bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of Impaired Insulin Signaling to the Pathogenesis of Diabetic Cardiomyopathy
Authors: Zamora Mònica , Villena Josep A.
Published: June 2019

Diabetic cardiomyopathy (DCM) has emerged as a relevant cause of heart failure among the diabetic population. Defined as a cardiac dysfunction that develops in diabetic patients independently of other major cardiovascular risks factors, such as high blood pressure and coronary artery disease, the underlying cause of DCMremains to be unveiled. Several pathogenic factors, including glucose and lipid toxicity, mitochondrial dysfunction, increased oxidative stress, sustained activation of the renin-angiotensin system (RAS) or altered calcium homeostasis, have been shown to contribute to the structural and functional alterations that characterize diabetic hearts. However, all these pathogenic mechanisms appear to stem from the metabolic inflexibility imposed by insulin resistance or lack of insulin signaling. This results in absolute reliance on fatty acids for the synthesis of ATP and impairment of glucose oxidation. Glucose is then rerouted to other metabolic pathways, with harmful effects on cardiomyocyte function. Here, we discuss the role that impaired cardiac insulin signaling in diabetic or insulin-resistant individuals plays in the onset and progression of DCM.
Regulation of Serum Sphingolipids in Andean Children Born and Living at High Altitude (3775 m)
Authors: Barbacini Pietro , Casas Josefina , Torretta Enrica , Capitanio Daniele , Maccallini Gustavo , Hirschler Valeria , Gelfi Cecilia
Published: June 2019

Recent studies on Andean children indicate a prevalence of dyslipidemia and hypertension compared to dwellers at lower altitudes, suggesting that despite similar food intake and daily activities, they undergo different metabolic adaptations. In the present study, the sphingolipid pattern was investigated in serum of 7 underweight (UW), 30 normal weight (NW), 13 overweight (OW), and 9 obese (O) Andean children by liquid chromatography-mass spectrometry (LC-MS). Results indicate that levels of Ceramides (Cers) and sphingomyelins (SMs) correlate positively with biochemical parameters (except for Cers and Vitamin D, which correlate negatively), whereas sphingosine-1-phosphate (S1P) correlates negatively. Correlation results and LC-MS data identify the axis high density lipoprotein-cholesterol (HDL-C), Cers, and S1P as related to hypoxia adaptation. Specifically UW children are characterized by increased levels of S1P compared to O and lower levels of Cers compared to NW children. Furthermore, O children show lower levels of S1P and similar levels of Cers and SMs as NW. In conclusion, our results indicate that S1P is the primary target of hypoxia adaptation in Andean children, and its levels are associated with hypoxia tolerance. Furthermore, S1P can act as marker of increased risk of metabolic syndrome and cardiac dysfunction in young Andeans living at altitude.
Programmed Cell Death-1 Receptor (PD-1)-Mediated Regulation of Innate Lymphoid Cells
Authors: Mallett Grace , Laurence Arian , Amarnath Shoba
Published: June 2019

Programmed cell death-1 (PD-1) is a cell surface receptor that dampens adaptive immune responses. PD-1 is activated by the engagement of its ligands PDL-1 or PDL-2. This results in the inhibition of T cell proliferation, differentiation, cytokine secretion, and cytolytic function. Although a great deal is known about PD-1 mediated regulation of CD4+ and CD8+ T cells, its expression and function in innate lymphoid cells (ILCs) are yet to be fully deciphered. This review summarizes the role of PD-1 in (1) modulating ILC development, (2) ILC function, and (3) PD-1 signaling in ILC. Finally, we explore how PD-1 based immunotherapies may be beneficial in boosting ILC responses in cancer, infections, and other immune-related disorders.
CAR-Based Strategies beyond T Lymphocytes: Integrative Opportunities for Cancer Adoptive Immunotherapy
Authors: Rotolo Ramona , Leuci Valeria , Donini Chiara , Cykowska Anna , Gammaitoni Loretta , Medico Giovanni , Valabrega Giorgio , Aglietta Massimo , Sangiolo Dario
Published: June 2019

Chimeric antigen receptor (CAR)-engineered T lymphocytes (CAR Ts) produced impressive clinical results against selected hematological malignancies, but the extension of CAR T cell therapy to the challenging field of solid tumors has not, so far, replicated similar clinical outcomes. Many efforts are currently dedicated to improve the efficacy and safety of CAR-based adoptive immunotherapies, including application against solid tumors. A promising approach is CAR engineering of immune effectors different from αβT lymphocytes. Herein we reviewed biological features, therapeutic potential, and safety of alternative effectors to conventional CAR T cells: γδT, natural killer (NK), NKT, or cytokine-induced killer (CIK) cells. The intrinsic CAR-independent antitumor activities, safety profile, and ex vivo expansibility of these alternative immune effectors may favorably contribute to the clinical development of CAR strategies. The proper biological features of innate immune response effectors may represent an added value in tumor settings with heterogeneous CAR target expression, limiting the risk of tumor clonal escape. All these properties bring out CAR engineering of alternative immune effectors as a promising integrative option to be explored in future clinical studies.
Biology and Role of Extracellular Vesicles (EVs) in the Pathogenesis of Thrombosis
Authors: Zarà Marta , Guidetti Gianni Francesco , Camera Marina , Canobbio Ilaria , Amadio Patrizia , Torti Mauro , Tremoli Elena , Barbieri Silvia Stella
Published: June 2019

