bluuebunny/crossref_metadata_2025 huggingface dataset:
Wildlife in our backyard: interactions between Wied's marmoset Callithrix kuhlii (Primates: Callithrichidae) and residents of Ilhéus, Bahia, Brazil
Authors: Rodrigues Nayara Nascimento , Martinez Romari Alejandra
Published: May 2014

Ecological and behavioral plasticity allow marmosets, genus Callithrix, to adapt and succeed in urban areas. This research assess proximity and relationships between Wied's marmoset Callithrix kuhlii, domestic animals and residents of Ilhéus, Bahia, Brazil. We collected data on the species' urban ecology and biology, since it has been little studied so far. Tools for data gathering included semi‐structured interviews, direct observations and GPS‐mapping. There were sightings within the three major districts of Ilhéus, with 37% of positive questionnaires (n = 359) for marmoset sighting at least weekly. Therefore, marmosets were considered common in this city. Most records and frequent sightings were associated with secondary forest fragments, backyards with fruit trees and mangroves. Marmosets travel among urban fragments using electrical and phone wires and crossing roads. There is a relatively small number of accidents when compared to the number of sightings, with electrocution as the most common. Visitation of marmosets to households, attracted by food provisioning, was considered frequent. People feel pity for the marmosets and lure them to their houses through food, but offered items are not always suitable. Marmoset exploration of uncommon habitats, such as mangroves, might be driven by a lack of larger forest fragments within the city.
Engineered Bovine Antibodies in the Development of Novel Therapeutics, Immunomodulators and Vaccines
Authors: Koti Madhuri , Saini Surinder , Sachan Ashish , Kaushik Azad
Published: May 2014

Some bovine antibodies across all classes are unique, such as the CDR3 of the variable heavy-domain (VH CDR3), which is exceptionally long (up to 66 amino acids), unlike most conventional antibodies where the VH CDR3 loops range from 10 to 25 amino acids. The exceptionally long VH CDR3 is encoded by unusually long germline IGHD genes together with insertion of novel “a” nucleotide rich conserved short nucleotide sequence (CSNS) specifically at the IGH V-D junction. Such an exceptionally long VH CDR3 confers unique “knob and stalk” structural architecture where the knob, formed by intra-VH CDR3 disulfide bridges, is separated by 20 Å solvent exposed stalk composed of anti-parallel beta strands. The substitution of the knob with cytokines, such as, erythropoietin and granulocyte colony stimulating factor 3 (granulocyte colony stimulating factor), results in expression of functional fusion proteins with enhanced pharmacokinetics. The beta stranded stalk can be substituted with other rigid structures, for example, repeat alpha helices to form coiled-coil that mimics the beta-stranded stalk and, thus, opens opportunities for insertion of this structure in the CDRs of antibodies across species. Given the versatility of such a structural platform in bovine antibody VH CDR3, it provides the opportunity for the development of new generation of diagnostics, therapeutics, vaccines and immunomodulating drugs.
β-Lactam Antibiotics Renaissance
Authors: Qin Wenling , Panunzio Mauro , Biondi Stefano
Published: May 2014

Since the 1940s β-lactam antibiotics have been used to treat bacterial infections. However, emergence and dissemination of β-lactam resistance has reached the point where many marketed β-lactams no longer are clinically effective. The increasing prevalence of multidrug-resistant bacteria and the progressive withdrawal of pharmaceutical companies from antibiotic research have evoked a strong reaction from health authorities, who have implemented initiatives to encourage the discovery of new antibacterials. Despite this gloomy scenario, several novel β-lactam antibiotics and β-lactamase inhibitors have recently progressed into clinical trials, and many more such compounds are being investigated. Here we seek to provide highlights of recent developments relating to the discovery of novel β-lactam antibiotics and β-lactamase inhibitors.
Mobilization of Toxic Elements from an Abandoned Manganese Mine in the Arid Metropolitan Las Vegas (NV, USA) Area
Authors: Park Ji , Hodge Vernon , Gerstenberger Shawn , Stave Krystyna
Published: May 2014

Active and abandoned mines may present health risks, especially to children, from environmental exposure to airborne chemical elements, such as Pb, As, and Mn. X-ray fluorescence analysis of tailings at the Three Kids Mine show they contain high levels of: Pb (15,300 mg/kg), As (3690 mg/kg), and Mn (153,000 mg/kg). Soil was sampled along eight transects, radiating from the dried tailings ponds. Concentrations of Mn and Pb to the NE are at background concentrations at 4.8 km, and, As and Sr at 3.2 km from the mine. Going SW to the City of Henderson, all elements are at background at 1.6 cm, with the closest houses at 1.8 km. The United States Environmental Protection Agency (USEPA) Regional Screening Levels (RSLs) are exceeded for Pb, As and Mn at 0.8 km on all transects except one. The RSLs are exceeded for Pb, As and Mn on the NE transects at 1.6 km. Future home sites are on a NE transect between 0.4 km and 2.3 km downwind from the tailings ponds, in an area highly impacted by tailings which exceed the USEPA RSLs. This research demonstrates that there has been the farthest transport of tailings offsite by the prevailing winds to the NE; the closest currently-built homes have not received measurable tailings dust because they are upwind; and that precautions must be taken during the proposed remediation of the mine to restrict dust-transport of Pb, As, and Mn to avoid human exposure and ecological damage.
The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development
Authors: Rymaszewski Amy , Tate Everett , Yimbesalu Joannes , Gelman Andrew , Jarzembowski Jason , Zhang Hao , Pritchard Jr. Kirkwood , Vikis Haris
Published: May 2014

