the human brain. To optimize the utility of this resource, we warped the dataset into standard stereotactic space. We now distribute the dataset in both native space and stereotactic space to the academic community via multiple platforms. We envision that this dataset will have a broad range of investigational, educational, and clinical applications that will advance understanding of human brain anatomy in health and disease.
A high-throughput drug combination screen of targeted small molecule inhibitors in cancer cell lines
Authors: Flobak Åsmund , Niederdorfer Barbara , Nakstad Vu To , Thommesen Liv , Klinkenberg Geir , Lægreid Astrid
Published: October 2019

While there is a high interest in drug combinations in cancer therapy, openly accessible datasets for drug combination responses are sparse. Here we present a dataset comprising 171 pairwise combinations of 19 individual drugs targeting signal transduction mechanisms across eight cancer cell lines, where the effect of each drug and drug combination is reported as cell viability assessed by metabolic activity. Drugs are chosen by their capacity to specifically interfere with well-known signal transduction mechanisms. Signalling processes targeted by the drugs include PI3K/AKT, NFkB, JAK/STAT, CTNNB1/TCF, and MAPK pathways. Drug combinations are classified as synergistic based on the Bliss independence synergy metrics. The data identifies combinations that synergistically reduce cancer cell viability and that can be of interest for further pre-clinical investigations.
Transcriptomic profile of cystic fibrosis airway epithelial cells undergoing repair
Authors: Zoso Alice , Sofoluwe Aderonke , Bacchetta Marc , Chanson Marc
Published: October 2019

Pathological remodeling of the airway epithelium is commonly observed in Cystic Fibrosis (CF). The different cell types that constitute the airway epithelium are regenerated upon injury to restore integrity and maintenance of the epithelium barrier function. The molecular signature of tissue repair in CF airway epithelial cells has, however, not well been investigated in primary cultures. We therefore collected RNA-seq data from well-differentiated primary cultures of bronchial human airway epithelial cells (HAECs) of CF (F508del/F508del) and non-CF (NCF) origins before and after mechanical wounding, exposed or not to flagellin. We identified the expression changes with time of repair of genes, the products of which are markers of the different cell types that constitute the airway epithelium (basal, suprabasal, intermediate, secretory, goblet and ciliated cells as well as ionocytes). Researchers in the CF field may benefit from this transcriptomic profile, which covers the initial steps of wound repair and revealed differences in this process between CF and NCF cultures.
Noise-free simulation of an FT-IR imaging hyperspectral dataset of pancreatic biopsy core bound by experiment
Authors: Wrobel Tomasz P. , Koziol Paulina , Raczkowska Magda K. , Liberda Danuta , Paluszkiewicz Czeslawa , Kwiatek Wojciech M.
Published: October 2019

A noise-free hyperspectral FT-IR imaging dataset of a pancreatic tissue core was simulated based on experimental data that allows to test the performance of various data analysis and processing algorithms. A set of experimental noise levels was also added and used for denoising approaches comparison, which due to the noise-free reference signal enables to truly observe signal distortion caused by different approaches.
Structural and thermodynamic basis for the recognition of the substrate-binding cleft on hen egg lysozyme by a single-domain antibody
Authors: Akiba Hiroki , Tamura Hiroko , Kiyoshi Masato , Yanaka Saeko , Sugase Kenji , Caaveiro Jose M. M. , Tsumoto Kouhei
Published: October 2019

Single-domain antibodies (VHHs or nanobodies), developed from heavy chain-only antibodies of camelids, are gaining attention as next-generation therapeutic agents. Despite their small size, the high affinity and specificity displayed by VHHs for antigen molecules rival those of IgGs. How such small antibodies achieve that level of performance? Structural studies have revealed that VHHs tend to recognize concave surfaces of their antigens with high shape-complementarity. However, the energetic contribution of individual residues located at the binding interface has not been addressed in detail, obscuring the actual mechanism by which VHHs target the concave surfaces of proteins. Herein, we show that a VHH specific for hen egg lysozyme, D3-L11, not only displayed the characteristic binding of VHHs to a concave region of the surface of the antigen, but also exhibited a distribution of energetic hot-spots like those of IgGs and conventional protein-protein complexes. The highly preorganized and energetically compact interface of D3-L11 recognizes the concave epitope with high shape complementarity by the classical lock-and-key mechanism. Our results shed light on the fundamental basis by which a particular VHH accommodate to the concave surface of an antigens with high affinity in a specific manner, enriching the mechanistic landscape of VHHs.
A large intragenic deletion in the CLCN1 gene causes Hereditary Myotonia in pigs
Authors: Araújo C. E. T. , Oliveira C. M. C. , Barbosa J. D. , Oliveira-Filho J. P. , Resende L. A. L. , Badial P. R. , Araujo-Junior J. P. , McCue M. E. , Borges A. S.
Published: October 2019

