bluuebunny/crossref_metadata_2025 huggingface dataset:
Black Hole Accretion in Gamma Ray Bursts
Authors: Janiuk Agnieszka , Bejger Michal , Sukova Petra , Charzynski Szymon
Published: February 2017

We study the structure and evolution of the hyperaccreting disks and outflows in the gamma ray bursts central engines. The torus around a stellar mass black hole is composed of free nucleons, Helium, electron-positron pairs, and is cooled by neutrino emission. Accretion of matter powers the relativistic jets, responsible for the gamma ray prompt emission. The significant number density of neutrons in the disk and outflowing material will cause subsequent formation of heavier nuclei. We study the process of nucleosynthesis and its possible observational consequences. We also apply our scenario to the recent observation of the gravitational wave signal, detected on 14 September 2015 by the two Advanced LIGO detectors, and related to an inspiral and merger of a binary black hole system. A gamma ray burst that could possibly be related with the GW150914 event was observed by the Fermi satellite. It had a duration of about 1 s and appeared about 0.4 s after the gravitational-wave signal. We propose that a collapsing massive star and a black hole in a close binary could lead to the event. The gamma ray burst was powered by a weak neutrino flux produced in the star remnant’s matter. Low spin and kick velocity of the merged black hole are reproduced in our simulations. Coincident gravitational-wave emission originates from the merger of the collapsed core and the companion black hole.
Hydrogel Micro-/Nanosphere Coated by a Lipid Bilayer: Preparation and Microscopic Probing
Authors: Rahni Sarah , Kazakov Sergey
Published: February 2017

The result of polymeric nanogels and lipid vesicles interaction—lipobeads—can be considered as multipurpose containers for future therapeutic applications, such as targeted anticancer chemotherapy with superior tumor response and minimum side effects. In this work, micrometer sized lipobeads were synthesized by two methods: (i) mixing separately prepared microgels made of poly(N-isopropylacrylamide) (PNIPA) and phospholipid vesicles of micrometer or nanometer size and (ii) polymerization within the lipid vesicles. For the first time, a high vacuum scanning electron microscopy was shown to be suitable for a quick validation of the structural organization of wet lipobeads and their constituents without special sample preparation. In particular, the structural difference of microgels prepared by thermal and UV-polymerization in different solvents was revealed and three types of giant liposomes were recognized under high vacuum in conjunction with their size, composition, and method of preparation. Importantly, the substructure of the hydrogel core and multi- and unilamellar constructions of the peripheral lipid part were explicitly distinguished on the SEM images of lipobeads, justifying the spontaneous formation of a lipid bilayer on the surface of microgels and evidencing an energetically favorable structural organization of the hydrogel/lipid bilayer assembly. This key property can facilitate lipobeads’ preparation and decrease technological expenses on their scaled production. The comparison of the SEM imaging with the scanning confocal and atomic force microscopies data are also presented in the discussion.
2′-O-Methyl RNA/Ethylene-Bridged Nucleic Acid Chimera Antisense Oligonucleotides to Induce Dystrophin Exon 45 Skipping
Authors: Lee Tomoko , Awano Hiroyuki , Yagi Mariko , Matsumoto Masaaki , Watanabe Nobuaki , Goda Ryoya , Koizumi Makoto , Takeshima Yasuhiro , Matsuo Masafumi
Published: February 2017

Duchenne muscular dystrophy (DMD) is a fatal muscle-wasting disease characterized by dystrophin deficiency from mutations in the dystrophin gene. Antisense oligonucleotide (AO)-mediated exon skipping targets restoration of the dystrophin reading frame to allow production of an internally deleted dystrophin protein with functional benefit for DMD patients who have out-of-frame deletions. After accelerated US approval of eteplirsen (Exondys 51), which targets dystrophin exon 51 for skipping, efforts are now focused on targeting other exons. For improved clinical benefits, this strategy requires more studies of the delivery method and modification of nucleic acids. We studied a nucleotide with a 2′-O,4′-C-ethylene-bridged nucleic acid (ENA), which shows high nuclease resistance and high affinity for complementary RNA strands. Here, we describe the process of developing a 2′-O-methyl RNA(2′-OMeRNA)/ENA chimera AO to induce dystrophin exon 45 skipping. One 18-mer 2′-OMeRNA/ENA chimera (AO85) had the most potent activity for inducing exon 45 skipping in cultured myotubes. AO85 was administered to mdx mice without significant side effects. AO85 transfection into cultured myotubes from 13 DMD patients induced exon 45 skipping in all samples at different levels and dystrophin expression in 11 patients. These results suggest the possible efficacy of AO-mediated exon skipping changes in individual patients and highlight the 2′-OMeRNA/ENA chimera AO as a potential fundamental treatment for DMD.
Primetime for Learning Genes
Authors: Keifer Joyce
Published: February 2017

Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be “poised” for rapid response to activate or repress gene expression depending on environmental stimuli.
Characterizing Degradation Gradients through Land Cover Change Analysis in Rural Eastern Cape, South Africa
Authors: Münch Zahn , Okoye Perpetua , Gibson Lesley , Mantel Sukhmani , Palmer Anthony
Published: February 2017

