bluuebunny/crossref_metadata_2025 huggingface dataset:
GRP94 Is Involved in the Lipid Phenotype of Brain Metastatic Cells
Authors: Santana-Codina Naiara , Marcé-Grau Anna , Muixí Laia , Nieva Claudia , Marro Mónica , Sebastián David , Muñoz Juan Pablo , Zorzano Antonio , Sierra Angels
Published: August 2019

Metabolic adaptation may happen in response to the pressure exerted by the microenvironment and is a key step in survival of metastatic cells. Brain metastasis occurs as a consequence of the systemic dissemination of tumor cells, a fact that correlates with poor prognosis and high morbidity due to the difficulty in identifying biomarkers that allow a more targeted therapy. Previously, we performed transcriptomic analysis of human breast cancer patient samples and evaluated the differential expression of genes in brain metastasis (BrM) compared to lung, bone and liver metastasis. Our network approach identified upregulation of glucose-regulated protein 94 (GRP94) as well as proteins related to synthesis of fatty acids (FA) in BrM. Here we report that BrM cells show an increase in FA content and decreased saturation with regard to parental cells measured by Raman spectroscopy that differentiate BrM from other metastases. Moreover, BrM cells exerted a high ability to oxidize FA and compensate hypoglycemic stress due to an overexpression of proteins involved in FA synthesis and degradation (SREBP-1, LXRα, ACOT7). GRP94 ablation restored glucose dependence, down-regulated ACOT7 and SREBP-1 and decreased tumorigenicity in vivo. In conclusion, GRP94 is required for the metabolic stress survival of BrM cells, and it might act as a modulator of lipid metabolism to favor BrM progression.
The Role of Exosomal MicroRNAs in the Tumor Microenvironment of Breast Cancer
Authors: Liu Qingqing , Peng Fu , Chen Jianping
Published: August 2019

Breast cancer, ranking first among women’s cancers worldwide, develops from the breast tissue. Study of the breast tissue is, therefore of great significance to the diagnosis and treatment of breast cancer. Exosomes, acting as an effective communicator between cells, are in the ascendant in recent years. One of the most important cargoes contained in the exosomes is microRNAs, belonging to the non-coding RNA family. When the exosomal microRNAs are absorbed into the intracellular location, most of the microRNAs will act as tumor promoters or suppressors by inhibiting the translation process of the target mRNA, thus affecting the behavior of other stromal cells in the tumor microenvironment. At present, growing research focuses on the different types of donor cell sources, their contribution to cancer, miRNA profiling, their biomarker potential, etc. This review aims to state the function of diverse miRNAs in exosomes medicated cell–cell communication and the potency of some specific enriched miRNAs as molecular markers in clinical trials. We also describe the mechanism of anti-cancer compounds through exosomes and the exploration of artificially engineered techniques that lead miRNA-inhibitors into exosomes for therapeutic use.
H2O2-Based Method for Rapid Detection of Transgene-Free Rice Plants from Segregating CRISPR/Cas9 Genome-Edited Progenies
Authors: Wu Tsung-Meng , Huang Jian-Zhi , Oung Hui-Min , Hsu Yi-Ting , Tsai Yu-Chang , Hong Chwan-Yang
Published: August 2019

Genome-editing techniques such as CRISPR/Cas9 have been widely used in crop functional genomics and improvement. To efficiently deliver the guide RNA and Cas9, most studies still rely on Agrobacterium-mediated transformation, which involves a selection marker gene. However, several limiting factors may impede the efficiency of screening transgene-free genome-edited plants, including the time needed to produce each life cycle, the response to selection reagents, and the labor costs of PCR-based genotyping. To overcome these disadvantages, we developed a simple and high-throughput method based on visual detection of antibiotics-derived H2O2 to verify transgene-free genome-edited plants. In transgenic rice containing hygromycin phosphotransferase (HPT), H2O2 content did not change in the presence of hygromycin B (HyB). In contrast, in transgenic-free rice plants with 10-h HyB treatment, levels of H2O2 and malondialdehyde, indicators of oxidative stress, were elevated. Detection of H2O2 by 3,3′-diaminobenzidine (DAB) staining suggested that H2O2 could be a marker to efficiently distinguish transgenic and non-transgenic plants. Analysis of 24 segregating progenies of an HPT-containing rice plant by RT-PCR and DAB staining verified that DAB staining is a feasible method for detecting transformants and non-transformants. Transgene-free genome-edited plants were faithfully validated by both PCR and the H2O2-based method. Moreover, HyB induced overproduction of H2O2 in leaves of Arabidopsis, maize, tobacco, and tomato, which suggests the potential application of the DAB method for detecting transgenic events containing HPT in a wide range of plant species. Thus, visual detection of DAB provides a simple, cheap, and reliable way to efficiently identify transgene-free genome-edited and HPT-containing transgenic rice.
Sponges of Carboxymethyl Chitosan Grafted with Collagen Peptides for Wound Healing
Authors: Cheng Yu , Hu Zhang , Zhao Yuntao , Zou Zuhao , Lu Sitong , Zhang Bijun , Li Sidong
Published: August 2019