Mutations in the CLCN1 gene are the primary cause of non-dystrophic Hereditary Myotonia in several animal species. However, there are no reports of Hereditary Myotonia in pigs to date. Therefore, the objective of the present study was to characterize the clinical and molecular findings of Hereditary Myotonia in an inbred pedigree. The clinical, electromyographic, histopathological, and molecular findings were evaluated. Clinically affected pigs presented non-dystrophic recessive Hereditary Myotonia. Nucleotide sequence analysis of the entire coding region of the CLCN1 gene revealed the absence of the exons 15 and 16 in myotonic animals. Analysis of the genomic region flanking the deletion unveiled a large intragenic deletion of 4,165 nucleotides. Interestingly, non-related, non-myotonic pigs expressed transcriptional levels of an alternate transcript (i.e., X2) that was identical to the deleted X1 transcript of myotonic pigs. All myotonic pigs and their progenitors were homozygous recessive and heterozygous, respectively, for the 4,165-nucleotide deletion. This is the first study reporting Hereditary Myotonia in pigs and characterizing its clinical and molecular findings. Moreover, to the best of our knowledge, Hereditary Myotonia has never been associated with a genomic deletion in the CLCN1 gene in any other species.
Response of Coffee Farms to Hurricane Maria: Resistance and Resilience from an Extreme Climatic Event
Authors: Perfecto Ivette , Hajian-Forooshani Zachary , Iverson Aaron , Irizarry Amarilys D. , Lugo-Perez Javier , Medina Nicholas , Vaidya Chatura , White Alexa , Vandermeer John
Published: October 2019

Resistance and resilience have become important concepts in the evaluation of disturbance events, providing a framework that is useful in light of the expected increase in frequency and occurrences of hurricanes as a consequence of climate change. Hurricane Maria landed on Puerto Rico as a category 4 storm in September of 2017. Among the affected elements were agricultural systems, including coffee agroecosystems. Historically, coffee has been a major backbone of the island’s agricultural sector. Grown with a range of management styles, the coffee agroecosystem provides an excellent model system to study the resistance/resilience of agroecosystems faced with hurricane disturbance. Sampling 28 farms and comparing pre-hurricane data (2013) with post hurricane data we find that management style had only a small effect on either resistance or resilience, likely due to the especially strong nature of the storm. Rather, the socio-political context of individual farms seems to be a more useful predictor of resilience.
Large and tunable magnetocaloric effect in gadolinium-organic framework: tuning by solvent exchange
Authors: Zeleňák Vladimír , Almáši Miroslav , Zeleňáková Adriána , Hrubovčák Pavol , Tarasenko Róbert , Bourelly Sandrine , Llewellyn Philip
Published: October 2019

Magnetic properties of three variants of MOF-76(Gd), {[Gd(BTC)(H2O)]·G}n (BTC = benzene-1,3,5-tricarboxylate, G = guest molecules) were investigated by static susceptibility, isothermal magnetization and specific heat capacity measurements. In the study we used as synthesized MOF-76(Gd)-DMF (1) (G = DMF = dimethylformamide), containing DMF molecules in the cavity system, compound MOF-76(Gd) (2), activated complex without solvents in the cavities and water exchanged sample MOF-76(Gd)-H2O (3). A pronounced change in the magnetic entropy was found near the critical temperature for all three compounds. It was shown, that magnetic entropy change depends on the solvatation of the MOF. The highest value entropy change, ΔSMpk(T) was observed for compound 2 (ΔSMpk(T) = 42 J kg−1 K−1 at 1.8 K for ΔH = 5 T). The ΔSMpk(T) for the compounds 1, 2 and 3 reached 81.8, 88.4 and 100% of the theoretical values, respectively. This suggests that in compound 3 Gd3+···Gd3+ antiferromagnetic interactions are decoupled gradually, and higher fields promote a larger decoupling between the individual spin centers. The observed entropy changes of compounds were comparable with other magnetic refrigerants proposed for low-temperature applications. To study the magnetothermal effect of 2 (the sample with largest −ΔSMpk), the temperature-dependent heat capacities (C) at different fields were measured. The value of magnetic entropy S obtained from heat capacities (39.5 J kg−1 K−1 at 1.8 K for an applied magnetic field change of 5 T) was in good agreement with that derived from the magnetization data (42 J kg−1 K−1 at 1.8 K).
Differential Treatments Based on Drug-induced Gene Expression Signatures and Longitudinal Systemic Lupus Erythematosus Stratification
Authors: Toro-Domínguez Daniel , Lopez-Domínguez Raúl , García Moreno Adrián , Villatoro-García Juan A. , Martorell-Marugán Jordi , Goldman Daniel , Petri Michelle , Wojdyla Daniel , Pons-Estel Bernardo A. , Isenberg David , Morales-Montes de Oca Gabriela , Trejo-Zambrano María Isabel , García González Benjamín , Rosetti Florencia , Gómez-Martín Diana , Romero-Díaz Juanita , Carmona-Sáez Pedro , Alarcón-Riquelme Marta E.
Published: October 2019

Systemic lupus erythematosus (SLE) is a heterogeneous disease with unpredictable patterns of activity. Patients with similar activity levels may have different prognosis and molecular abnormalities. In this study, we aimed to measure the main differences in drug-induced gene expression signatures across SLE patients and to evaluate the potential for clinical data to build a machine learning classifier able to predict the SLE subset for individual patients. SLE transcriptomic data from two cohorts were compared with drug-induced gene signatures from the CLUE database to compute a connectivity score that reflects the capability of a drug to revert the patient signatures. Patient stratification based on drug connectivity scores revealed robust clusters of SLE patients identical to the clusters previously obtained through longitudinal gene expression data, implying that differential treatment depends on the cluster to which patients belongs. The best drug candidates found, mTOR inhibitors or those reducing oxidative stress, showed stronger cluster specificity. We report that drug patterns for reverting disease gene expression follow the cell-specificity of the disease clusters. We used 2 cohorts to train and test a logistic regression model that we employed to classify patients from 3 independent cohorts into the SLE subsets and provide a clinically useful model to predict subset assignment and drug efficacy.
A Low Cost and Portable Microwave Imaging System for Breast Tumor Detection Using UWB Directional Antenna array
Authors: Islam M. T. , Mahmud M. Z. , Islam M. Tarikul , Kibria S. , Samsuzzaman M.
Published: October 2019