Land cover change analysis was performed for three catchments in the rural Eastern Cape, South Africa, for two time steps (2000 and 2014), to characterize landscape conversion trajectories for sustained landscape health. Land cover maps were derived: (1) from existing data (2000); and (2) through object-based image analysis (2014) of Landsat 8 imagery. Land cover change analysis was facilitated using land cover labels developed to identify landscape change trajectories. Land cover labels assigned to each intersection of the land cover maps at the two time steps provide a thematic representation of the spatial distribution of change. While land use patterns are characterized by high persistence (77%), the expansion of urban areas and agriculture has occurred predominantly at the expense of grassland. The persistence and intensification of natural or invaded wooded areas were identified as a degradation gradient within the landscape, which amounted to almost 10% of the study area. The challenge remains to determine significant signals in the landscape that are not artefacts of error in the underlying input data or scale of analysis. Systematic change analysis and accurate uncertainty reporting can potentially address these issues to produce authentic output for further modelling.
Highlighting the Role of Groundwater in Lake– Aquifer Interaction to Reduce Vulnerability and Enhance Resilience to Climate Change
Authors: Yihdego Yohannes , Webb John , Vaheddoost Babak
Published: February 2017

method is presented to analyze the interaction between groundwater and Lake Linlithgow (Australia) as a case study. A simplistic approach based on a “node” representing the groundwater component is employed in a spreadsheet of water balance modeling to analyze and highlight the effect of groundwater on the lake level over time. A comparison is made between the simulated and observed lake levels over a period of time by switching the groundwater “node “on and off. A bucket model is assumed to represent the lake behaviour. Although this study demonstrates the understanding of Lake Linlithgow’s groundwater system, the current model reflects the contemporary understanding of the local groundwater system, illustrates how to go about modeling in data-scarce environments, and provides a means to assess focal areas for future data collection and model improvements. Results show that this approach is convenient for getting first‐hand information on the effect of groundwater on wetland or lake levels through lake water budget computation via a node representing the groundwater component. The method can be used anywhere and the applicability of such a method is useful to put in place relevant adaptation mechanisms for future water resources management, reducing vulnerability and enhancing resilience to climate change within the lake basin.
Effect of Indoor Temperature on Physical Performance in Older Adults during Days with Normal Temperature and Heat Waves
Authors: Lindemann Ulrich , Stotz Anja , Beyer Nina , Oksa Juha , Skelton Dawn , Becker Clemens , Rapp Kilian , Klenk Jochen
Published: February 2017

Indoor temperature is relevant with regard to mortality and heat-related self-perceived health problems. The aim of this study was to describe the association between indoor temperature and physical performance in older adults. Eighty-one older adults (84% women, mean age 80.9 years, standard deviation 6.53) were visited every four weeks from May to October 2015 and additionally during two heat waves in July and August 2015. Indoor temperature, habitual gait speed, chair-rise performance and balance were assessed. Baseline assessment of gait speed was used to create two subgroups (lower versus higher gait speed) based on frailty criteria. The strongest effect of increasing temperature on habitual gait speed was observed in the subgroup of adults with higher gait speed (−0.087 m/s per increase of 10 °C; 95% confidence interval (CI): −0.136; −0.038). The strongest effects on timed chair-rise and balance performance were observed in the subgroup of adults with lower gait speed (2.03 s per increase of 10 °C (95% CI: 0.79; 3.28) and −3.92 s per increase of 10 °C (95% CI: −7.31; −0.52), respectively). Comparing results of physical performance in absentia of a heat wave and during a heat wave, habitual gait speed was negatively affected by heat in the total group and subgroup of adults with higher gait speed, chair-rise performance was negatively affected in all groups and balance was not affected. The study provides arguments for exercise interventions in general for older adults, because a better physical fitness might alleviate impediments of physical capacity and might provide resources for adequate adaptation in older adults during heat stress.
Biomethylation and Volatilization of Arsenic by Model Protozoan Tetrahymena pyriformis under Different Phosphate Regimes
Authors: Yin Xixiang , Wang Lihong , Zhang Zhanchao , Fan Guolan , Liu Jianjun , Sun Kaizhen , Sun Guo-Xin
Published: February 2017

Tetrahymena pyriformis, a freshwater protozoan, is common in aquatic systems. Arsenic detoxification through biotransformation by T. pyriformis is important but poorly understood. Arsenic metabolic pathways (including cellular accumulation, effluxion, biomethylation, and volatilization) of T. pyriformis were investigated at various phosphate concentrations. The total intracellular As concentration increased markedly as the external phosphate concentration decreased. The highest concentration was 168.8 mg·kg−1 dry weight, after exposure to As(V) for 20 h. Inorganic As was dominant at low phosphate concentrations (3, 6, and 15 mg·L−1), but the concentration was much lower at 30 mg·L−1 phosphate, and As(V) contributed only ~7% of total cellular As. Methylated As contributed 84% of total As at 30 mg·L−1 phosphate, and dimethylarsenate (DMAs(V)) was dominant, contributing up to 48% of total As. Cellular As effluxion was detected, including inorganic As(III), methylarsenate (MAs(V)) and DMAs(V). Volatile As was determined at various phosphate concentrations in the medium. All methylated As concentrations (intracellular, extracellular, and volatilized) had significant linear positive relationships with the initial phosphate concentration. To the best of our knowledge, this is the first study of As biotransformation by protozoa at different phosphate concentrations.
Gaseous Air Pollution and the Risk for Stroke Admissions: A Case-Crossover Study in Beijing, China
Authors: Huang Fangfang , Luo Yanxia , Tan Peng , Xu Qin , Tao Lixin , Guo Jin , Zhang Feng , Xie Xueqin , Guo Xiuhua
Published: February 2017