Burns are physically debilitating and potentially fatal injuries. Two marine biomaterials, carboxymethyl chitosan (CMC) and collagen peptides (COP), have emerged as promising burn dressings. In this paper, sponges of carboxymethyl chitosan grafted with collagen peptide (CMC–COP) were prepared by covalent coupling and freeze drying. Scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy were then used to characterize the prepared sponges. To evaluate the wound healing activity of the CMC–COP sponges, in vitro tests including cell viability scratch wound healing and scald wound healing experiments were performed in rabbits. Appearance studies revealed the porous nature of sponges and FTIR spectroscopy demonstrated the successful incorporation of COP into CMC. The in vitro scratch assay showed that treatment with CMC–COP sponges (at 100 μg/mL) had significant effects on scratch closure. For burn wounds treated with CMC–COP, regeneration of the epidermis and collagen fiber deposition was observed on day 7, with complete healing of the epidermis and wound on days 14 and 21, respectively. Based on the pathological examination by hematoxylin and eosinstaining, the CMC–COP group demonstrated pronounced wound healing efficiencies. These results confirmed that the CMC–COP treatment enhanced cell migration and promoted skin regeneration, thereby highlighting the potential application of these sponges in burn care.
The SUMO Pathway in Hematomalignancies and Their Response to Therapies
Authors: Boulanger Mathias , Paolillo Rosa , Piechaczyk Marc , Bossis Guillaume
Published: August 2019

SUMO (Small Ubiquitin-related MOdifier) is a post-translational modifier of the ubiquitin family controlling the function and fate of thousands of proteins. SUMOylation is deregulated in various hematological malignancies, where it participates in both tumorigenesis and cancer cell response to therapies. This is the case for Acute Promyelocytic Leukemias (APL) where SUMOylation, and subsequent destruction, of the PML-RARα fusion oncoprotein are triggered by arsenic trioxide, which is used as front-line therapy in combination with retinoic acid to cure APL patients. A similar arsenic-induced SUMO-dependent degradation was also documented for Tax, a human T-cell lymphotropic virus type I (HTLV1) viral protein implicated in Adult T-cell Leukemogenesis. SUMOylation also participates in Acute Myeloid Leukemia (AML) response to both chemo- and differentiation therapies, in particular through its ability to regulate gene expression. In Multiple Myeloma, many enzymes of the SUMO pathway are overexpressed and their high expression correlates with lower response to melphalan-based chemotherapies. B-cell lymphomas overexpressing the c-Myc oncogene also overexpress most components of the SUMO pathway and are highly sensitive to SUMOylation inhibition. Targeting the SUMO pathway with recently discovered pharmacological inhibitors, alone or in combination with current therapies, might therefore constitute a powerful strategy to improve the treatment of these cancers.
Causative Links between Protein Aggregation and Oxidative Stress: A Review
Authors: Lévy Elise , El Banna Nadine , Baïlle Dorothée , Heneman-Masurel Amélie , Truchet Sandrine , Rezaei Human , Huang Meng-Er , Béringue Vincent , Martin Davy , Vernis Laurence
Published: August 2019

Compelling evidence supports a tight link between oxidative stress and protein aggregation processes, which are noticeably involved in the development of proteinopathies, such as Alzheimer’s disease, Parkinson’s disease, and prion disease. The literature is tremendously rich in studies that establish a functional link between both processes, revealing that oxidative stress can be either causative, or consecutive, to protein aggregation. Because oxidative stress monitoring is highly challenging and may often lead to artefactual results, cutting-edge technical tools have been developed recently in the redox field, improving the ability to measure oxidative perturbations in biological systems. This review aims at providing an update of the previously known functional links between oxidative stress and protein aggregation, thereby revisiting the long-established relationship between both processes.
Ascaroside Pheromones: Chemical Biology and Pleiotropic Neuronal Functions
Authors: Park Jun Young , Joo Hyoe-Jin , Park Saeram , Paik Young-Ki
Published: August 2019

Pheromones are neuronal signals that stimulate conspecific individuals to react to environmental stressors or stimuli. Research on the ascaroside (ascr) pheromones in Caenorhabditis elegans and other nematodes has made great progress since ascr#1 was first isolated and biochemically defined in 2005. In this review, we highlight the current research on the structural diversity, biosynthesis, and pleiotropic neuronal functions of ascr pheromones and their implications in animal physiology. Experimental evidence suggests that ascr biosynthesis starts with conjugation of ascarylose to very long-chain fatty acids that are then processed via peroxisomal β-oxidation to yield diverse ascr pheromones. We also discuss the concentration and stage-dependent pleiotropic neuronal functions of ascr pheromones. These functions include dauer induction, lifespan extension, repulsion, aggregation, mating, foraging and detoxification, among others. These roles are carried out in coordination with three G protein-coupled receptors that function as putative pheromone receptors: SRBC-64/66, SRG-36/37, and DAF-37/38. Pheromone sensing is transmitted in sensory neurons via DAF-16-regulated glutamatergic neurotransmitters. Neuronal peroxisomal fatty acid β-oxidation has important cell-autonomous functions in the regulation of neuroendocrine signaling, including neuroprotection. In the future, translation of our knowledge of nematode ascr pheromones to higher animals might be beneficial, as ascr#1 has some anti-inflammatory effects in mice. To this end, we propose the establishment of pheromics (pheromone omics) as a new subset of integrated disciplinary research area within chemical ecology for system-wide investigation of animal pheromones.
Aedes albopictus Adult Medium Mass Rearing for SIT Program Development
Authors: Damiens David , Marquereau Lucie , Lebon Cyrille , Le Goff Gilbert , Gaudillat Benjamin , Habchi-Hanriot Nausicaa , Gouagna Louis-Clément
Published: August 2019