Extracellular vesicles (EVs) are well-established mediators of cell-to-cell communication. EVs can be released by every cell type and they can be classified into three major groups according to their biogenesis, dimension, density, and predominant protein markers: exosomes, microvesicles, and apoptotic bodies. During their formation, EVs associate with specific cargo from their parental cell that can include RNAs, free fatty acids, surface receptors, and proteins. The biological function of EVs is to maintain cellular and tissue homeostasis by transferring critical biological cargos to distal or neighboring recipient cells. On the other hand, their role in intercellular communication may also contribute to the pathogenesis of several diseases, including thrombosis. More recently, their physiological and biochemical properties have suggested their use as a therapeutic tool in tissue regeneration as well as a novel option for drug delivery. In this review, we will summarize the impact of EVs released from blood and vascular cells in arterial and venous thrombosis, describing the mechanisms by which EVs affect thrombosis and their potential clinical applications.
Prediction of Enzyme Function Based on Three Parallel Deep CNN and Amino Acid Mutation
Authors: Gao Ruibo , Wang Mengmeng , Zhou Jiaoyan , Fu Yuhang , Liang Meng , Guo Dongliang , Nie Junlan
Published: June 2019

During the past decade, due to the number of proteins in PDB database being increased gradually, traditional methods cannot better understand the function of newly discovered enzymes in chemical reactions. Computational models and protein feature representation for predicting enzymatic function are more important. Most of existing methods for predicting enzymatic function have used protein geometric structure or protein sequence alone. In this paper, the functions of enzymes are predicted from many-sided biological information including sequence information and structure information. Firstly, we extract the mutation information from amino acids sequence by the position scoring matrix and express structure information with amino acids distance and angle. Then, we use histogram to show the extracted sequence and structural features respectively. Meanwhile, we establish a network model of three parallel Deep Convolutional Neural Networks (DCNN) to learn three features of enzyme for function prediction simultaneously, and the outputs are fused through two different architectures. Finally, The proposed model was investigated on a large dataset of 43,843 enzymes from the PDB and achieved 92.34% correct classification when sequence information is considered, demonstrating an improvement compared with the previous result.
Occurrence and Distribution of Apolygus lucorum on Weed Hosts and Tea Plants in Tea Plantation Ecosystems
Authors: Tian Yueyue , Wang Hanyue , Hou Jian , Zhang Lixia , Zhang Zhengqun , Cai Xiaoming
Published: June 2019

The mirid bugs are one of the most important piercing–sucking insect pests in tea plantations, which severely reduce the quality and economic benefits of tea. In this study, the mirid bug species in the three tea-producing areas in Shandong Province of China were investigated. The distribution and occurrence of dominant species of mirid bugs on four weed host plants and tea plants Camellia sinensis (L.) O. Kuntze (Theaceae) were also studied in the tea agro-ecosystems. The results showed that Apolygus lucorum (Meyer-Dür) (Hemiptera: Miridae) was the dominant mirid bug species in the tea growing areas. Apolygus lucorum densities on Humulus scandens (Lour.) (Moraceae) and Artemisia lavandulaefolia DC. (Asteraceae) were relatively higher than those on Conyza canadensis (Linn) Cronq (Asteraceae), Artemisia annua Linn (Asteraceae), and C. sinensis. Host plant switching of A. lucorum in the tea agro-ecosystem was: A. lucorum scattered on and seriously infested tea plants in June and July; A. lucorum largely migrated to and gathered on H. scandens, A. lavandulaefolia, C. canadensis, and A. annua at the flowering stage, and population densities of A. lucorum on these flowering hosts peaked in late September; in October, A. lucorum gradually moved back to flowering tea plants. These results could provide a reference for selecting host plants, such as Artemisia plants, as trap plants for sustainable control of mirid bugs in tea plantations.
Ocean Surface Anomalies after Strong Winds in the Western Mediterranean Sea
Authors: Ragone Francesco , Meli Andrea , Napoli Anna , Pasquero Claudia
Published: June 2019

The Western Mediterranean Sea is often subject to intense winds, especially during the winter season. Intense winds induce surface cooling associated with anomalous ocean heat loss, upwelling and diapycnal mixing. In this study we investigate the overall impact of extreme wind events on the upper ocean in the Western Mediterranean sea using sea surface temperature and sea surface height observational data products over the period 1993–2014. We show that the largest thermal anomaly is observed a couple of days after the intense wind event and that it is dependent on the wind intensity. During winter, when deep water formation occurs, it persists for over a month. During summer, when the thermocline is very shallow, the recovery time scale is typically less than 10 days. The sea surface height signal reaches a minimum in correspondence to the intense wind, and normal conditions recover in about six weeks. Unlike for intense winds in the tropics associated to the passage of tropical cyclones, no long term sea surface height anomaly is observed, indicating that the water column heat content is not significantly modified. The observed recovery times suggest instead the possibility of feedbacks on the dynamics of intense cyclones at sub-monthly time scales.
Comparing Structural Casualties of the Ro-Ro Vessel Using Straight and Oblique Collision Incidents on the Car Deck
Authors: Prabowo Aditya Rio , Bae Dong Myung , Sohn Jung Min
Published: June 2019