Globally, breast cancer is a major reason for female mortality. Due to the limitations of current clinical imaging, the researchers are encouraged to explore alternative and complementary tools to available techniques to detect the breast tumor in an earlier stage. This article outlines a new, portable, and low-cost microwave imaging (MWI) system using an iterative enhancing technique for breast imaging. A compact side slotted tapered slot antenna is designed for microwave imaging. The radiating fins of tapered slot antenna are modified by etching nine rectangular side slots. The irregular slots on the radiating fins enhance the electrical length as well as produce strong directive radiation due to the suppression of induced surface currents that radiate vertically at the outer edges of the radiating arms with end-fire direction. It has remarkable effects on efficiency and gain. With the addition of slots, the side-lobe levels are reduced, the gain of the main-lobe is increased and corrects the squint effects simultaneously, thus improving the characteristics of the radiation. For experimental validation, a heterogeneous breast phantom was developed that contains dielectric properties identical to real breast tissues with the inclusion of tumors. An alternative PC controlled and microcontroller-based mechanical MWI system is designed and developed to collect the antenna scattering signal. The radiated backscattered signals from the targeted area of the human body are analyzed to reveal the changes in dielectric properties in tissues. The dielectric constants of tumorous cells are higher than that of normal tissues due to their higher water content. The remarkable deviation of the scattered field is processed by using newly proposed Iteratively Corrected Delay and Sum (IC-DAS) algorithm and the reconstruction of the image of the phantom interior is done. The developed UWB (Ultra-Wideband) antenna based MWI has been able to perform the detection of tumorous cells in breast phantom that can pave the way to saving lives.
Ag-AgCl Nanoparticles Fixation on Electrospun PVA Fibres: Technological Concept and Progress
Authors: Vilamová Zuzana , Konvičková Zuzana , Mikeš Petr , Holišová Veronika , Mančík Pavel , Dobročka Edmund , Kratošová Gabriela , Seidlerová Jana
Published: October 2019

Polymer-metal based material with unique 3D structure is an attractive substrate for the development of biomedical applications. A novel preparation of the composite from polymer fibres and silver nanoparticles has been designed through: (1) preparation of silver nanoparticles by phytosynthesis and (2) incorporation of these nanoparticles in a fibrous membrane prepared by electrospinning. The nanoparticle biosynthesis was performed in a pure environmental-friendly, easy, static, bottom-up in vitro regime using Tilia sp. leachate. TEM and XRD depict the formation, stabilisation and encapsulation of crystalline silver (14 ± 9 nm) nanoparticles (NPs) in one simple step with low tendency to aggregate. We achieved successful incorporation in the uniform electrospun 221 ± 24 nm poly(vinylalcohol) fibres, and this confirms the possibility of its use in the biomedical field. Both SEM with EDX and TEM analysis determined fibre uniformity with the presence of silver NPs, and ICP-AES confirmed the relatively similar metal concentration throughout the triplicate measurement of fibre structures on the 2 × 2 cm area in the following manner: 0.303 ± 0.018 wt. %, 0.282 ± 0.017 wt. %, and 0.281 ± 0.017 wt. %. Our hypothesis is based on previously verified preparation of active silver NPs and the easily prepared PVA electrospun fibres which act as a water soluble matrix. The simple methodology of incorporating biosynthetically prepared NPs in the PVA fibers highlights the effectiveness of this material, with simple release from water-soluble PVA and final activation of the prepared NPs.
Empagliflozin and Dulaglutide are Effective against Obesity-induced Airway Hyperresponsiveness and Fibrosis in A Murine Model
Authors: Park Hye Jung , Han Heejae , Oh Eun-Yi , Kim Sung Ryeol , Park Kyung Hee , Lee Jae-Hyun , Park Jung-Won
Published: October 2019

Patients with asthma with obesity experience severe symptoms, are unresponsive to conventional asthma treatment, and lack proper pharmacotherapy. Empagliflozin and dulaglutide, developed for diabetes, reduce weight, decrease insulin resistance, and exert additive effects. We evaluated the efficacy of empagliflozin, dulaglutide, and their combination on obesity-induced airway hyperresponsiveness (AHR) and lung fibrosis using a murine model. We assigned C57BL/6J mice to five groups: control, high-fat diet (HFD), and HFD with empagliflozin, dulaglutide, or both. Mice received a 12-week HFD, empagliflozin (5 days/week, oral gavage), and dulaglutide (once weekly, intraperitoneally). Both drugs significantly attenuated HFD-induced weight increase, abnormal glucose metabolism, and abnormal serum levels of leptin and insulin, and co-treatment was more effective. Both drugs significantly alleviated HFD-induced AHR, increased macrophages in bronchoalveolar lavage fluid (BALF), and co-treatment was more effective on AHR. HFD-induced lung fibrosis was decreased by both drugs alone and combined. HFD induced interleukin (IL)-17, transforming growth factor (TGF)-β1, and IL-1β mRNA and protein expression, which was significantly reduced by empagliflozin, dulaglutide, and their combination. Tumour necrosis factor (TNF)-α and IL-6 showed similar patterns without significant differences. HFD-enhanced T helper (Th) 1 and Th17 cell differentiation was improved by both drugs. Empagliflozin and dulaglutide could be a promising therapy for obesity-induced asthma and showed additive effects in combination.
Altered temporal sensitivity in obesity is linked to pro-inflammatory state
Authors: Scarpina Federica , Marzullo Paolo , Mai Stefania , Mauro Alessandro , Scacchi Massimo , Costantini Marcello
Published: October 2019