For the production of several hundred thousands of Aedes albopictus sterile males for the implementation of a Sterile Insect Technique (SIT) program, no costly mass-rearing equipment is needed during the initial phases, as optimized rearing at laboratory scale can be sufficient for the first steps. The aim of this study was to maximize the egg production by optimizing adult rearing methods for Ae. albopictus. The effect of parameters such as male/female ratio, density of adults, membrane type for blood feeding, quantity of blood delivered, continuous or discontinuous blood feeding, and surface of substrates for egg laying on overall egg production was tested to find optimized conditions. Based on the number of eggs produced per cage in response to the parameters tested, the optimum cage set-up was seen to be 1500 adults in a 30 × 30 × 30 cm cage with a male/female sex ratio of 1:3, fed by fresh bovine blood for periods of 30 min using a cellulose membrane covering a 10 cm stainless steel plate heated by a Hemotek device, and the provision of five oviposition cups to collect eggs. With this set-up, production per cage can reach a maximum of 35,000 eggs per week.
Deciphering Hydrodynamic and Drug-Resistant Behaviors of Metastatic EMT Breast Cancer Cells Moving in a Constricted Microcapillary
Authors: Nath Binita , Bidkar Anil P. , Kumar Vikash , Dalal Amaresh , Jolly Mohit Kumar , Ghosh Siddhartha S. , Biswas Gautam
Published: August 2019

Epithelial to mesenchymal transition (EMT) induces cell migration, invasion, and drug resistance, and consequently, contributes to cancer metastasis and disease aggressiveness. This study attempted to address crucial biological parameters to correlate EMT and drug-treated cancer cells traversing through microcapillaries, reminiscent of metastatic conditions. MDA-MB-468 breast cancer cells induced to undergo EMT by treatment with 20 ng/mL of epidermal growth factor (EGF) were initially passed through several blockages and then through a constricted microchannel, mimicking the flow of invasive metastatic cells through constricted blood microcapillaries. EMT cells acquired enhanced migratory properties and retained 50% viability, even after migration through wells 10–15 μm in size and a constricted passage of 7 μm and 150 μm in length at a constant flow rate of 50 μL/h. The hydrodynamic properties revealed cellular deformation with a deformation index, average transit velocity, and entry time of 2.45, 12.3 mm/s, and 31,000 μs, respectively for a cell of average diameter 19 μm passing through one of the 7 μm constricted sections. Interestingly, cells collected at the channel outlet regained epithelial character, undergoing reverse transition (mesenchymal to epithelial transition, MET) in the absence of EGF. Remarkably, real-time polymerase chain reaction (PCR) analysis confirmed increases of 2- and 2.7-fold in the vimentin and fibronectin expression in EMT cells, respectively; however, their expression reduced to basal level in the MET cells. A scratch assay revealed the pronounced migratory nature of EMT cells compared with MET cells. Furthermore, the number of colonies formed from EMT cells and paclitaxel-treated EMT cells after passing through a constriction were found to be 95 ± 10 and 79 ± 4, respectively, confirming that the EMT cells were more drug resistant with a concomitant two-fold higher expression of the multi-drug resistance (MDR1) gene. Our results highlight the hydrodynamic and drug-evading properties of cells that have undergone an EMT, when passed through a constricted microcapillary that mimics their journey in blood circulation.
Validation of the Hazard and Vulnerability Analysis of Coastal Erosion in the Caribbean and Pacific Coast of Colombia
Authors: Coca-Domínguez Oswaldo , Ricaurte-Villota Constanza
Published: August 2019

A hazard and vulnerability assessment of coastal erosion is an essential first step for planning and decision-making, because it is part of risk management and its results are in the form of easily interpreted traffic-light maps. For the analysis of the assessment in this work, a methodology is proposed which considers three components for both hazard (magnitude, occurrence, and susceptibility) and vulnerability (exposure, fragility, and lack of resilience), through a semi-quantitative approximation, by applying relative indices to different variables. This methodology has been adapted to analyze hazards and vulnerability caused by coastal erosion combining physical and social aspects. For the validation of this methodology, Spratt Bight Beach (Colombian Caribbean) and La Bocana beach (Colombian Pacific) were selected in order to have contrasting regions and to validate the application of the method over a geographical range. One of the most significant outcomes of the assessment of the degree of hazard and vulnerability is that the rating may represent different combinations of factors. It is therefore important to study and interpret the components separately, allowing us to propose corrective and/or prospective focused interventions at local and regional levels. In terms of vulnerability, the assessment highlighted the importance of cultural ecology as a factor of resilience to coastal hazards.
Modeling Analysis and Simulation of Viscous Hydrodynamic Model of Single-DOF Manipulator
Authors: Zhang Minglu , Liu Xiaoyu , Tian Ying
Published: August 2019