Roll on-roll off (Ro-Ro) ship is the preferable vessel for public transportation and also as a medium to distribute several commodities. Its operations are a straightforward process but traffic management is quite delicate, especially for cross-route. Moreover, maritime incidents sometimes occur, causing significant casualties and in the case of the Ro-Ro, collision with other ship is a possible threat with the ability to trigger immense damages. This research, therefore, was conducted to assess the structural casualties of a Ro-Ro vessel under collision. This was modelled with respect to a ship involved in a certain incident in Indonesia in the latest decade, and the designed collision problems were calculated using the finite element approach. The collision angle was selected as the main input parameter with the straight collision of angle 90° and oblique collision with different angles applied to the scenario. The results found the collision energy due to structural destruction to have distinct pattern and peak value under oblique cases with lower values observed for straight collision for all scenarios. It is, however, recommended that energy should be taken as an initial parameter in further investigation of structural damage and response contour.
Principal Stress Ratio Effect at Residual Stress Determination Utilizing the Variation of Indentation Hardness
Authors: Larsson Per-Lennart
Published: June 2019

The determination of residual stresses is an important issue when it comes to material failure analysis. The variation of global indentation properties, due to the presence of residual stresses, can serve as a guideline for the size and direction of such stresses. One of these global indentation properties, the material hardness, is unfortunately invariant of residual stresses when metals and alloys are at issue. In this situation, one has to rely on the size of the indentation contact area for residual stress determination. For other materials such as ceramics and polymers, where elastic deformations are of greater importance at indentation, such invariance is no longer present. Here, this variation is investigated based on finite element simulations. The aim is then to determine how the indentation hardness is influenced by the principal residual stress ratio and also discuss if such an influence is sufficient in order to determine the size and direction of such stresses in an experimental situation. It should be emphasized that this work does not suggest a new approach to residual stress determination (by indentation testing) but investigates the applicability of previously derived methods to a situation where the surface stress field is not simplified as equi-biaxial or uniaxial. For simplicity, but not out of necessity, only cone indentation of elastic-perfectly plastic materials is considered.
Investigation of the Quench Sensitivity of an AlSi10Mg Alloy in Permanent Mold and High-Pressure Vacuum Die Castings
Authors: Liu Mengyun , Zhang Zhan , Breton Francis , Chen X.-Grant
Published: June 2019

The quench sensitivities of an AlSi10Mg alloy in permanent mold (PM) and high-pressure vacuum die (HPVD) castings were investigated with time–temperature–transformation and time–temperature–property diagrams using an interrupted quench technique. The quench-sensitive temperature range of the HPVD casting sample is 275–450 °C, and its nose temperature is 375 °C. The quench-sensitive range of the PM casting sample is 255–430 °C, and the nose temperature is 350 °C. The mechanical strength versus the cooling rate in both casting samples were predicted via a quench factor analysis and verified experimentally. The critical cooling rate of the HPVD casting sample is 20 °C/s whereas it is 17 °C/s for the PM casting sample. With a shorter critical time, higher nose temperature, and higher critical cooling rate, the HPVD casting sample exhibits a higher quench sensitivity than the PM casting sample. The differences in the quench sensitivities of the AlSi10Mg alloy due to the different casting processes is explained via the different precipitation behavior. At the nose temperature, coarse β-Mg2Si precipitates mainly precipitate along the grain boundaries in the HPVD casting sample, whereas rod-like β-Mg2Si precipitates distribute in the aluminum matrix in the PM casting.
Multidimensional Phononic Bandgaps in Three-Dimensional Lattices for Additive Manufacturing
Authors: Elmadih Waiel , Syam Wahyudin P. , Maskery Ian , Chronopoulos Dimitrios , Leach Richard
Published: June 2019

We report on numerical modelling of three-dimensional lattice structures designed to provide phononic bandgaps. The examined lattice structures rely on two distinct mechanisms for bandgap formation: the destructive interference of elastic waves and internal resonance. Further to the effect of lattice type on the development of phononic bandgaps, we also present the effect of volume fraction, which enables the designer to control the frequency range over which the bandgaps exist. The bandgaps were identified from dispersion curves obtained using a finite element wave propagation modelling technique that provides high computational efficiency and high wave modelling accuracy. We show that lattice structures employing internal resonance can provide transmissibility reduction of longitudinal waves of up to −103 dB. Paired with the manufacturing freedom and material choice of additive manufacturing, the examined lattice structures can be tailored for use in wide-ranging applications including machine design, isolation and support platforms, metrology frames, aerospace and automobile applications, and biomedical devices.
Preparation of Bi2O3/Al Core-Shell Energetic Composite by Two-Step Ball Milling Method and Its Application in Solid Propellant
Authors: Xia Min , Yao Qifa , Yang Huilian , Guo Tao , Du Xiuxin , Zhang Yanjie , Li Guoping , Luo Yunjun
Published: June 2019