Background: Though increasing evidence supports association between gaseous air pollution and stroke, it remains unclear whether the effects differ in season, sex and age. The aim of this study was to examine the associations of gaseous air pollution with stroke admissions in Beijing, 2013–2014 in different subgroups. Methods: Case-crossover design and conditional logistic regression were used to perform the analyses. We examined the exposure-response relationship between air pollution and stroke. Stratified analyses were performed in different seasons, sex, and age groups. Results: There were 147,624 stroke admissions during the study period. In the whole study period, percent changes of stroke admissions were 0.82% (95% CI: 0.52% to 1.13%) and 0.73% (95% CI: 0.44% to 1.03%) per 10 μg/m3 increase in the same day conentration of nitrogen dioxide (NO2) and sulfur dioxide (SO2). The positive associations were higher in warm seasons and with patients >65 years (p < 0.05). Contrary effects of carbon monoxide (CO) and ozone on stroke admissions were observed in different seasons. Conclusions: NO2 and SO2 were positively associated with stroke admissions, with stronger effects in warm seasons and with patients >65 years. The associations of CO and ozone with stroke admissions differed across seasons.
The Performance Analysis of Space Resection-Aided Pedestrian Dead Reckoning for Smartphone Navigation in a Mapped Indoor Environment
Authors: Chiang Kai-Wei , Liao Jhen-Kai , Huang Shih-Huan , Chang Hsiu-Wen , Chu Chien-Hsun
Published: February 2017

Smartphones have become indispensable in our daily lives. Their various embedded sensors have inspired innovations in mobile applications—especially for indoor navigation. However, the accuracy, reliability and generalizability of navigation all continue to struggle in environments lacking a Global Navigation Satellite System (GNSS). Pedestrian Dead Reckoning (PDR) is a popular method for indoor pedestrian navigation. Unfortunately, due to its fundamental principles, even a small navigation error will amplify itself, step by step, generally leading to the need for supplementary resources to maintain navigation accuracy. Virtually all mobile devices and most robots contain a basic camera sensor, which has led to the popularity of image-based localization, and vice versa. However, all of the image-based localization requires continuous images for uninterrupted positioning. Furthermore, the solutions provided by either image-based localization or a PDR are usually in a relative coordinate system. Therefore, this research proposes a system, which uses space resection-aided PDR with geo-referenced images of a previously mapped environment to enable seamless navigation and solve the shortcomings of PDR and image-based localization, and evaluates the performance of space resection with different assumptions using a smartphone. The indoor mobile mapping system (IMMS) is used for the effective production of geo-referenced images. The preliminary results indicate that the proposed algorithm is suitable for universal pedestrian indoor navigation, achieving the accuracy required for commercial applications.
A Road Map Refinement Method Using Delaunay Triangulation for Big Trace Data
Authors: Tang Luliang , Ren Chang , Liu Zhang , Li Qingquan
Published: February 2017

With the rapid development of urban transportation, people urgently need high-precision and up-to-date road maps. At the same time, people themselves are an important source of road information for detailed map construction, as they can detect real-world road surfaces with GPS devices in the course of their everyday life. Big trace data makes it possible and provides a great opportunity to extract and refine road maps at relatively low cost. In this paper, a new refinement method is proposed for incremental road map construction using big trace data, employing Delaunay triangulation for higher accuracy during the GPS trace stream fusion process. An experiment and evaluation were carried out on the GPS traces collected by taxis in Wuhan, China. The results show that the proposed method is practical and improves upon existing incremental methods in terms of accuracy.
AKT Axis, miR-21, and RECK Play Pivotal Roles in Dihydroartemisinin Killing Malignant Glioma Cells
Authors: Shao Ying-Ying , Zhang Tao-Lan , Wu Lan-Xiang , Zou He-Cun , Li Shuang , Huang Jin , Zhou Hong-Hao
Published: February 2017

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, is known to play important roles in inhibiting proliferation rate, inducing apoptosis, as well as hindering the metastasis and invasion of glioma cells, but the underlying mechanisms are still unclear so far. In this study, methyl thiazolyl tetrazolium (MTT), colony-forming, wound healing, invasion, and apoptosis assays were performed to investigate the effect of DHA on malignant glioma cells. Results showed that DHA induced apoptosis of malignant glioma cells through Protein Kinase B (AKT) axis, induced death of malignant glioma cells by downregulating miR-21, and inhibited the invasion of malignant glioma cells corresponding with up-regulation of the reversion-inducing-cysteine-rich protein with kazal motifs (RECK). These results revealed that AKT axis, miR-21, and RECK play pivotal roles in DHA killing malignant glioma cells, suggesting that DHA is a potential agent for treating glioma.
Recognition of Local DNA Structures by p53 Protein
Authors: Brázda Václav , Coufal Jan
Published: February 2017