Temporal sensitivity to multisensory stimuli has been shown to be reduced in obesity. We sought to investigate the possible role of the pro-inflammatory state on such alteration, considering the effect of the expression of markers, such as leptin and IL6, which are notably high in obesity. The performance of 15 male individuals affected by obesity and 15 normal-weight males was compared using two audiovisual temporal tasks, namely simultaneity judgment and temporal order judgment. Analyses of serum levels of inflammatory markers of leptin and IL6, and of neurotrophic factors of BDNF and S100SB were quantified. At the behavioral level we confirmed previous evidence showing poorer temporal sensitivity in obesity compared to normal-weight participants. Furthermore, leptin, that is a cytokine overexpressed in obesity, represented the best predictor of behavioral differences between groups in both tasks. The hypothesis we put forward is that the immune system, rather than overall cerebral dysfunction, might contribute to explain the altered temporal sensitivity in obesity. The present finding is discussed within the context of the role of cytokines on the brain mechanisms supporting temporal sensitivity.
Allergic rhinitis is a risk factor of gastro-esophageal reflux disease regardless of the presence of asthma
Authors: Kung Yu-Min , Tsai Pei-Yun , Chang Yu-Han , Wang Yao-Kuang , Hsieh Meng-Shu , Hung Chih-Hsing , Kuo Chao-Hung
Published: October 2019

Gastroesophageal reflux disease (GERD) can cause several upper airway symptoms and alter the physiology of nasopharyngeal mucosa, while upper airway diseases in turn might also exacerbate GERD symptoms. For a long time, asthma was considered a risk factor of GERD in the literature. Asthma and allergic rhinitis (AR) are usually identified as united airway disease according to similar epidemiology and pathophysiology; however, the association between AR and GERD is less elucidated. We aimed to evaluate whether AR would increase the development of GERD. Patients diagnosed as AR were identified from the National Health Insurance Research Database between January 1, 2000 and December 31, 2005 without prior history of gastroesophageal reflux disease. The outcome of interest was new-onset GERD. Cox regression models were applied to calculate the hazard ratio (HR) of GERD. We analyzed the data of 193,810 AR patients aged 18 years or older and being free of AR at baseline. The AR cohort (n = 96,905) had a significantly increased risk of GERD over a non-AR cohort (n = 96905) (adjusted HR (aHR) 1.94; 95% CI = 1.88–1.99, p < 0.001). AR may have stronger correlation with GERD than does asthma, although asthma might increase GERD risk by means of certain pathways shared with AR.
Mechanisms of soft tissue and protein preservation in Tyrannosaurus rex
Authors: Boatman Elizabeth M. , Goodwin Mark B. , Holman Hoi-Ying N. , Fakra Sirine , Zheng Wenxia , Gronsky Ronald , Schweitzer Mary H.
Published: October 2019

The idea that original soft tissue structures and the native structural proteins comprising them can persist across geological time is controversial, in part because rigorous and testable mechanisms that can occur under natural conditions, resulting in such preservation, have not been well defined. Here, we evaluate two non-enzymatic structural protein crosslinking mechanisms, Fenton chemistry and glycation, for their possible contribution to the preservation of blood vessel structures recovered from the cortical bone of a Tyrannosaurus rex (USNM 555000 [formerly, MOR 555]). We demonstrate the endogeneity of the fossil vessel tissues, as well as the presence of type I collagen in the outermost vessel layers, using imaging, diffraction, spectroscopy, and immunohistochemistry. Then, we use data derived from synchrotron FTIR studies of the T. rex vessels to analyse their crosslink character, with comparison against two non-enzymatic Fenton chemistry- and glycation-treated extant chicken samples. We also provide supporting X-ray microprobe analyses of the chemical state of these fossil tissues to support our conclusion that non-enzymatic crosslinking pathways likely contributed to stabilizing, and thus preserving, these T. rex vessels. Finally, we propose that these stabilizing crosslinks could play a crucial role in the preservation of other microvascular tissues in skeletal elements from the Mesozoic.
Relations of non-motor symptoms and dopamine transporter binding in REM sleep behavior disorder
Authors: Dušek Petr , Ibarburu Veronika Lorenzo y Losada , Bezdicek Ondrej , Dall’antonia Irene , Dostálová Simona , Kovalská Petra , Krupička Radim , Nepožitek Jiří , Nikolai Tomáš , Novotný Michal , Peřinová Pavla , Rusz Jan , Serranová Tereza , Tykalová Tereza , Ulmanová Olga , Mecková Zuzana , Ptáčník Václav , Trnka Jiří , Zogala David , Růžička Evžen , Šonka Karel
Published: October 2019