Hydrodynamic modeling is the basis of the precise control research of underwater manipulators. Viscous hydrodynamics, an important part of the hydrodynamic model, directly affects the accuracy of the dynamic model and the control model of the manipulator. Considering the limited research on viscous hydrodynamics of underwater manipulators and the difficulty in measuring viscous hydrodynamic coefficients, the viscous hydrodynamic model in the form of Taylor expansion is analyzed and established. Through carrying out simulation calculations, curve fitting and regression analysis, positional derivatives, rotational derivatives, and coupling derivatives in the viscous hydrodynamic model, are determined. This model provides a crucial theoretical foundation and reference data for subsequent related research.
Performances of Using Geopolymers Made with Various Stabilizers for Deep Mixing
Authors: Canakci Hanifi , Güllü Hamza , Alhashemy Ali
Published: August 2019

This research aims to experimentally investigate the potential use of a geopolymer made from various stabilizers or byproducts (fly ash (FA-F, FA-C), slag (SL), glass powder (GP), metakaolin (MK), marble powder (MP), bottom ash (BA), rice husk ash (RHA), silica fume (SF)) to enhance the mechanical performance of soil (clay) via a deep mixing technique. Strengths of geopolymer soilcrete specimens were determined by unconfined compressive strength (UCS) tests regarding curing times (7 to 365 days) by comparing with Portland cement (PC). In addition, ultrasonic pulse velocity (UPV) tests, the effect of molarity (8–16 M), stress-strain behavior, failure modes, and microstructure (SEM, EDX) of geopolymer specimens were examined. Compared to PC, UCS responses of geopolymer specimens yielded: (i) a decreasing trend for FA-F, GP, MK, BA, and MP + FA-F, (ii) an increasing trend for FA-C, SL, and combinations of SL (BA + SL, RHA + SL, SF + SL, MK + SL) favorable with fewer proportions of stabilizers, and (iii) higher increments due to long-term curing (90, 365 days). Despite some decrements, most UCS values were found acceptable (>0.2 MPa) for sufficient enhancement of soft clay. The UCS results were mostly confirmed by UPV performances. The geopolymer specimens were also found to present: (i) strength development for alkaline concentrations from 10 to 14 M, (ii) brittle behavior of stress–strain curves that failed in axial splitting and near axial directions, and (iii) intensity of the silica peak for strength responsibility of the dense microstructure. The findings relatively support the usage of stabilizers or byproducts in the production of geopolymers for potential use in deep mixing. Thus, this research could be a basis for further efforts in this area.
q-Analogue of Differential Subordinations
Authors: Ul-Haq Miraj , Raza Mohsan , Arif Muhammad , Khan Qaiser , Tang Huo
Published: August 2019

In this article, we study differential subordnations in q-analogue. Some properties of analytic functions in q-analogue associated with cardioid domain and limacon domain are considered. In particular, we determine conditions on α such that 1 + α z ∂ q h z h z n ( n = 0 , 1 , 2 , 3 ) are subordinated by Janowski functions and h z ≺ 1 + 4 3 z + 2 3 z 2 . We also consider the same implications such that h z ≺ 1 + 2 z + 1 2 z 2 . We apply these results on analytic functions to find sufficient conditions for q-starlikeness related with cardioid and limacon.
On Some New Weighted Inequalities for Differentiable Exponentially Convex and Exponentially Quasi-Convex Functions with Applications
Authors: Nie Dongming , Rashid Saima , Akdemir Ahmet Ocak , Baleanu Dumitru , Liu Jia-Bao
Published: August 2019

In this article, we aim to establish several inequalities for differentiable exponentially convex and exponentially quasi-convex mapping, which are connected with the famous Hermite–Hadamard (HH) integral inequality. Moreover, we have provided applications of our findings to error estimations in numerical analysis and higher moments of random variables.
Bioactive Brominated Oxindole Alkaloids from the Red Sea Sponge Callyspongia siphonella
Authors: El-Hawary Seham S. , Sayed Ahmed M. , Mohammed Rabab , Hassan Hossam M. , Rateb Mostafa E. , Amin Elham , Mohammed Tarek A. , El-Mesery Mohamed , Bin Muhsinah Abdullatif , Alsayari Abdulrhman , Wajant Harald , Anany Mohamed A. , Abdelmohsen Usama Ramadan
Published: August 2019

In the present study, LC-HRESIMS-assisted dereplication along with bioactivity-guided isolation led to targeting two brominated oxindole alkaloids (compounds 1 and 2) which probably play a key role in the previously reported antibacterial, antibiofilm, and cytotoxicity of Callyspongia siphonella crude extracts. Both metabolites showed potent antibacterial activity against Gram-positive bacteria, Staphylococcus aureus (minimum inhibitory concentration (MIC) = 8 and 4 µg/mL) and Bacillus subtilis (MIC = 16 and 4 µg/mL), respectively. Furthermore, they displayed moderate biofilm inhibitory activity in Pseudomonas aeruginosa (49.32% and 41.76% inhibition, respectively), and moderate in vitro antitrypanosomal activity (13.47 and 10.27 µM, respectively). In addition, they revealed a strong cytotoxic effect toward different human cancer cell lines, supposedly through induction of necrosis. This study sheds light on the possible role of these metabolites (compounds 1 and 2) in keeping fouling organisms away from the sponge outer surface, and the possible applications of these defensive molecules in the development of new anti-infective agents.
Can Anhedonia Be Considered a Suicide Risk Factor? A Review of the Literature
Authors: Bonanni Luca , Gualtieri Flavia , Lester David , Falcone Giulia , Nardella Adele , Fiorillo Andrea , Pompili Maurizio
Published: August 2019