p53 plays critical roles in regulating cell cycle, apoptosis, senescence and metabolism and is commonly mutated in human cancer. These roles are achieved by interaction with other proteins, but particularly by interaction with DNA. As a transcription factor, p53 is well known to bind consensus target sequences in linear B-DNA. Recent findings indicate that p53 binds with higher affinity to target sequences that form cruciform DNA structure. Moreover, p53 binds very tightly to non-B DNA structures and local DNA structures are increasingly recognized to influence the activity of wild-type and mutant p53. Apart from cruciform structures, p53 binds to quadruplex DNA, triplex DNA, DNA loops, bulged DNA and hemicatenane DNA. In this review, we describe local DNA structures and summarize information about interactions of p53 with these structural DNA motifs. These recent data provide important insights into the complexity of the p53 pathway and the functional consequences of wild-type and mutant p53 activation in normal and tumor cells.
Cocoa and Grape Seed Byproducts as a Source of Antioxidant and Anti-Inflammatory Proanthocyanidins
Authors: Cádiz-Gurrea María , Borrás-Linares Isabel , Lozano-Sánchez Jesús , Joven Jorge , Fernández-Arroyo Salvador , Segura-Carretero Antonio
Published: February 2017

Phenolic compounds, which are secondary plant metabolites, are considered an integral part of the human diet. Physiological properties of dietary polyphenols have come to the attention in recent years. Especially, proanthocyanidins (ranging from dimers to decamers) have demonstrated potential interactions with biological systems, such as antiviral, antibacterial, molluscicidal, enzyme-inhibiting, antioxidant, and radical-scavenging properties. Agroindustry produces a considerable amount of phenolic-rich sources, and the ability of polyphenolic structures to interacts with other molecules in living organisms confers their beneficial properties. Cocoa wastes and grape seeds and skin byproducts are a source of several phenolic compounds, particularly mono-, oligo-, and polymeric proanthocyanidins. The aim of this work is to compare the phenolic composition of Theobroma cacao and Vitis vinifera grape seed extracts by high pressure liquid chromatography coupled to a quadrupole time-of-flight mass spectrometer and equipped with an electrospray ionization interface (HPLC-ESI-QTOF-MS) and its phenolic quantitation in order to evaluate the proanthocyanidin profile. The antioxidant capacity was measured by different methods, including electron transfer and hydrogen atom transfer-based mechanisms, and total phenolic and flavan-3-ol contents were carried out by Folin–Ciocalteu and Vanillin assays. In addition, to assess the anti-inflammatory capacity, the expression of MCP-1 in human umbilical vein endothelial cells was measured.
Polyphenol Oxidases in Crops: Biochemical, Physiological and Genetic Aspects
Authors: Taranto Francesca , Pasqualone Antonella , Mangini Giacomo , Tripodi Pasquale , Miazzi Monica , Pavan Stefano , Montemurro Cinzia
Published: February 2017

Enzymatic browning is a colour reaction occurring in plants, including cereals, fruit and horticultural crops, due to oxidation during postharvest processing and storage. This has a negative impact on the colour, flavour, nutritional properties and shelf life of food products. Browning is usually caused by polyphenol oxidases (PPOs), following cell damage caused by senescence, wounding and the attack of pests and pathogens. Several studies indicated that PPOs play a role in plant immunity, and emerging evidence suggested that PPOs might also be involved in other physiological processes. Genomic investigations ultimately led to the isolation of PPO homologs in several crops, which will be possibly characterized at the functional level in the near future. Here, focusing on the botanic families of Poaceae and Solanaceae, we provide an overview on available scientific literature on PPOs, resulting in useful information on biochemical, physiological and genetic aspects.
Photoluminescent Gold Nanoclusters in Cancer Cells: Cellular Uptake, Toxicity, and Generation of Reactive Oxygen Species
Authors: Matulionyte Marija , Dapkute Dominyka , Budenaite Laima , Jarockyte Greta , Rotomskis Ricardas
Published: February 2017

In recent years, photoluminescent gold nanoclusters have attracted considerable interest in both fundamental biomedical research and practical applications. Due to their ultrasmall size, unique molecule-like optical properties, and facile synthesis gold nanoclusters have been considered very promising photoluminescent agents for biosensing, bioimaging, and targeted therapy. Yet, interaction of such ultra-small nanoclusters with cells and other biological objects remains poorly understood. Therefore, the assessment of the biocompatibility and potential toxicity of gold nanoclusters is of major importance before their clinical application. In this study, the cellular uptake, cytotoxicity, and intracellular generation of reactive oxygen species (ROS) of bovine serum albumin-encapsulated (BSA-Au NCs) and 2-(N-morpholino) ethanesulfonic acid (MES)capped photoluminescent gold nanoclusters (Au-MES NCs) were investigated. The results showed that BSA-Au NCs accumulate in cells in a similar manner as BSA alone, indicating an endocytotic uptake mechanism while ultrasmall Au-MES NCs were distributed homogeneously throughout the whole cell volume including cell nucleus. The cytotoxicity of BSA-Au NCs was negligible, demonstrating good biocompatibility of such BSA-protected Au NCs. In contrast, possibly due to ultrasmall size and thin coating layer, Au-MES NCs exhibited exposure time-dependent high cytotoxicity and higher reactivity which led to highly increased generation of reactive oxygen species. The results demonstrate the importance of the coating layer to biocompatibility and toxicity of ultrasmall photoluminescent gold nanoclusters.
Pneumonia, Acute Respiratory Distress Syndrome, and Early Immune-Modulator Therapy
Authors: Lee Kyung-Yil
Published: February 2017