In this article, Bi2O3/Al high-density energetic composites with a core-shell structure were prepared by a two-step ball milling method using a common planetary ball milling instrument, and their morphology, structure, and properties were characterized in detail. Through a reasonable ratio design and optimization of the ball milling conditions, the density of the Bi2O3/Al core-shell energetic composite is increased by about 11.3% compared to that of the physical mixed sample under the same conditions. The DSC (Differential Scanning Calorimetry) test also showed that the exothermic quantity of the thermite reaction of the energetic composite reached 2112.21 J/g, which is very close to the theoretical exothermic quantity. The effect of Bi2O3/Al core-shell energetic composite on the energy performance of insensitive HTPE propellant was further studied. The theoretical calculation results showed that replacing the partial Al with Bi2O3/Al core-shell energetic composite can make the density of propellant reach 2.056 g/cm3, and the density specific impulse reach 502.3 s·g/cm3, which is significantly higher than the density and density specific impulse of the conventional composite solid propellant. The thermal test showed that the explosive heat of the HTPE (Hydroxyl terminated polyether) propellant also increased with the increase of the content of Bi2O3/Al core-shell energetic composite.
α-Fe2O3 Nanoparticles/Vermiculite Clay Material: Structural, Optical and Photocatalytic Properties
Authors: Valášková Marta , Tokarský Jonáš , Pavlovský Jiří , Prostějovský Tomáš , Kočí Kamila
Published: June 2019

Photocatalysis is increasingly becoming a center of interest due to its wide use in environmental remediation. Hematite (α-Fe2O3) is one promising candidate for photocatalytic applications. Clay materials as vermiculite (Ver) can be used as a carrier to accommodate and stabilize photocatalysts. Two different temperatures (500 °C and 700 °C) were used for preparation of α-Fe2O3 nanoparticles/vermiculite clay materials. The experimental methods used for determination of structural, optical and photocatalytic properties were X-ray fluorescence (ED-XRF), X-ray diffraction (XRD), scanning electron microscopy (SEM) with energy dispersive X-ray spectrometry (EDS), N2 adsorption method (BET), diffuse reflectance UV-Vis spectroscopy (DRS), photoluminescence spectroscopy (PL) and photocatalytic reduction of CO2, respectively. The data from XRD were confronted with molecular modeling of the material arrangement in the interlayer space of vermiculite structure and the possibility of anchoring the α-Fe2O3 nanoparticles to the surface and edge of vermiculite. Correlations between structural, textural, optical and electrical properties and photocatalytic activity have been studied in detail. The α-Fe2O3 and α-Fe2O3/Ver materials with higher specific surface areas, a smaller crystallite size and structural defects (oxygen vacancies) that a play crucial role in photocatalytic activity, were prepared at a lower calcination temperature of 500 °C.
In Vitro and In Vivo Evaluation of Starfish Bone-Derived β-Tricalcium Phosphate as a Bone Substitute Material
Authors: Ishida Haruka , Haniu Hisao , Takeuchi Akari , Ueda Katsuya , Sano Mahoko , Tanaka Manabu , Takizawa Takashi , Sobajima Atsushi , Kamanaka Takayuki , Saito Naoto
Published: June 2019

We evaluated starfish-derived β-tricalcium phosphate (Sf-TCP) obtained by phosphatization of starfish-bone-derived porous calcium carbonate as a potential bone substitute material. The Sf-TCP had a communicating pore structure with a pore size of approximately 10 μm. Although the porosity of Sf-TCP was similar to that of Cerasorb M (CM)—a commercially available β-TCP bone filler—the specific surface area was roughly three times larger than that of CM. Observation by scanning electron microscopy showed that pores communicated to the inside of the Sf-TCP. Cell growth tests showed that Sf-TCP improved cell proliferation compared with CM. Cells grown on Sf-TCP showed stretched filopodia and adhered; cells migrated both to the surface and into pores. In vivo, vigorous tissue invasion into pores was observed in Sf-TCP, and more fibrous tissue was observed for Sf-TCP than CM. Moreover, capillary formation into pores was observed for Sf-TCP. Thus, Sf-TCP showed excellent biocompatibility in vitro and more vigorous bone formation in vivo, indicating the possible applications of this material as a bone substitute. In addition, our findings suggested that mimicking the microstructure derived from whole organisms may facilitate the development of superior artificial bone.
Wind Turbine Yaw Control Optimization and Its Impact on Performance
Authors: Astolfi Davide , Castellani Francesco , Natili Francesco
Published: June 2019

The optimization of wind energy conversion efficiency has been recently boosting the technology improvement and the scientific comprehension of wind turbines. In this context, the yawing behavior of wind turbines has become a key topic: the yaw control can actually be exploited for optimization at the level of single wind turbine and of wind farm (for example, through active control of wakes). On these grounds, this work is devoted to the study of the yaw control optimization on a 2 MW wind turbine. The upgrade is estimated by analysing the difference between the measured post-upgrade power and a data driven model of the power according to the pre-upgrade behavior. Particular attention has therefore been devoted to the formulation of a reliable model for the pre-upgrade power of the wind turbine of interest, as a function of the operation variables of all the nearby wind turbines in the wind farm: the high correlation between the possible covariates of the model indicates that Principal Component Regression (PCR) is an adequate choice. Using this method, the obtained result for the selected test case is that the yaw control optimization provides a 1% of annual energy production improvement. This result indicates that wind turbine control optimization can non-negligibly improve the efficiency of wind turbine technology.
On the Inverse Ultrahyperbolic Klein-Gordon Kernel
Authors: Nonlaopon Kamsing
Published: June 2019