The aim of this study was to evaluate associations of motor and non-motor symptoms with dopamine transporter binding in prodromal stage of synucleinopathies. We examined 74 patients with idiopathic REM sleep behavior disorder (RBD), which is a prodromal synucleinopathy, and 39 controls using Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment, University of Pennsylvania Smell Identification Test (UPSIT), Farnsworth-Munsell 100 hue test, orthostatic test, Scales for Outcomes in PD-Autonomic, Beck depression inventory-II, State-Trait Anxiety Inventory, and video-polysomnography. Electromyographic muscle activity during REM sleep was quantified according to Sleep Innsbruck-Barcelona criteria. In 65 patients, dopamine transporter single-photon emission computed tomography (DAT-SPECT) imaging was performed, putaminal binding ratio was calculated and scans were classified as normal, borderline, or abnormal. Compared to controls, RBD patients had significantly more severe scores in all examined tests. Patients with abnormal DAT-SPECT had higher MDS-UPDRS motor score (p = 0.006) and higher prevalence of orthostatic hypotension (p = 0.008). Putaminal binding ratio was positively associated with UPSIT score (p = 0.03) and negatively associated with tonic (p = 0.003) and phasic (p = 0.01) muscle activity during REM sleep. These associations likely reflect simultaneous advancement of underlying pathology in substantia nigra and susceptible brainstem and olfactory nuclei in prodromal synucleinopathy.
Lipopolysaccharide-induced expansion of histidine decarboxylase-expressing Ly6G+ myeloid cells identified by exploiting histidine decarboxylase BAC-GFP transgenic mice
Authors: Takai Jun , Ohtsu Hiroshi , Sato Atsushi , Uemura Satoshi , Fujimura Tsutomu , Yamamoto Masayuki , Moriguchi Takashi
Published: October 2019

Histamine is a biogenic amine that is chiefly produced in mast cells and basophils and elicits an allergic response upon stimulation. Histidine decarboxylase (HDC) is a unique enzyme that catalyzes the synthesis of histamine. Therefore, the spatiotemporally specificHdcgene expression profile could represent the localization of histamine-producing cells under various pathophysiological conditions. Although the bioactivity of histamine is well defined, the regulatory mechanism ofHdcgene expression and the distribution of histamine-producing cell populations in various disease contexts remains unexplored. To address these issues, we generated a histidine decarboxylase BAC (bacterial artificial chromosome) DNA-directed GFP reporter transgenic mouse employing a 293-kb BAC clone containing the entireHdcgene locus and extended flanking sequences (Hdc-GFP). We found that the GFP expression pattern in theHdc-GFP mice faithfully recapitulated that of conventional histamine-producing cells and that the GFP expression level mirrored the increasedHdcexpression in lipopolysaccharide (LPS)-induced septic lungs. Notably, a CD11b+Ly6G+Ly6Clowmyeloid cell population accumulated in the lung during sepsis, and most of these cells expressed high levels of GFP and indeed contain histamine. This study reveals the accumulation of a histamine-producing myeloid cell population during sepsis, which likely participates in the immune process of sepsis.
The roles of grouper clathrin light chains in regulating the infection of a novel marine DNA virus, Singapore grouper iridovirus
Authors: Wang Liqun , Li Qiang , Ni Songwei , Huang Youhua , Wei Jingguang , Liu Jiaxin , Yu Yepin , Wang Shaowen , Qin Qiwei
Published: October 2019

Clathrins, composed of clathrin heavy chains (CHCs) and clathrin light chains (CLCs), are usually hijacked by viruses for infection. However, the role of CLCs, especially in regulating fish virus infection, remains poorly understood. Here, two isoforms of CLCs were cloned from the red-spotted grouper (Epinephelus akaara) (EaCLCa and EaCLCb). Both EaCLC transcripts were expressed in all examined tissues, and the expression of EaCLCa was much higher than that of EaCLCb. Over-expressing EaCLCa-W119R mutant significantly reduced Singapore grouper iridovirus (SGIV) infectivity. However, no effect of EaCLCb-W122R on SGIV infection was observed. The detailed steps were further studied, mainly including virus attachment, entry and the following transport to early endosomes. EaCLCa-W119R mutant notably inhibited internalization of SGIV particles with no effect on SGIV attachment. Furthermore, EaCLCa-W119R mutant obviously impaired the delivery of SGIV to early endosomes after virus internalization. In addition, the EaCLCa-W119R mutant markedly reduced the colocalization of SGIV and actin. However, EaCLCb is not required for such events during SGIV infection. Taken together, these results demonstrate for the first time that EaCLCa and EaCLCb exerted different impacts on iridovirus infection, providing a better understanding of the mechanisms of SGIV infection and opportunities for the design of new antiviral strategies.
Cigarette smoke extract exacerbates hyperpermeability of cerebral endothelial cells after oxygen glucose deprivation and reoxygenation
Authors: Bernard Ashton , Ku Jacqueline M. , Vlahos Ross , Miller Alyson A.
Published: October 2019

Cigarette smoking is a risk factor for stroke and is linked to stroke severity. Previous studies have shown that cigarette smoke extract (CSE) triggers endothelial dysfunction in vitro by initiating oxidative stress and/or an inflammatory response. In addition, cerebral endothelial dysfunction (particularly at the level of the blood-brain barrier [BBB]) contributes to stroke pathogenesis. Therefore, we hypothesized that cigarette smoking may influence stroke, at least in part, by exacerbating ischaemia-induced BBB disruption. To test this, we examined the effect of CSE on the permeability of cerebral endothelial cells exposed to oxygen glucose deprivation and reoxygenation (OGD + RO). We found that the loss of BBB integrity following ischaemic/reperfusion-like conditions was significantly worsened by CSE. Despite this being associated with increased mRNA expression of Nox catalytic subunits, reactive oxygen species (ROS) levels were however markedly lower. Furthermore, this occurred in association with elevated expression of antioxidant enzymes (SOD1, SOD2, and Gpx-1), suggesting an antioxidant defence response. Lastly, we found that CSE significantly upregulated mRNA expression of cytokines (IL-6 and TGF-β). Collectively, these results show that acute exposure to CSE worsens BBB disruption caused by OGD + RO, however, this is not linked to elevated ROS levels but may involve inflammatory mechanisms.
Robot-assisted Nipple-sparing Mastectomy with Immediate Breast Reconstruction: An Initial Experience
Authors: Park Hyung Seok , Lee Jeea , Lee Dong Won , Song Seung Yong , Lew Dae Hyun , Kim Seung Il , Cho Young Up
Published: October 2019