Acute respiratory distress syndrome (ARDS) is caused by infectious insults, such as pneumonia from various pathogens or related to other noninfectious events. Clinical and histopathologic characteristics are similar across severely affected patients, suggesting that a common mode of immune reaction may be involved in the immunopathogenesis of ARDS. There may be etiologic substances that have an affinity for respiratory cells and induce lung cell injury in cases of ARDS. These substances originate not only from pathogens, but also from injured host cells. At the molecular level, these substances have various sizes and biochemical characteristics, classifying them as protein substances and non-protein substances. Immune cells and immune proteins may recognize and act on these substances, including pathogenic proteins and peptides, depending upon the size and biochemical properties of the substances (this theory is known as the protein-homeostasis-system hypothesis). The severity or chronicity of ARDS depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, or the repertoire of specific immune cells that control the substances. Therefore, treatment with early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) as soon as possible may reduce aberrant immune responses in the potential stage of ARDS.
Identification of Autophagy-Related Genes and Their Regulatory miRNAs Associated with Celiac Disease in Children
Authors: Comincini Sergio , Manai Federico , Meazza Cristina , Pagani Sara , Martinelli Carolina , Pasqua Noemi , Pelizzo Gloria , Biggiogera Marco , Bozzola Mauro
Published: February 2017

Celiac disease (CD) is a severe genetic autoimmune disorder, affecting about one in 100 people, where the ingestion of gluten leads to damage in the small intestine. Diagnosing CD is quite complex and requires blood tests and intestinal biopsy examinations. Controversy exists regarding making the diagnosis without biopsy, due to the large spectrum of manifesting symptoms; furthermore, small-intestinal gastroscopy examinations have a relatively complex management in the pediatric population. To identify novel molecular markers useful to increase the sensitivity and specificity in the diagnosis of pediatric CD patients, the expression levels of two key autophagy executor genes (ATG7 and BECN1) and their regulatory validated miRNAs (miR-17 and miR-30a, respectively) were analyzed by relative quantitative real-time-PCR on a cohort of confirmed CD patients compared to age-related controls. Among the investigated targets, the non-parametric Mann–Whitney U test and ROC analysis indicated the highest significant association of BECN1 with CD status in the blood, while in intestinal biopsies, all of the investigated sequences were positively associated with CD diagnosis. Nomogram-based analysis showed nearly opposite expression trends in blood compared to intestine tissue, while hierarchical clustering dendrograms enabled identifying CD and control subgroups based on specific genes and miRNA expression signatures. Next, using an established in vitro approach, through digested gliadin administration in Caco-2 cells, we also highlighted that the modulation of miR-17 endogenous levels using enriched exosomes increased the intracellular autophagosome content, thereby altering the autophagic status. Altogether, these results highlighted novel molecular markers that might be useful to increase the accuracy in CD diagnosis and in molecular-based stratification of the patients, further reinforcing the functional involvement of the regulation of the autophagy process within a digestive and autoimmune-related disorder as CD.
A Lipid Emulsion Reverses Toxic-Dose Bupivacaine-Induced Vasodilation during Tyrosine Phosphorylation-Evoked Contraction in Isolated Rat Aortae
Authors: Ok Seong-Ho , Lee Soo , Kwon Seong-Chun , Choi Mun , Shin Il-Woo , Kang Sebin , Park Miyeong , Hong Jeong-Min , Sohn Ju-Tae
Published: February 2017

The goal of this in vitro study was to examine the effect of a lipid emulsion on toxic-dose bupivacaine-induced vasodilation in a model of tyrosine phosphatase inhibitor sodium orthovanadate-induced contraction in endothelium-denuded rat aortae and to elucidate the associated cellular mechanism. The effect of a lipid emulsion on vasodilation induced by a toxic dose of a local anesthetic during sodium orthovanadate-induced contraction was examined. In addition, the effects of various inhibitors, either bupivacaine alone or a lipid emulsion plus bupivacaine, on protein kinase phosphorylation induced by sodium orthovanadate in rat aortic vascular smooth muscle cells was examined. A lipid emulsion reversed the vasodilation induced by bupivacaine during sodium orthovanadate-induced contraction. The lipid emulsion attenuated the bupivacaine-mediated inhibition of the sodium orthovanadate-induced phosphorylation of protein tyrosine, c-Jun NH2-terminal kinase (JNK), myosin phosphatase target subunit 1 (MYPT1), phospholipase C (PLC) γ-1 and extracellular signal-regulated kinase (ERK). These results suggest that a lipid emulsion reverses toxic-dose bupivacaine-induced vasodilation during sodium orthovanadate-induced contraction via the activation of a pathway involving either tyrosine kinase, JNK, Rho-kinase and MYPT1 or tyrosine kinase, PLC γ-1 and ERK, and this reversal is associated with the lipid solubility of the local anesthetic and the induction of calcium sensitization.
In Vitro Characterization of the Two-Stage Non-Classical Reassembly Pathway of S-Layers
Authors: Breitwieser Andreas , Iturri Jagoba , Toca-Herrera Jose-Luis , Sleytr Uwe , Pum Dietmar
Published: February 2017