Background and Objectives: At present, data collected from the literature about suicide and anhedonia are controversial. Some studies have shown that low levels of anhedonia are associated with serious suicide attempts and death by suicide, while other studies have shown that high levels of anhedonia are associated with suicide. Materials and Methods: For this review, we searched PubMed, Medline, and ScienceDirect for clinical studies published from 1 January 1990 to 31 December 2018 with the following search terms used in the title or in the abstract: “anhedonia AND suicid*.” We obtained a total of 155 articles; 133 items were excluded using specific exclusion criteria, the remaining 22 articles included were divided into six groups based on the psychiatric diagnosis: mood disorders, schizophrenia spectrum disorders, post-traumatic stress disorder (PTSD), other diagnoses, attempted suicides, and others (healthy subjects). Results: The results of this review reveal inconsistencies. Some studies reported that high anhedonia scores were associated with suicidal behavior (regardless of the diagnosis), while other studies found that low anhedonia scores were associated with suicidal behavior, and a few studies reported no association. The most consistent association between anhedonia and suicidal behavior was found for affective disorders (7 of 7 studies reported a significant positive association) and for PTSD (3 of 3 studies reported a positive association). In the two studies of patients with schizophrenia, one found no association, and one found a negative association. For patients who attempted suicide (undiagnosed), one study found a positive association, one a positive association only for depressed attempters, and one a negative association. Conclusions: We found the most consistent positive association for patients with affective disorders and PTSD, indicating that the assessment of anhedonia may be useful in the evaluation of suicidal risk.
On the Corrosion Behaviour of Low Modulus Titanium Alloys for Medical Implant Applications: A Review
Authors: Afzali Pooria , Ghomashchi Reza , Oskouei Reza H.
Published: August 2019

The corrosion behaviour of new generation titanium alloys (β-type with low modulus) for medical implant applications is of paramount importance due to their possible detrimental effects in the human body such as release of toxic metal ions and corrosion products. In spite of remarkable advances in improving the mechanical properties and reducing the elastic modulus, limited studies have been done on the electrochemical corrosion behaviour of various types of low modulus titanium alloys including the effect of different beta-stabilizer alloying elements. This development should aim for a good balance between mechanical properties, design features, metallurgical aspects and, importantly, corrosion resistance. In this article, we review several significant factors that can influence the corrosion resistance of new-generation titanium alloys such as fabrication process, body electrolyte properties, mechanical treatments, alloying composition, surface passive layer, and constituent phases. The essential factors and their critical features are discussed. The impact of various amounts of α and β phases in the microstructure, their interactions, and their dissolution rates on the surface passive layer and bulk corrosion behaviour are reviewed and discussed in detail. In addition, the importance of different corrosion types for various medical implant applications is addressed in order to specify the significance of every corrosion phenomenon in medical implants.
Recent Applications of Molecularly Imprinted Sol-Gel Methodology in Sample Preparation
Authors: Moein Mohammad Mahdi , Abdel-Rehim Abbi , Abdel-Rehim Mohamed
Published: August 2019

Due to their selectivity and chemical stability, molecularly imprinted polymers have attracted great interest in sample preparation. Imprinted polymers have been applied for the extraction and the enrichment of different sorts of trace analytes in biological and environmental samples before their analysis. Additionally, MIPs are utilized in various sample preparation techniques such as SPE, SPME, SBSE and MEPS. Nevertheless, molecularly imprinted polymers suffer from thermal (stable only up to 150 °C) and mechanical stability issues, improper porosity and poor capacity. The sol-gel methodology as a promising alternative to address these limitations allowing the production of sorbents with controlled porosity and higher surface area. Thus the combination of molecularly imprinted technology and sol-gel technology can create influential materials with high selectivity, high capacity and high thermal stability. This work aims to present an overview of molecularly imprinted sol-gel polymerization methods and their applications in analytical and bioanalytical fields.
Ultrasonic Extraction of Tropane Alkaloids from Radix physochlainae Using as Extractant an Ionic Liquid with Similar Structure
Authors: Yohannes Alula , Zhang Baohui , Dong Bing , Yao Shun
Published: August 2019

In this research, tropane alkaloids in Radix physochlainae were extracted by tropine-type ionic liquid (IL) aqueous solutions under ultrasound assistance, and N-propyltropine hexafluorophosphate ([C3Tr][PF6]) was found to be the most ideal IL in this extraction mode after comprehensive screening. When 0.03 mol/L [C3Tr][PF6] aqueous solution was chosen as the extraction solvent, the solid-liquid ratio of raw material powders and ionic liquid aqueous solution was 1:20 (g/mL), ultrasonic power was 90 W and extraction time was 30 min, the extraction efficiency of tropane alkaloids has reached 121.3%. Compared with common heating extraction, it can further shorten the extraction time, improve extraction efficiency and decrease IL consumption. Furthermore, extraction mechanism together with potential toxicity of IL have been explored and discussed.
First-In-Class Inhibitors Targeting the Interaction between Bacterial RNA Polymerase and Sigma Initiation Factor Affect the Viability and Toxin Release of Streptococcus pneumoniae
Authors: Ye Jiqing , Chu Adrian Jun , Lin Lin , Yang Xiao , Ma Cong
Published: August 2019