Seeking smaller and indistinct incisions, physicians have attempted endoscopic breast surgery in breast cancer patients. Unfortunately, there are some limitations in the range of movement and visualization of the operation field. Potentially addressing these limitations, we investigated the outcomes of gas and gasless robot-assisted nipple-sparing mastectomy (RANSM) with immediate breast reconstruction (IBR). Ten patients underwent 12 RANSM with IBR between November 2016 and April 2018. Patients with tumors measuring >5 cm in diameter, tumor invasion of the skin or nipple-areolar complex, proven metastatic lymph nodes, or planned radiotherapy were excluded. Age, breast weight, diagnosis, tumor size, hormone receptor status, and operation time were retrospectively collected. Postoperative outcomes including postoperative complications and final margin status of resected were analyzed. The median total operation time and console time were 351 min (267–480 min) and 51 min (18–143 min), respectively. The learning curve presented as a cumulative sum graph showed that the console time decreased and then stabilized at the eighth case. There was no open conversion or major postoperative complication. One patient had self-resolved partial nipple ischemia, and two patients experienced partial skin ischemia. We deemed that RANSM with IBR is safe and feasible for early breast cancer, benign disease of the breast, andBRCA 1/2mutation carriers. RANSM is an advanced surgical method with a short learning curve.
Uterine SOX17: a key player in human endometrial receptivity and embryo implantation
Authors: Kinnear Sophie , Salamonsen Lois A. , Francois Mathias , Harley Vincent , Evans Jemma
Published: October 2019

The yin and yang of female fertility is a complicated issue; large numbers of women/couples desire fertility and seek assisted reproduction intervention to achieve conception, while others seek to prevent pregnancy. Understanding specific molecules which control endometrial-embryo interactions is essential for both facilitating and preventing pregnancy. SOX17 has recently emerged as an important transcription factor involved in endometrial receptivity and embryo implantation. However, studies to date have examined mouse models of pregnancy which do not necessarily translate to the human. Demonstration of a role for ‘implantation factors’ in a human system is critical to provide a rationale for in depth clinical investigation and targeting of such factors. We demonstrate that SOX17is present within the receptive human endometrium and is up-regulated within human endometrial epithelial cells by combined estrogen & progesterone, the hormonal milieu during the receptive window. SOX17 localizes to the point of adhesive contact between human endometrial epithelial cells and a human ‘embryo mimic’ model (trophectodermal spheroid). Targeting SOX17 in endometrial epithelial cells using CRISPR/Cas9 knockdown or a SOX-F family inhibitor, MCC177, significantly inhibited adhesion of an trophectodermal spheroids to the epithelial cells thereby preventing ‘implantation’. These data confirm the important role of endometrial SOX17 in human endometrial receptivity and embryo implantation.
Association between Atrial Fibrillation, Myocardial Infarction, Heart Failure and Mortality in Patients with Nontuberculous Mycobacterial Infection: a nationwide population-based study
Authors: Park Chan Soon , Choi Eue-Keun , Kim Bongseong , Han Kyung-Do , Lee So-Ryoung , Cha Myung-Jin , Oh Seil
Published: October 2019

NTM infection demonstrates an increasing incidence and prevalence. We studied the impact of NTM in cardiovascular events. Using the Korean nationwide database, we included newly diagnosed 1,730 NTM patients between 2005 and 2008 and followed up for new-onset atrial fibrillation (AF), myocardial infarction (MI), heart failure (HF), ischemic stroke (IS), and death. Covariates-matched non-NTM subjects (1:5, n = 8,650) were selected and analyzed. Also, NTM infection was classified into indolent or progressive NTM for risk stratification. During 4.16 ± 1.15 years of the follow-up period, AF, MI, HF, IS, and death were newly diagnosed in 87, 125, 121, 162, and 468 patients. In multivariate analysis, NTM group showed an increased risk of AF (hazard ratio [HR] 2.307, 95% confidence interval [CI] 1.560–3.412) and all-cause death (HR 1.751, 95% CI 1.412–2.172) compared to non-NTM subjects, whereas no significant difference in MI (HR 0.868, 95% CI 0.461–1.634), HF (HR 1.259, 95% CI 0.896–2.016), and IS (HR 1.429, 95% CI 0.981–2.080). After stratification, 1,730 NTM patients were stratified into 1,375 (79.5%) indolent NTM group and 355 (20.5%) progressive NTM group. Progressive NTM showed an increased risk of AF and mortality than indolent NTM group. Screening for AF and IS prevention would be appropriate in these high-risk patients.
Shape of a recoiling liquid filament
Authors: Contò Francesco Paolo , Marín Juan F. , Antkowiak Arnaud , Castrejón-Pita J. Rafael , Gordillo Leonardo
Published: October 2019