In this work, we define the ultrahyperbolic Klein-Gordon operator of order α on the function f by T α ( f ) = W α ∗ f , where α ∈ C , W α is the ultrahyperbolic Klein-Gordon kernel, the symbol ∗ denotes the convolution, and f ∈ S , S is the Schwartz space of functions. Our purpose of this work is to study the convolution of W α and obtain the operator L α = T α − 1 such that if T α ( f ) = φ , then L α φ = f .
Terrosamycins A and B, Bioactive Polyether Ionophores from Streptomyces sp. RKND004 from Prince Edward Island Sediment
Authors: Sproule Amanda , Correa Hebelin , Decken Andreas , Haltli Bradley , Berrué Fabrice , Overy David P. , Kerr Russell G.
Published: June 2019

Terrosamycins A (1) and B (2), two polycyclic polyether natural products, were purified from the fermentation broth of Streptomyces sp. RKND004 isolated from Prince Edward Island sediment. The one strain-many compounds (OSMAC) approach coupled with UPLC-HRMS-based metabolomics screening led to the identification of these compounds. The structure of 1 was determined from analysis of NMR, HRMS, and X-ray diffraction data. NMR experiments performed on 2 revealed the presence of two methoxy groups replacing two hydroxy groups in 1. Like other polyether ionophores, 1 and 2 exhibited excellent antibiotic activity against Gram-positive pathogens. Interestingly, the terrosamycins also exhibited activity against two breast cancer cell lines.
SGLT2 Inhibitors: Nephroprotective Efficacy and Side Effects
Authors: Garofalo Carlo , Borrelli Silvio , Liberti Maria , Andreucci Michele , Conte Giuseppe , Minutolo Roberto , Provenzano Michele , De Nicola Luca
Published: June 2019

The burden of diabetic kidney disease (DKD) has increased worldwide in the last two decades. Besides the growth of diabetic population, the main contributors to this phenomenon are the absence of novel nephroprotective drugs and the limited efficacy of those currently available, that is, the inhibitors of renin-angiotensin system. Nephroprotection in DKD therefore remains a major unmet need. Three recent trials testing effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2-i) have produced great expectations on this therapy by consistently evidencing positive effects on hyperglycemia control, and more importantly, on the cardiovascular outcome of type 2 diabetes mellitus. Notably, these trials also disclosed nephroprotective effects when renal outcomes (glomerular filtration rate and albuminuria) were analyzed as secondary endpoints. On the other hand, the use of SGLT2-i can be potentially associated with some adverse effects. However, the balance between positive and negative effects is in favor of the former. The recent results of Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation Study and of other trials specifically testing these drugs in the population with chronic kidney disease, either diabetic or non-diabetic, do contribute to further improving our knowledge of these antihyperglycemic drugs. Here, we review the current state of the art of SGLT2-i by addressing all aspects of therapy, from the pathophysiological basis to clinical effectiveness.
Reduced Carboxylate Graphene Oxide based Field Effect Transistor as Pb2+ Aptamer Sensor
Authors: Li Fang , Wang Zhongrong , Jia Yunfang
Published: June 2019

Aptamer functionalized graphene field effect transistor (apta-GFET) is a versatile bio-sensing platform. However, the chemical inertness of graphene is still an obstacle for its large-scale applications and commercialization. In this work, reduced carboxyl-graphene oxide (rGO-COOH) is studied as a self-activated channel material in the screen-printed apta-GFETs for the first time. Examinations are carefully executed using lead-specific-aptamer as a proof-of-concept to demonstrate its functions in accommodating aptamer bio-probes and promoting the sensing reaction. The graphene-state, few-layer nano-structure, plenty of oxygen-containing groups and enhanced LSA immobilization of the rGO-COOH channel film are evidenced by X-ray photoelectron spectroscopy, Raman spectrum, UV-visible absorbance, atomic force microscopy and scanning electron microscope. Based on these characterizations, as well as a site-binding model based on solution-gated field effect transistor (SgFET) working principle, theoretical deductions for rGO-COOH enhanced apta-GFETs’ response are provided. Furthermore, detections for disturbing ions and real samples demonstrate the rGO-COOH channeled apta-GFET has a good specificity, a limit-of-detection of 0.001 ppb, and is in agreement with the conventional inductively coupled plasma mass spectrometry method. In conclusion, the careful examinations demonstrate rGO-COOH is a promising candidate as a self-activated channel material because of its merits of being independent of linking reagents, free from polymer residue and compatible with rapidly developed print-electronic technology.
Fugacium Spliced Leader Genes Identified from Stranded RNA-Seq Datasets
Authors: Song Yue , Zaheri Bahareh , Liu Min , Sahu Sunil Kumar , Liu Huan , Chen Wenbin , Song Bo , Morse David
Published: June 2019