Novel antimicrobial classes are in desperate need for clinical management of infections caused by increasingly prevalent multi-drug resistant pathogens. The protein-protein interaction between bacterial RNA polymerase (RNAP) and the housekeeping sigma initiation factor is essential to transcription and bacterial viability. It also presents a potential target for antimicrobial discovery, for which a hit compound (C3) was previously identified from a pharmacophore model-based in silico screen. In this study, the hit compound was experimentally assessed with some rationally designed derivatives for the antimicrobial activities, in particular against Streptococcus pneumoniae and other pathogens. One compound, C3-005, shows dramatically improved activity against pneumococci compared to C3. C3-005 also attenuates S. pneumoniae toxin production more strongly than existing classes of antibiotics tested. Here we demonstrate a newly validated antimicrobial agent to address an overlooked target in the hit-to-lead process, which may pave the way for further antimicrobial development.
A Crude Extract Preparation and Optimization from a Genomically Engineered Escherichia coli for the Cell-Free Protein Synthesis System: Practical Laboratory Guideline
Authors: Kim Jeehye , Copeland Caroline E. , Padumane Sahana R. , Kwon Yong-Chan
Published: August 2019

With the advancement of synthetic biology, the cell-free protein synthesis (CFPS) system has been receiving the spotlight as a versatile toolkit for engineering natural and unnatural biological systems. The CFPS system reassembles the materials necessary for transcription and translation and recreates the in vitro protein synthesis environment by escaping a physical living boundary. The cell extract plays an essential role in this in vitro format. Here, we propose a practical protocol and method for Escherichia coli-derived cell extract preparation and optimization, which can be easily applied to both commercially available and genomically engineered E. coli strains. The protocol includes: (1) The preparation step for cell growth and harvest, (2) the thorough step-by-step procedures for E. coli cell extract preparation including the cell wash and lysis, centrifugation, runoff reaction, and dialysis, (3) the preparation for the CFPS reaction components and, (4) the quantification of cell extract and cell-free synthesized protein. We anticipate that the protocol in this research will provide a simple preparation and optimization procedure of a highly active E. coli cell extract.
The Study of Deep Level Traps and Their Influence on Current Characteristics of InP/InGaAs Heterostructures
Authors: Zhao Xiaohong , Lu Hongliang , Zhao Manli , Zhang Yuming , Zhang Yimen
Published: August 2019

The damage mechanism of proton irradiation in InP/InGaAs heterostructures was studied. The deep level traps were investigated in detail by deep level transient spectroscopy (DLTS), capacitance–voltage (C–V) measurements and SRIM (the stopping and range of ions in matter, Monte Carlo code) simulation for non-irradiated and 3 MeV proton-irradiated samples at a fluence of 5 × 1012 p/cm2. Compared with non-irradiated samples, a new electron trap at EC-0.37 eV was measured by DLTS in post-irradiated samples and was found to be closer to the center of the forbidden band. The trap concentration in bulk, the interface trap charge density and the electron capture cross-section were 4 × 1015 cm−3, 1.8 × 1012 cm−2, and 9.61 × 10−15 cm2, respectively. The deep level trap, acting as a recombination center, resulted in a large recombination current at a lower forward bias and made the forward current increase in InP/InGaAs heterostructures for post-irradiated samples. When the deep level trap parameters were added into the technology computer-aided design (TCAD) simulation tool, the simulation results matched the current–voltage measurements data well, which verifies the validity of the damage mechanism of proton irradiation.
Prebiotics: Mechanisms and Preventive Effects in Allergy
Authors: Brosseau Carole , Selle Amandine , Palmer Debra J. , Prescott Susan L. , Barbarot Sébastien , Bodinier Marie
Published: August 2019

Allergic diseases now affect over 30% of individuals in many communities, particularly young children, underscoring the need for effective prevention strategies in early life. These allergic conditions have been linked to environmental and lifestyle changes driving the dysfunction of three interdependent biological systems: microbiota, epithelial barrier and immune system. While this is multifactorial, dietary changes are of particular interest in the altered establishment and maturation of the microbiome, including the associated profile of metabolites that modulate immune development and barrier function. Prebiotics are non-digestible food ingredients that beneficially influence the health of the host by 1) acting as a fermentable substrate for some specific commensal host bacteria leading to the release of short-chain fatty acids in the gut intestinal tract influencing many molecular and cellular processes; 2) acting directly on several compartments and specifically on different patterns of cells (epithelial and immune cells). Nutrients with prebiotic properties are therefore of central interest in allergy prevention for their potential to promote a more tolerogenic environment through these multiple pathways. Both observational studies and experimental models lend further credence to this hypothesis. In this review, we describe both the mechanisms and the therapeutic evidence from preclinical and clinical studies exploring the role of prebiotics in allergy prevention.
Hormones in Breast Milk and Effect on Infants’ Growth: A Systematic Review
Authors: Mazzocchi Alessandra , Giannì Maria Lorella , Morniroli Daniela , Leone Ludovica , Roggero Paola , Agostoni Carlo , De Cosmi Valentina , Mosca Fabio
Published: August 2019