The recombinant bacterial surface layer (S-layer) protein rSbpA of Lysinibacillus sphaericus CCM 2177 is an ideal model system to study non-classical nucleation and growth of protein crystals at surfaces since the recrystallization process may be separated into two distinct steps: (i) adsorption of S-layer protein monomers on silicon surfaces is completed within 5 min and the amount of bound S-layer protein sufficient for the subsequent formation of a closed crystalline monolayer; (ii) the recrystallization process is triggered—after washing away the unbound S-layer protein—by the addition of a CaCl2 containing buffer solution, and completed after approximately 2 h. The entire self-assembly process including the formation of amorphous clusters, the subsequent transformation into crystalline monomolecular arrays, and finally crystal growth into extended lattices was investigated by quartz crystal microbalance with dissipation (QCM-D) and atomic force microscopy (AFM). Moreover, contact angle measurements showed that the surface properties of S-layers change from hydrophilic to hydrophobic as the crystallization proceeds. This two-step approach is new in basic and application driven S-layer research and, most likely, will have advantages for functionalizing surfaces (e.g., by spray-coating) with tailor-made biological sensing layers.
Tumor Microenvironment, a Paradigm in Hepatocellular Carcinoma Progression and Therapy
Authors: Tahmasebi Birgani Maryam , Carloni Vinicio
Published: February 2017

Hepatocellular carcinoma (HCC) is among the most lethal and prevalent cancers in the human population. Different etiological factors such as hepatitis B and C virus, alcohol and diabetes cause liver injury followed by inflammation, necrosis and hepatocytes proliferation. Continuous cycles of this destructive–regenerative process culminates in liver cirrhosis which is characterized by regenerating nodules that progress to dysplastic nodules and ultimately HCC. Despite its significance, there is only an elemental understanding of the pathogenetic mechanisms, and there are only limited therapeutic options. Therefore, the study of the involved molecular mechanisms can open a new insight to define more effective treatment strategies. A variety of alterations have been reported in HCC patients, particularly the cancer-associated microenvironment components including immune cells, fibroblast cells, endothelial cells and extracellular matrix can support the neoplastic cells to proliferate, growth and invade. This review summarizes the current state of knowledge and highlights the principal challenges that are relevant to controlling this milieu.
Effects of Postnatal Enriched Environment in a Model of Parkinson’s Disease in Adult Rats
Authors: Jungling Adel , Reglodi Dora , Karadi Zsofia , Horvath Gabor , Farkas Jozsef , Gaszner Balazs , Tamas Andrea
Published: February 2017

Environmental enrichment is a widespread neuroprotective strategy during development and also in the mature nervous system. Several research groups have described that enriched environment in adult rats has an impact on the progression of Parkinson’s disease (PD). The aim of our present study was to examine the effects of early, postnatal environmental enrichment after 6-hydroxydopamine-induced (6-OHDA) lesion of the substantia nigra in adulthood. Newborn Wistar rats were divided into control and enriched groups according to their environmental conditions. For environmental enrichment, during the first five postnatal weeks animals were placed in larger cages and exposed to intensive complex stimuli. Dopaminergic cell loss, and hypokinetic and asymmetrical signs were evaluated after inducing PD with unilateral injections of 6-OHDA in three-month-old animals. Treatment with 6-OHDA led to a significant cell loss in the substantia nigra of control animals, however, postnatal enriched circumstances could rescue the dopaminergic cells. Although there was no significant difference in the percentage of surviving cells between 6-OHDA-treated control and enriched groups, the slightly less dopaminergic cell loss in the enriched group compared to control animals resulted in less severe hypokinesia. Our investigation is the first to provide evidence for the neuroprotective effect of postnatal enriched environment in PD later in life.
Preventive Effects of Pentoxifylline on the Development of Colonic Premalignant Lesions in Obese and Diabetic Mice
Authors: Fukuta Kazufumi , Shirakami Yohei , Maruta Akinori , Obara Koki , Iritani Soichi , Nakamura Nobuhiko , Kochi Takahiro , Kubota Masaya , Sakai Hiroyasu , Tanaka Takuji , Shimizu Masahito
Published: February 2017

Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study investigated the effects of PTX on the development of carcinogen-induced colorectal premalignant lesions in obese and diabetic mice. Male C57BL/KsJ-db/db mice, which are severely obese and diabetic, were administered weekly subcutaneous injections of the colonic carcinogen azoxymethane (15 mg/kg body weight) for four weeks and then received drinking water containing 125 or 500 ppm PTX for eight weeks. At the time of sacrifice, PTX administration markedly suppressed the development of premalignant lesions in the colorectum. The levels of oxidative stress markers were significantly decreased in the PTX-treated group compared with those in the untreated control group. In PTX-administered mice, the mRNA expression levels of cyclooxygenase (COX)-2, interleukin (IL)-6, and TNF-α, and the number of proliferating cell nuclear antigen (PCNA)-positive cells in the colonic mucosa, were significantly reduced. These observations suggest that PTX attenuated chronic inflammation and oxidative stress, and prevented the development of colonic tumorigenesis in an obesity-related colon cancer model.
Targeting Angiogenesis in Biliary Tract Cancers: An Open Option
Authors: Simone Valeria , Brunetti Oronzo , Lupo Luigi , Testini Mario , Maiorano Eugenio , Simone Michele , Longo Vito , Rolfo Christian , Peeters Marc , Scarpa Aldo , Azzariti Amalia , Russo Antonio , Ribatti Domenico , Silvestris Nicola
Published: February 2017