Trans-splicing mechanisms have been documented in many lineages that are widely distributed phylogenetically, including dinoflagellates. The spliced leader (SL) sequence itself is conserved in dinoflagellates, although its gene sequences and arrangements have diversified within or across different species. In this study, we present 18 Fugacium kawagutii SL genes identified from stranded RNA-seq reads. These genes typically have a single SL but can contain several partial SLs with lengths ranging from 103 to 292 bp. Unexpectedly, we find the SL gene transcripts contain sequences upstream of the canonical SL, suggesting that generation of mature transcripts will require additional modifications following trans-splicing. We have also identified 13 SL-like genes whose expression levels and length are comparable to Dino-SL genes. Lastly, introns in these genes were identified and a new site for Sm-protein binding was proposed. Overall, this study provides a strategy for fast identification of SL genes and identifies new sequences of F. kawagutii SL genes to supplement our understanding of trans-splicing.
The Non-Coding RNA Journal Club: Highlights on Recent Papers—7
Authors: Xiao Hua , Shiu Patrick , Gabryleska Marta , Conn Simon , Dey Abhishek , Chakrabarti Kausik , Regouc Manuel , Pichler Martin , Ørom Ulf , Santulli Gaetano , Nishiwada Satoshi , Goel Ajay , Nagarajan Vaishnavi , Timmons Lisa , Alahari Suresh , Laprovitera Noemi , Ferracin Manuela , Hu Po , Jin Hailing
Published: June 2019

We are delighted to share with you our seventh Journal Club and highlight some of the most interesting papers published recently [...]
Dietary Supplements of Shiikuwasha Extract Attenuates Osteoarthritis Progression in Meniscal/ligamentous Injury and Obese Rats
Authors: Yen Yu-Wen , Lai Ying-Jiun , Kong Zwe-Ling
Published: June 2019

Osteoarthritis (OA), also called degenerative joint disease, is characterized by joint cartilage loss and is strongly linked to obesity. Medicine to alleviate pain is currently the only treatment. Shiikuwasha extract (SE) has been reported to possess valuable bioactive substances exhibiting anti-inflammatory, antiobesity, and anticancer effects. Research is limited to the use of SE in the treatment of OA and obesity. We performed both anterior cruciate ligament transections and medial meniscectomies to induce OA on Sprague–Dawley rats after 11 weeks of a high fat diet followed by 9 weeks of oral SE administration (300, 600, and 1500 mg/kg). This study showed that SE treatment could reduce weight gain and joint pain. Additionally, SE significantly decreased triglycerides and total cholesterol in plasma of the S1500 group but increased high-density lipoprotein cholesterol in the plasma of the S600 group. Meanwhile, plasma levels of tumor necrosis factor alpha (TNF-α) was significantly reduced in the S1500 groups. Histopathological findings confirmed administration of SE attenuated cartilage degeneration. Immunohistochemistry examination demonstrated that caspase 3 and phospho-Janus kinase 2 (p-JAK2) expression levels on chondrocytes were downregulated by SE treatment. Our findings demonstrate that SE can alleviate OA progression by improving obesity.
How Patients with IBS Use Low FODMAP Dietary Information Provided by General Practitioners and Gastroenterologists: A Qualitative Study
Authors: Trott Nick , Aziz Imran , Rej Anupam , Surendran Sanders David
Published: June 2019

There is a lack of dietitians trained to deliver the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet (LFD) for irritable bowel syndrome (IBS). Many patients receive nutritional information from general practitioners (GPs) or gastroenterologists (GEs). Since the LFD is dietitian-led, the aim of this research was to qualitatively explore the effects of GP- and GE-delivered LFD information, in IBS self-management. Semi-structured interviews were conducted in a purposive sample of 8 people with IBS (6 female), who used the LFD as their primary treatment. Interpretive Phenomenological Analysis (IPA) was used to develop themes on the lived experience of the participant’s use of LFD information from GPs and GEs. This information was perceived as trustworthy but simplistic; often just ”food lists” with little personalisation to meet individual needs and difficult to apply in ”real life”. The information required substantial interpretation and the familial and social effects of implementation were not addressed in the materials provided. Supplementary digital resources were regarded as more practical but the participants expressed concern in relation to the validity of these materials. The findings in this study support current clinical guidelines proposed by both the National Institute for Health and Care Excellence and the British Dietetic Association that the LFD should be considered a dietitian-led only intervention.
Mobile Phone Text Message Intervention on Diabetes Self-Care Activities, Cardiovascular Disease Risk Awareness, and Food Choices among Type 2 Diabetes Patients
Authors: Nepper Martha J. , McAtee Jennifer R. , Wheeler Lorey , Chai Weiwen
Published: June 2019

This study examines the effects of educational text messages on diabetes self-care activities, cardiovascular disease (CVD) risk awareness, and home food availabilities related to food choices among patients with type 2 diabetes. Quasi-experimental design was used with 40 patients (58.0 ± 10.6 years) in the intervention group and 39 (55.7 ± 12.2 years) in the control group. In addition to the usual care provided for all participants, the intervention group received three educational text messages weekly for 12 weeks. Pre- and post-intervention measures were collected for both groups. Ninety-four percent of the participants receiving text messages indicated the usefulness of this program. The intervention group either maintained the same level or demonstrated small improvements in diabetes self-care activities after the intervention. Significant increases in scores of CVD risk awareness (57% increase; p = 0.04) and availabilities of fresh fruits (320% increase; p = 0.01) and fresh vegetables (250% increase; p = 0.02) in the home and weekly total (16% increase; p = 0.02) and moderate/vigorous (80% increase; p = 0.006) physical activity levels were observed for the intervention group relative to the control group. The pilot results suggest the feasibility and usefulness of the text message program for diabetes education. The study is registered with Clinical Trials.gov (NCT03039569).
Optimization of Polyarginine-Conjugated PEG Lipid Grafted Proliposome Formulation for Enhanced Cellular Association of a Protein Drug
Authors: Tunsirikongkon Amolnat , Pyo Yong-Chul , Kim Dong-Hyun , Lee Sang-Eun , Park Jeong-Sook
Published: June 2019