Breast milk is characterized by a dynamic and complex composition which includes hormones and other bioactive components that could influence infant growth, development, and optimize health. Among the several beneficial effects associated with prolonged breastfeeding, a 13% decrease in the risk of overweight and obesity has been reported. Recent research has focused on breast milk hormones contributing to the appetite and energy balance regulation and adiposity. Accordingly, we conducted a literature systematic review with the aim to provide an update on the effect of leptin, ghrelin, Insulin Growth Factor 1, adiponectin, and insulin on infants’ and children’s growth and body composition. The revised literature reveals contrasting findings concerning the potential role of all these hormones on modeling growth and fat mass apposition and health outcomes later in life. Further studies are needed to gain further insight into the specific role of these bioactive components in metabolic pathways related to body composition. This could help gain a further insight on infants’ growth, both in physiological and pathological settings.
Diet Quality and Water Scarcity: Evidence from a Large Australian Population Health Survey
Authors: Ridoutt Bradley G. , Baird Danielle , Anastasiou Kimberley , Hendrie Gilly A.
Published: August 2019

There is widespread interest in dietary strategies that lower environmental impacts. However, various forms of malnutrition are also widely prevalent. In a first study of its kind, we quantify the water-scarcity footprint and diet quality score of a large (>9000) population of self-selected adult daily diets. Here, we show that excessive consumption of discretionary foods—i.e., energy-dense and nutrient-poor foods high in saturated fat, added sugars and salt, and alcohol—contributes up to 36% of the water-scarcity impacts and is the primary factor differentiating healthier diets with lower water-scarcity footprint from poorer quality diets with higher water-scarcity footprint. For core food groups (fruits, vegetables, etc.), large differences in water-scarcity footprint existed between individual foods, making difficult the amendment of dietary guidelines for water-scarcity impact reduction. Very large reductions in dietary water-scarcity footprint are possible, but likely best achieved though technological change, product reformulation and procurement strategies in the agricultural and food industries.
Cellular MicroRNA Expression Profile of Chicken Macrophages Infected with Newcastle Disease Virus Vaccine Strain LaSota
Authors: Mu Jiaqi , Liu Xinxin , Yu Xibing , Li Junjiao , Fei Yidong , Ding Zhuang , Yin Renfu
Published: August 2019

Vaccines with live, low-virulence Newcastle disease virus (NDV) strains are still the most accepted prevention and control strategies for combating Newcastle disease (ND), a major viral disease that hampers the development of the poultry industry worldwide. However, the mechanism underlying vaccine-mediated innate cell immune responses remains unclear. Here, a high-throughput Illumina sequencing approach was employed to determine cellular miRNA expression profiles in chicken macrophages infected with the LaSota virus, a widely used vaccine strain for mass vaccination programs against ND in poultry. Compared to the control group, 112 and 115 differentially expressed (DE) miRNAs were identified at 24 hpi (hours post inoculation) and 48 hpi, respectively. Meanwhile, 174 DE miRNAs were identified between 24 hpi and 48 hpi. Furthermore, 12 upregulated and 6 downregulated DE miRNAs were observed in common at 24 and 48 hpi compared with 0 hpi. In addition, target prediction and functional analysis of these DE miRNAs revealed significant enrichment for several signaling pathways, especially in the immune-related genes and pathways, such as the RIG-I-like receptor signaling pathway, NOD-like receptor signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway. Our findings not only lay the foundations for further investigating the roles and regulatory mechanisms of miRNA in vaccine-mediated innate cellular immune responses, but also extend new insights into the interactions between the host and NDV infection.
Training and Toolkit Resources to Support Implementation of a Community Pharmacy Fall Prevention Service
Authors: Robinson Jessica M. , Renfro Chelsea P. , Shockley Sarah J. , Blalock Susan J. , Watkins Alicia K. , Ferreri Stefanie P.
Published: August 2019

Community pharmacies are an ideal setting to manage high-risk medications and screen older adults at risk for falls. Appropriate training and resources are needed to successfully implement services in this setting. The purpose of this paper is to identify the key training, tools, and resources to support implementation of fall prevention services. The service was implemented in a network of community pharmacies located in North Carolina. Pharmacies were provided with onboard and longitudinal training, and a project coach. A toolkit contained resources to collect medication information, identify high-risk medications, develop and share recommendations with prescribers, market the service, and educate patients. Project champions at each pharmacy received a nine-question, web-based survey (Qualtrics) to identify usefulness of the training and resources. The quantitative data were analyzed using descriptive statistics. Thirty-one community pharmacies implemented the service. Twenty-three project champions (74%) completed the post-intervention survey. Comprehensive onboard training was rated as more useful than longitudinal training. Resources to identify high-risk medications, develop recommendations, and share recommendations with prescribers were considered most useful. By providing appropriate training and resources to support fall prevention services, community pharmacists can improve patient care as part of their routine workflow.
Influence of Climate on Radial Growth of Black Pine on the Mountain Regions of Southwestern Turkey
Authors: Doğan Mehmet , Köse Nesibe
Published: August 2019