Biliary tract cancers (BTCs) are characterized by a bad prognosis and the armamentarium of drugs for their treatment is very poor. Although the inflammatory status of biliary tract represents the first step in the cancerogenesis, the microenvironment also plays a key role in the pathogenesis of BTCs, promoting tumor angiogenesis, invasion and metastasis. Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer. Recent studies evaluated the genomic landscape of BTCs and evidenced that aberrations in several genes enrolled in the pro-angiogenic signaling, such as FGF receptor-2 (FGFR-2), are characteristic of BTCs. New drugs targeting the signaling pathways involved in angiogenesis have been tested in preclinical studies both in vitro and in vivo with promising results. Moreover, several clinical studies tested monoclonal antibodies against VEGF and tyrosine kinase inhibitors targeting the VEGF and the MEK/ERK pathways. Herein, we evaluate both the pathogenic mechanisms of BTCs focused on angiogenesis and the preclinical and clinical data available regarding the use of new anti-angiogenic drugs in these malignancies.
Antiretroviral Treatment in HIV-1-Positive Mothers: Neurological Implications in Virus-Free Children
Authors: Coelho Antonio , Tricarico Paola , Celsi Fulvio , Crovella Sergio
Published: February 2017

Since the worldwide introduction of antiretroviral therapy (ART) in human immunodeficiency virus type 1, HIV-1-positive mothers, together with HIV-1 testing prior to pregnancy, caesarian birth and breastfeeding cessation with replacement feeding, a reduction of HIV-1 mother-to-child transmission (MTCT) has been observed in the last few years. As such, an increasing number of children are being exposed in utero to ART. Several questions have arisen concerning the neurological effects of ART exposure in utero, considering the potential effect of antiretroviral drugs on the central nervous system, a structure which is in continuous development in the fetus and characterized by great plasticity. This review aims at discussing the possible neurological impairment of children exposed to ART in utero, focusing attention on the drugs commonly used for HIV-1 MTCT prevention, clinical reports of ART neurotoxicity in children born to HIV-1-positive mothers, and neurologic effects of protease inhibitors (PIs), especially ritonavir-“boosted” lopinavir (LPV/r) in cell and animal central nervous system models evaluating the potential neurotoxic effect of ART. Finally, we present the findings of a meta-analysis to assess the effects on the neurodevelopment of children exposed to ART in utero.
The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder
Authors: Delhey Leanna , Nur Kilinc Ekim , Yin Li , Slattery John , Tippett Marie , Rose Shannon , Bennuri Sirish , Kahler Stephen , Damle Shirish , Legido Agustin , Goldenthal Michael , Frye Richard
Published: February 2017

Treatment for mitochondrial dysfunction is typically guided by expert opinion with a paucity of empirical evidence of the effect of treatment on mitochondrial activity. We examined citrate synthase and Complex I and IV activities using a validated buccal swab method in 127 children with autism spectrum disorder with and without mitochondrial disease, a portion of which were on common mitochondrial supplements. Mixed-model linear regression determined whether specific supplements altered the absolute mitochondrial activity as well as the relationship between the activities of mitochondrial components. Complex I activity was increased by fatty acid and folate supplementation, but folate only effected those with mitochondrial disease. Citrate synthase activity was increased by antioxidant supplementation but only for the mitochondrial disease subgroup. The relationship between Complex I and IV was modulated by folate while the relationship between Complex I and Citrate Synthase was modulated by both folate and B12. This study provides empirical support for common mitochondrial treatments and demonstrates that the relationship between activities of mitochondrial components might be a marker to follow in addition to absolute activities. Measurements of mitochondrial activity that can be practically repeated over time may be very useful to monitor the biochemical effects of treatments.
Global Aspects of Triazole Resistance in Aspergillus fumigatus with Focus on Latin American Countries
Authors: Gonçalves Sarah
Published: February 2017

Azole resistance in Aspergillus has emerged as an escalating problem in health care, and it has been detected in patients exposed, or not, to these drugs. It is known that azole antifungals are widely applied not only in clinical treatments for fungal infections, but also as agricultural fungicides, resulting in a significant threat for human health. Although the number of cases of azole-resistant aspergillosis is still limited, various resistance mechanisms are described from clinical and environmental isolates. These mechanisms consist mainly of alterations in the target of azole action (CYP51A gene)—specifically on TR34/L98H and TR46/Y121F/T289A, which are responsible for over 90% of resistance cases. This review summarizes the epidemiology, management, and extension of azole resistance in A. fumigatus worldwide and its potential impact in Latin American countries, emphasizing its relevance to clinical practice.
Uniaxial Negative Thermal Expansion and Mechanical Properties of a Zinc-Formate Framework
Authors: Gao Hongqiang , Wei Wenjuan , Li Yizhang , Wu Rong , Feng Guoqiang , Li Wei
Published: February 2017