We study the capillary retraction of a Newtonian semi-infinite liquid filament through analytical methods. We derive a long-time asymptotic-state expansion for the filament profile using a one-dimensional free-surface slender cylindrical flow model based on the three-dimensional axisymmetric Navier-Stokes equations. The analysis identifies three distinct length and time scale regions in the retraction domain: a steady filament section, a growing spherical blob, and an intermediate matching zone. We show that liquid filaments naturally develop travelling capillary waves along their surface and a neck behind the blob. We analytically prove that the wavelength of the capillary waves is approximately 3.63 times the filament’s radius at the inviscid limit. Additionally, the waves’ asymptotic wavelength, decay length, and the minimum neck size are analysed in terms of the Ohnesorge number. Finally, our findings are compared with previous results from the literature and numerical simulations in Basilisk obtaining a good agreement. This analysis provides a full picture of the recoiling process going beyond the classic result of the velocity of retraction found by Taylor and Culick.
Morphology and development of the Portuguese man of war, Physalia physalis
Authors: Munro Catriona , Vue Zer , Behringer Richard R. , Dunn Casey W.
Published: October 2019

The Portuguese man of war, Physalia physalis, is one of the most conspicuous, but poorly understood members of the pleuston, a community of organisms that occupy a habitat at the sea-air interface. Physalia physalis is a siphonophore that uses a gas-filled float as a sail to catch the wind. The development, morphology, and colony organization of P. physalis is very different from all other siphonophores. Here, we look at live and fixed larval and juvenile specimens, and use optical projection tomography to build on existing knowledge about the morphology and development of this species. We also propose a framework for homologizing the axes with other siphonophores, and also suggest that the tentacle bearing zooids should be called tentacular palpons. Previous descriptions of P. physalis larvae, especially descriptions of budding order, were often framed with the mature colony in mind. However, we use the simpler organization of larvae and the juvenile specimens to inform our understanding of the morphology, budding order, and colony organization in the mature specimen. Finally, we review what is known about the ecology and lifecycle of P. physalis.
Phase Matching Quantum Key Distribution based on Single-Photon Entanglement
Authors: Li Wei , Wang Le , Zhao Shengmei
Published: October 2019

Two time-reversal quantum key distribution (QKD) schemes are the quantum entanglement based device-independent (DI)-QKD and measurement-device-independent (MDI)-QKD. The recently proposed twin field (TF)-QKD, also known as phase-matching (PM)-QKD, has improved the key rate bound from O(η) to O$$(\sqrt{{\boldsymbol{\eta }}})$$
(

η

)
with η the channel transmittance. In fact, TF-QKD is a kind of MDI-QKD but based on single-photon detection. In this paper, we propose a different PM-QKD based on single-photon entanglement, referred to as single-photon entanglement-based phase-matching (SEPM)-QKD, which can be viewed as a time-reversed version of the TF-QKD. Detection loopholes of the standard Bell test, which often occur in DI-QKD over long transmission distances, are not present in this protocol because the measurement settings and key information are the same quantity which is encoded in the local weak coherent state. We give a security proof of SEPM-QKD and demonstrate in theory that it is secure against all collective attacks and beam-splitting attacks. The simulation results show that the key rate enjoys a bound of O$$(\sqrt{{\boldsymbol{\eta }}})$$
(

η

)
with respect to the transmittance. SEPM-QKD not only helps us understand TF-QKD more deeply, but also hints at a feasible approach to eliminate detection loopholes in DI-QKD for long-distance communications.
Molecular Imaging of Endometriosis Tissues using Desorption Electrospray Ionization Mass Spectrometry
Authors: Feider Clara L. , Woody Spencer , Ledet Suzanne , Zhang Jialing , Sebastian Katherine , Breen Michael T. , Eberlin Livia S.
Published: October 2019

Endometriosis is a pathologic condition affecting approximately 10% of women in their reproductive years. Characterized by abnormal growth of uterine endometrial tissue in other body areas, endometriosis can cause severe abdominal pain and/or infertility. Despite devastating consequences to patients’ quality of life, the causes of endometriosis are not fully understood and validated diagnostic markers for endometriosis have not been identified. Molecular analyses of ectopic and eutopic endometrial tissues could lead to enhanced understanding of the disease. Here, we apply desorption electrospray ionization (DESI) mass spectrometry (MS) imaging to chemically and spatially characterize the molecular profiles of 231 eutopic and ectopic endometrial tissues from 89 endometriosis patients. DESI-MS imaging allowed clear visualization of endometrial glandular and stromal regions within tissue samples. Statistical models built from DESI-MS imaging data allowed classification of endometriosis lesions with overall accuracies of 89.4%, 98.4%, and 98.8% on training, validation, and test sample sets, respectively. Further, molecular markers that are significantly altered in ectopic endometrial tissues when compared to eutopic tissues were identified, including fatty acids and glycerophosphoserines. Our study showcases the value of MS imaging to investigate the molecular composition of endometriosis lesions and pinpoints metabolic markers that may provide new knowledge on disease pathogenesis.
Diversity of PBI-DdeI satellite DNA in snakes correlates with rapid independent evolution and different functional roles
Authors: Thongchum Ratchaphol , Singchat Worapong , Laopichienpong Nararat , Tawichasri Panupong , Kraichak Ekaphan , Prakhongcheep Ornjira , Sillapaprayoon Siwapech , Muangmai Narongrit , Baicharoen Sudarath , Suntrarachun Sunutcha , Chanhome Lawan , Peyachoknagul Surin , Srikulnath Kornsorn
Published: October 2019