The purpose of this study was to develop an oral proliposomal powder of protein using poly-l-arginine-conjugated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG) (PLD) for enhancing cellular association upon reconstitution and to compare its effects with a non-grafted and PEGylated formulation. Cationic proliposome (CATL), PLD-grafted CATL (PLD-CATL), PEGylated CATL (PEG CATL), and PLD grafted-PEG CATL (PLD-PEG CATL) were prepared and compared. Successful conjugation between poly-l-arginine and DSPE-PEG was confirmed by 1H NMR and FT-IR. PLD was successfully grafted onto the proliposomal powder during the slurry process. Although reconstituted liposomal sizes of CATL and PLD-CATL were increased by agglomeration, PEGylation reduced the agglomeration and increased the encapsulation. The viabilities of cells treated with both CATL and PLD-CATL formulations were low but increased following PEGylation. With regard to cellular association, PLD-CATL enhanced cellular association/uptake more rapidly than did CATL. Upon PEGylation, PEG CATL showed a lower level of cellular association/uptake compared with CATL while PLD-PEG CATL did not exhibit the rapid cellular association/uptake as seen with PLD-CATL. However, PLD-PEG CATL still enhanced the higher cellular association/uptake than PEG CATL did without PLD. In conclusion, proliposomes with PLD could accelerate cellular association/uptake but also caused high cellular toxicity. PEGylation reduced cellular toxicity and also changed the cellular association pattern of the PLD formulation.
Enhancement of Magnetic Hyperthermia by Mixing Synthetic Inorganic and Biomimetic Magnetic Nanoparticles
Authors: Iglesias Guillermo R. , Jabalera Ylenia , Peigneux Ana , Checa Fernández Blanca Luna , Delgado Ángel V. , Jimenez-Lopez Concepcion
Published: June 2019

In this work we report on the synthesis and characterization of magnetic nanoparticles of two distinct origins, one inorganic (MNPs) and the other biomimetic (BMNPs), the latter based on a process of bacterial synthesis. Each of these two kinds of particles has its own advantages when used separately with biomedical purposes. Thus, BMNPs present an isoelectric point below neutrality (around pH 4.4), while MNPs show a zero-zeta potential at pH 7, and appear to be excellent agents for magnetic hyperthermia. This means that the biomimetic particles are better suited to be loaded with drug molecules positively charged at neutral pH (notably, doxorubicin, for instance) and releasing it at the acidic tumor environment. In turn, MNPs may provide their transport capabilities under a magnetic field. In this study it is proposed to use a mixture of both kinds of particles at two different concentrations, trying to get the best from each of them. We study which mixture performs better from different points of view, like stability and magnetic hyperthermia response, while keeping suitable drug transport capabilities. This composite system is proposed as a close to ideal drug vehicle with added enhanced hyperthermia response.
3D Printing of a Multi-Layered Polypill Containing Six Drugs Using a Novel Stereolithographic Method
Authors: Robles-Martinez Pamela , Xu Xiaoyan , Trenfield Sarah J. , Awad Atheer , Goyanes Alvaro , Telford Richard , Basit Abdul W. , Gaisford Simon
Published: June 2019

Three-dimensional printing (3DP) has demonstrated great potential for multi-material fabrication because of its capability for printing bespoke and spatially separated material conformations. Such a concept could revolutionise the pharmaceutical industry, enabling the production of personalised, multi-layered drug products on demand. Here, we developed a novel stereolithographic (SLA) 3D printing method that, for the first time, can be used to fabricate multi-layer constructs (polypills) with variable drug content and/or shape. Using this technique, six drugs, including paracetamol, caffeine, naproxen, chloramphenicol, prednisolone and aspirin, were printed with different geometries and material compositions. Drug distribution was visualised using Raman microscopy, which showed that whilst separate layers were successfully printed, several of the drugs diffused across the layers depending on their amorphous or crystalline phase. The printed constructs demonstrated excellent physical properties and the different material inclusions enabled distinct drug release profiles of the six actives within dissolution tests. For the first time, this paper demonstrates the feasibility of SLA printing as an innovative platform for multi-drug therapy production, facilitating a new era of personalised polypills.
A Review of Intrinsic Optical Imaging Serial Blockface Histology (ICI-SBH) for Whole Rodent Brain Imaging
Authors: Lefebvre Joël , Delafontaine-Martel Patrick , Lesage Frédéric
Published: June 2019