The thermal expansion behavior of a metal-formate framework, Zn(HCOO)2·2(H2O) (1), has been systematically studied via variable temperature single-crystal X-ray diffraction. Our results demonstrate that this formate exhibits significant negative thermal expansion (NTE, −26(2) MK−1) along its c-axis. Detailed structural analyses reveal that the large NTE response is attributed to the ‘hinge-strut’ like framework motion. In addition, the fundamental mechanical properties of framework 1 have been explored via nanoindentation experiments. The measured elastic modulus and hardness properties on the (00-2)/(100)/(110) facets are 35.5/35.0/27.1 and 2.04/1.83/0.47 GPa, respectively. The stiffness and hardness anisotropy can be correlated well with the underlying framework structure, like its thermoelastic behavior.
Numerical Investigation of the Fracture Mechanism of Defective Graphene Sheets
Authors: Fan Na , Ren Zhenzhou , Jing Guangyin , Guo Jian , Peng Bei , Jiang Hai
Published: February 2017

Despite the unique occurrences of structural defects in graphene synthesis, the fracture mechanism of a defective graphene sheet has not been fully understood due to the complexities of the defects. In this study, the fracture mechanism of the monolayer graphene with four common types of defects (single vacancy defect, divacancy defect, Stone–Wales defect and line vacancy defect) were investigated systematically for mechanical loading along armchair and zigzag directions, by using the finite element method. The results demonstrated that all four types of defects could cause significant fracture strength loss in graphene sheet compared with the pristine one. In addition, the results revealed that the stress concentration occurred at the carbon–carbon bonds along the same direction as the displacement loading due to the deficiency or twist of carbon–carbon bonds, resulting in the breaking of the initial crack point in the graphene sheet. The fracture of the graphene sheet was developed following the direction of the breaking of carbon–carbon bonds, which was opposite to that of the displacement loading.
Multicolour Emission States from Charge Transfer between Carbon Dots and Surface Molecules
Authors: Hu Shengliang , Wang Yanbing , Zhang Wenyu , Chang Qing , Yang Jinlong
Published: February 2017

The emissive states of carbon dots have been tuned by controlling the charge transfer process. The carbon dots couple with molecules, which are made of a benzene ring and different heteroatom substituents, through amino-carboxylic bonds that are generally identified as charge transfer promoters at the interface. New ways of radiative recombination are created due to the transfer of photo-excited electrons from carbon dots to the lowest unoccupied molecular orbital (LUMO) of the grafted molecules. By variation of the molecular orbital energy levels via heteroatom substituents in the benzene ring, the different optical properties and emission colors of the carbon dots were presented. This work opens up new opportunities for the application of carbon dots since different heteroatom substituents could lead to many possibilities for conjugation with drugs and biomolecules.
A Bio-Electro-Fenton System Employing the Composite FePc/CNT/SS316 Cathode
Authors: Wang Yi-Ta , Wang Ruei-Shiang
Published: February 2017

Bio-electro-Fenton microbial fuel cells generate energy through the decomposition of organic matter by microorganisms. The generated electricity drives a Fenton reaction in a cathode chamber, which can be used for the decolorization of dye wastewater. Most of the previous works added expensive platinum catalyst to improve the electrical property of the system. In this research, aligned carbon nanotubes (CNTs) were generated on the surface of SS316 stainless steel by chemical vapor deposition, and an iron phthalocyanine (FePc) catalyst was added to fabricate a compound (FePc/CNT/SS316) that was applied to the cathode electrode of the fuel cell system. This was expected to improve the overall electricity generation efficiency and extent of decolorization of the system. The results showed that the maximum current density of the system with the modified electrode was 3206.30 mA/m2, and the maximum power was 726.55 mW/m2, which were increased by 937 and 2594 times, respectively, compared to the current and power densities of a system where only the SS316 stainless steel electrode was used. In addition, the decolorization of RB5 dye reached 84.6% within 12 h. Measurements of the electrical properties of bio-electro-Fenton microbial fuel cells and dye decolorization experiments with the FePc/CNT/SS316 electrode showed good results.
Porosity Effect on Thermal Properties of Al-12 wt % Si/Graphite Composites
Authors: Molina José-Miguel , Rodríguez-Guerrero Alejandro , Louis Enrique , Rodríguez-Reinoso Francisco , Narciso Javier
Published: February 2017

The effect of porosity on the thermal conductivity and the coefficient of thermal expansion of composites obtained by infiltration of Al-12 wt % Si alloy into graphite particulate preforms has been determined. Highly irregular graphite particles were used to fabricate the preforms. The thermal conductivity of these composites gradually increases with the applied infiltration pressure given the inherent reduction in porosity. A simple application of the Hasselman-Johnson model in a two-step procedure (that accounts for the presence of both graphite particles and voids randomly dispersed in a metallic matrix) offers a good estimation of the experimental results. As concerns the coefficient of thermal expansion, the results show a slight increase with saturation being approximately in the range 14.6–15.2 × 10−6 K−1 for a saturation varying from 86% up to 100%. Results lie within the standard Hashin-Strikman bounds.