To better understand PBI-DdeI satellite DNA located in the centromeric region of python, molecular evolution analysis was conducted on 40 snake species. A ladder-like pattern of DNA bands with repetition of the 194–210 bp monomer was observed in 15 species using PCR. Molecular cloning was performed to obtain 97 AT-rich monomer sequences. Phylogenetic and network analyses showed three PBI-DdeI subfamilies with sequences grouped in species-specific clusters, suggesting rapid evolution. Slow evolution was found in eight species with shared PBI-DdeI sequences, suggesting recent species diversification, allowing PBI-DdeI no time to diverge, with limited homogenization and fixation processes. Quantitative real-time PCR showed large differences in copy number between Python bivittatus and other snakes, consistent with repeat scanning of whole genome sequences. Copy numbers were significantly higher in female Naja kaouthia than in males, concurring with chromosomal distribution of PBI-DdeI specifically localized to female W chromosomes. PBI-DdeI might act as an evolutionary driver with several repeats to promote W chromosome differentiation and heterochromatinization in N. kaouthia. Analysis revealed PBI-DdeI with a reduced copy number, compared to P. bivittatus, in most snakes studied, and it is possible that it subsequently dispersed and amplified on W chromosomes with different functional roles in N. kaouthia.
The abundance of Akkermansia muciniphila and its relationship with sulphated colonic mucins in health and ulcerative colitis
Authors: Earley Helen , Lennon Grainne , Balfe Áine , Coffey J. Calvin , Winter Desmond C. , O’Connell P. Ronan
Published: October 2019

Akkermansia muciniphila utilises colonic mucin as its substrate. Abundance is reduced in ulcerative colitis (UC), as is the relative proportion of sulphated mucin in the mucus gel layer (MGL). It is unknown if these phenomena are related, however reduced sulphated mucins could contribute to reduced abundance, owing to a lack of substrate. The aim of this study was to quantify A. muciniphila within the MGL and to relate these findings with markers of inflammation and the relative proportion of sulphomucin present. Colonic biopsies and mucus brushings were obtained from 20 patients with active UC (AC), 14 with quiescent UC (QUC) and 20 healthy controls (HC). A. muciniphila abundance was determined by RT-PCR. High iron diamine alcian-blue staining was performed for histological analysis. Patients with AC had reduced abundance of A. muciniphila compared to HC and QUC. A positive association was found between A. muciniphila abundance and higher percentage of sulphated mucin (ρ 0.546, p = 0.000). Lower abundances of A. muciniphila correlated with higher inflammatory scores (ρ = 0.294 (p = 0.001)). This study confirms an inverse relationship between A. muciniphila and inflammation and a positive association between A. muciniphila abundance and percentage of sulfated mucin in the MGL.
Structural determination of Enzyme-Graphene Nanocomposite Sensor Material
Authors: Rai Durgesh K. , Gurusaran Manickam , Urban Volker , Aran Kiana , Ma Lulu , Li Pingzuo , Qian Shuo , Narayanan Tharangattu N. , Ajayan Pulickel M. , Liepmann Dorian , Sekar Kanagaraj , Álvarez-Cao María-Efigenia , Escuder-Rodríguez Juan-José , Cerdán María-Esperanza , González-Siso María-Isabel , Viswanathan Sowmya , Paulmurugan Ramasamy , Renugopalakrishnan Venkatesan
Published: October 2019

State-of-the-art ultra-sensitive blood glucose-monitoring biosensors, based on glucose oxidase (GOx) covalently linked to a single layer graphene (SLG), will be a valuable next generation diagnostic tool for personal glycemic level management. We report here our observations of sensor matrix structure obtained using a multi-physics approach towards analysis of small-angle neutron scattering (SANS) on graphene-based biosensor functionalized with GOx under different pH conditions for various hierarchical GOx assemblies within SLG. We developed a methodology to separately extract the average shape of GOx molecules within the hierarchical assemblies. The modeling is able to resolve differences in the average GOx dimer structure and shows that treatment under different pH conditions lead to differences within the GOx at the dimer contact region with SLG. The coupling of different analysis methods and modeling approaches we developed in this study provides a universal approach to obtain detailed structural quantifications, for establishing robust structure-property relationships. This is an essential step to obtain an insight into the structure and function of the GOx-SLG interface for optimizing sensor performance.
Microarray profiling identifies extracellular circulating miRNAs dysregulated in cystic fibrosis
Authors: Ideozu Justin E. , Zhang Xi , Rangaraj Vittobai , McColley Susanna , Levy Hara
Published: October 2019

Extracellular circulating miRNAs (ECmiRNAs) play a crucial role in cell-to-cell communication and serve as non-invasive biomarkers in a wide range of diseases, but their abundance and functional relevance in cystic fibrosis (CF) remain poorly understood. In this study, we employed microarray technology to identify aberrantly expressed plasma ECmiRNAs in CF and elucidate the functional relevance of their targets. Overall, we captured several ECmiRNAs abundantly expressed in CF. Expression levels of 11 ECmiRNAs differed significantly between CF and healthy control (HC) samples (FDR < 0.05, log2 FC≥2). Among these, 10 were overexpressed while only hsa-miR-598-3p was underexpressed in CF. The overexpressed miRNAs included three let-7 family members (hsa-let-7b-5p, hsa-let-7c-5p and hsa-let-7d-5p), three 103/107 family members (hsa-mir-103a-3p; hsa-mir-103b; hsa-mir-107), hsa-miR-486-5p, and other miRNAs. Using in silico methods, we identified 2,505 validated targets of the 11 differentially expressed miRNAs. Hsa-let-7b-5p was the most important hub in the network analysis. The top-ranked validated targets were involved in miRNA biogenesis and gene expression, including AGO1, DICER1, HMGA1, and MYC. The top pathways influenced by all targets were primarily signal transduction pathways associated with CF, including PI3K/Akt-, Wnt/β catenin-, glucocorticoid receptor-, and mTor signaling pathways. Our results suggest ECmiRNAs may be clinically relevant in CF and warrant further study.