In recent years, multiple serial histology techniques were developed to enable whole rodent brain imaging in 3-D. The main driving forces behind the emergence of these imaging techniques were the genome-wide atlas of gene expression in the mouse brain, the pursuit of the mouse brain connectome, and the BigBrain project. These projects rely on the use of optical imaging to target neuronal structures with histological stains or fluorescent dyes that are either expressed by transgenic mice or injected at specific locations in the brain. Efforts to adapt the serial histology acquisition scheme to use intrinsic contrast imaging (ICI) were also put forward, thus leveraging the natural contrast of neuronal tissue. This review focuses on these efforts. First, the origin of optical contrast in brain tissue is discussed with emphasis on the various imaging modalities exploiting these contrast mechanisms. Serial blockface histology (SBH) systems using ICI modalities are then reported, followed by a review of some of their applications. These include validation studies and the creation of multimodal brain atlases at a micrometer resolution. The paper concludes with a perspective of future developments, calling for a consolidation of the SBH research and development efforts around the world. The goal would be to offer the neuroscience community a single standardized open-source SBH solution, including optical design, acquisition automation, reconstruction algorithms, and analysis pipelines.
Characterization of Adult Functional Traits of Local Populations and Cultivars of Sandberg Bluegrass and Bottlebrush Squirreltail Perennial Bunchgrasses
Authors: Solomon Juan K. Q.
Published: June 2019

Plant functional traits offer an understanding of the plant’s ability to cope with varying environmental impositions. The objective of this study was to evaluate the above and belowground adult morphological and chemical composition traits of local populations of Sandberg bluegrass (Poa secunda J. Presl) and Bottlebrush squirreltail (Elymus elymoides (Raf.) Swezey) collected in Nevada and their cultivated varieties. A total of six replications (one seedling each) from each population and cultivar of the two native perennial bunchgrasses were used in a randomized complete block design experiment. Each of the six seedlings from each sourced population was transplanted into individual tree pots (28 cm diameter × 61 cm height) containing 20.4 kg of air-dried Orr gravelly sandy loam soil in mid-November, 2015 and remained in the pots for the duration of the study (23 June, 2016). Traits evaluated were, plant height, leaf length, inflorescence length, shoot biomass, forage nutritive value, root morphological traits, and root carbon and nitrogen content. Traits means were considered different at P < 0.05. For Sandberg bluegrass, the cultivar ‘Mountain Home’ and the population from Panther Valley tended to have greater biomass than the population from Button Point but overall, the average of the two cultivars (10.8 g/plant) did not differ in shoot biomass relative to the local populations (7.6 g/plant). For squirreltail, plant height for the George St. Sonoma and Grass Valley populations (71.3 cm) was greater than the cultivars ‘Toe Jam Creek’ and ‘Vale’ (40.5 cm) but cultivars had greater biomass (12.6 g/plant) than the local populations (5.8 g/plant). Total root length and root diameter were not different among the Sanberg bluegrass and squirreltail populations. The results from traits expounded on in this study indicate the closeness of these populations for both species at their adult stage and provide insights for building a unified framework approach among the different agencies and restoration practitioners to aid in plant assemblages for restoration success in the Great Basin and beyond.
Interlaminar Toughening of Epoxy Carbon Fiber Reinforced Laminates: Soluble Versus Non-Soluble Veils
Authors: Ognibene Giulia , Latteri Alberta , Mannino Salvatore , Saitta Lorena , Recca Giuseppe , Scarpa Fabrizio , Cicala Gianluca
Published: June 2019

This work describes the evaluation of different interlaminar veils to improve the toughening of epoxy/carbon fiber composites manufactured by resin infusion. Three commercial veils have been used in the study: two electro spun thermoplastic nanofiber (Xantulayr® from Revolution Fibres) with different areal weight, and one micro carbon fibers veil (Optiveil® from TFP). Two laboratory made veils were also manufactured by electrospinning commercial polyethersulfone (PES) tougheners (Virantage by Solvay). The veils were selected to be either soluble or non-soluble in the epoxy resin matrix during curing. The solubility was analyzed by scanning electron microscopy and dynamic mechanical analysis testing on the cured laminates. The fracture energy was evaluated by double cantilever bending (DCB) testing under Mode I loading. The insoluble thermoplastic nanofibers showed the highest toughening efficiency, followed by the soluble nanofiber veils. The carbon fiber based veil showed no toughness improvement.
Development of Polyhydroxyalkanoate-Based Polyurethane with Water-Thermal Response Shape-Memory Behavior as New 3D Elastomers Scaffolds
Authors: Wang Cai , Wang Han , Zou Faxing , Chen Shaojun , Wang Yiping
Published: June 2019

In this study, we report the synthesis of a novel bio-based material from polyhydroxyalkanoate (PHA) with good shape-memory effect (SME) and rapid recovery. In this PHA-based polyurethane (PHP), telechelic-hydroxylated polyhydroxyalkanoate (PHA-diols) and polyethylene glycol (PEG) were used as soft segments, providing thermo-responsive domains and water-responsive regions, respectively. Thus, PHP possesses good thermal-responsive SME, such as high shape fixing (>99%) and shape recovery ratio (>90%). Upon immersing in water, the storage modulus of PHP decreased considerably owing to disruption of hydrogen bonds in the PHP matrix. Their water-responsive SME is also suitable for rapid shape recovery (less than 10 s). Furthermore, these outstanding properties can trigger shape-morphing, enabling self-folding and self-expansion of shapes into three-dimensional (3D) scaffolds for potential biomedical applications.