In this study, we identified the most important climate factors affecting the radial growth of black pine at different elevations of the mountain regions of Southwestern Turkey (Sandıras Mountain, Muğla/Turkey). We used four black pine tree-ring chronologies, which represent upper and lower distribution limits of black pine forest on the South and North slopes of Sandıras Mountain. The relationships between tree-ring width and climate were identified using response function analysis. We performed hierarchical cluster analysis to classify the response functions into meaningful groups. Black pine trees in the mountain regions of Southwestern Turkey responded positively to a warmer temperature and high precipitation at the beginning of the growing season. As high summer temperatures exacerbated drought, radial growth was affected negatively. Hierarchical cluster analysis made clear that elevation differences, rather than aspect, was the main factor responsible for the formation of the clusters. Due to the mountainous terrain of the study area, the changing climatic conditions (air temperature and precipitation) affected the tree-ring widths differently depending on elevation.
Modeling and Simulation of Crystallization of Metal–Organic Frameworks
Authors: Dighe Anish V. , Nemade Roshan Y. , Singh Meenesh R.
Published: August 2019

Metal–organic frameworks (MOFs) are the porous, crystalline structures made of metal–ligands and organic linkers that have applications in gas storage, gas separation, and catalysis. Several experimental and computational tools have been developed over the past decade to investigate the performance of MOFs for such applications. However, the experimental synthesis of MOFs is still empirical and requires trial and error to produce desired structures, which is due to a limited understanding of the mechanism and factors affecting the crystallization of MOFs. Here, we show for the first time a comprehensive kinetic model coupled with population balance model to elucidate the mechanism of MOF synthesis and to estimate size distribution of MOFs growing in a solution of metal–ligand and organic linker. The oligomerization reactions involving metal–ligand and organic linker produce secondary building units (SBUs), which then aggregate slowly to yield MOFs. The formation of secondary building units (SBUs) and their evolution into MOFs are modeled using detailed kinetic rate equations and population balance equations, respectively. The effect of rate constants, aggregation frequency, the concentration of organic linkers, and concurrent crystallization of organic linkers are studied on the dynamics of SBU and MOF formation. The results qualitatively explain the longer timescales involved in the synthesis of MOF. The fundamental insights gained from modeling and simulation analysis can be used to optimize the operating conditions for a higher yield of MOF crystals.
Deep Learning for Soil and Crop Segmentation from Remotely Sensed Data
Authors: Dyson Jack , Mancini Adriano , Frontoni Emanuele , Zingaretti Primo
Published: August 2019

One of the most challenging problems in precision agriculture is to correctly identify and separate crops from the soil. Current precision farming algorithms based on artificially intelligent networks use multi-spectral or hyper-spectral data to derive radiometric indices that guide the operational management of agricultural complexes. Deep learning applications using these big data require sensitive filtering of raw data to effectively drive their hidden layer neural network architectures. Threshold techniques based on the normalized difference vegetation index (NDVI) or other similar metrics are generally used to simplify the development and training of deep learning neural networks. They have the advantage of being natural transformations of hyper-spectral or multi-spectral images that filter the data stream into a neural network, while reducing training requirements and increasing system classification performance. In this paper, to calculate a detailed crop/soil segmentation based on high resolution Digital Surface Model (DSM) data, we propose the redefinition of the radiometric index using a directional mathematical filter. To further refine the analysis, we feed this new radiometric index image of about 3500 × 4500 pixels into a relatively small Convolution Neural Network (CNN) designed for general image pattern recognition at 28 × 28 pixels to evaluate and resolve the vegetation correctly. We show that the result of applying a DSM filter to the NDVI radiometric index before feeding it into a Convolutional Neural Network can potentially improve crop separation hit rate by 65%.
Satellite Earth Observation Data in Epidemiological Modeling of Malaria, Dengue and West Nile Virus: A Scoping Review
Authors: Parselia Elisavet , Kontoes Charalampos , Tsouni Alexia , Hadjichristodoulou Christos , Kioutsioukis Ioannis , Magiorkinis Gkikas , Stilianakis Nikolaos I.
Published: August 2019

Earth Observation (EO) data can be leveraged to estimate environmental variables that influence the transmission cycle of the pathogens that lead to mosquito-borne diseases (MBDs). The aim of this scoping review is to examine the state-of-the-art and identify knowledge gaps on the latest methods that used satellite EO data in their epidemiological models focusing on malaria, dengue and West Nile Virus (WNV). In total, 43 scientific papers met the inclusion criteria and were considered in this review. Researchers have examined a wide variety of methodologies ranging from statistical to machine learning algorithms. A number of studies used models and EO data that seemed promising and claimed to be easily replicated in different geographic contexts, enabling the realization of systems on regional and national scales. The need has emerged to leverage furthermore new powerful modeling approaches, like artificial intelligence and ensemble modeling and explore new and enhanced EO sensors towards the analysis of big satellite data, in order to develop accurate epidemiological models and contribute to the reduction of the burden of MBDs.