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.
Three Methods for Estimating the Entropy Parameter M Based on a Decreasing Number of Velocity Measurements in a River Cross-Section
Authors: Farina Giulia , Alvisi Stefano , Franchini Marco , Moramarco Tommaso
Published: May 2014

The theoretical development and practical application of three new methods for estimating the entropy parameter M used within the framework of the entropy method proposed by Chiu in the 1980s as a valid alternative to the velocity-area method for measuring the discharge in a river is here illustrated. The first method is based on reproducing the cumulative velocity distribution function associated with a flood event and requires measurements regarding the entire cross-section, whereas, in the second and third method, the estimate of M is based on reproducing the cross-sectional mean velocity by following two different procedures. Both of them rely on the entropy parameter M alone and look for that value of M that brings two different estimates of , obtained by using two different M-dependent-approaches, as close as possible. From an operational viewpoint, the acquisition of velocity data becomes increasingly simplified going from the first to the third approach, which uses only one surface velocity measurement. The procedures proposed are applied in a case study based on the Ponte Nuovo hydrometric station on the Tiber River in central Italy.
Measuring Instantaneous and Spectral Information Entropies by Shannon Entropy of Choi-Williams Distribution in the Context of Electroencephalography
Authors: Melia Umberto , Claria Francesc , Vallverdu Montserrat , Caminal Pere
Published: May 2014

The theory of Shannon entropy was applied to the Choi-Williams time-frequency distribution (CWD) of time series in order to extract entropy information in both time and frequency domains. In this way, four novel indexes were defined: (1) partial instantaneous entropy, calculated as the entropy of the CWD with respect to time by using the probability mass function at each time instant taken independently; (2) partial spectral information entropy, calculated as the entropy of the CWD with respect to frequency by using the probability mass function of each frequency value taken independently; (3) complete instantaneous entropy, calculated as the entropy of the CWD with respect to time by using the probability mass function of the entire CWD; (4) complete spectral information entropy, calculated as the entropy of the CWD with respect to frequency by using the probability mass function of the entire CWD. These indexes were tested on synthetic time series with different behavior (periodic, chaotic and random) and on a dataset of electroencephalographic (EEG) signals recorded in different states (eyes-open, eyes-closed, ictal and non-ictal activity). The results have shown that the values of these indexes tend to decrease, with different proportion, when the behavior of the synthetic signals evolved from chaos or randomness to periodicity. Statistical differences (p-value < 0.0005) were found between values of these measures comparing eyes-open and eyes-closed states and between ictal and non-ictal states in the traditional EEG frequency bands. Finally, this paper has demonstrated that the proposed measures can be useful tools to quantify the different periodic, chaotic and random components in EEG signals.
Development of a Direct Methanol Fuel Cell with Lightweight Disc Type Current Collectors
Authors: Kuan Yean-Der , Lee Shin-Min , Sung Ming-Feng
Published: May 2014

The direct methanol fuel cell (DMFC) adopts methanol solution as a fuel suitable for low power portable applications. A miniature, lightweight, passive air-breathing design is therefore desired. This paper presents a novel planar disc-type DMFC with multiple cells containing a novel developed lightweight current collector at both the anode and cathode sides. The present lightweight current collector adopts FR4 Glass/Epoxy as the substrate with the current collecting areas located at the corresponding membrane electrolyte assembly (MEA) areas. The current collecting areas are fabricated by sequentially coating a corrosion resistant layer and electrical conduction layer via the thermal evaporation technique. The anode current collector has carved flow channels for fuel transport and production. The cathode current collector has drilled holes for passive air breathing. In order to ensure feasibility in the present concept a 3-cell prototype DMFC module with lightweight disc type current collectors is designed and constructed. Experiments were conducted to measure the cell performance. The results show that the highest cell power output is 54.88 mW·cm−2 and successfully demonstrate the feasibility of this novel design.
Equivalent Consumption Minimization Strategy for the Control of Real Driving NOx Emissions of a Diesel Hybrid Electric Vehicle
Authors: Nüesch Tobias , Cerofolini Alberto , Mancini Giorgio , Cavina Nicolò , Onder Christopher , Guzzella Lino
Published: May 2014

Motivated by the fact that the real driving NOx emissions (RDE) of conventional diesel vehicles can exceed the legislation norms by far, a concept for the control of RDE with a diesel parallel hybrid electric vehicle (HEV) is proposed. By extending the well-known equivalent consumption minimization strategy (ECMS), the power split degree of freedom is used to control the NOx emissions and the battery state of charge (SOC) simultaneously. Through an appropriate formulation of the problem, the feedback control is shown to be separable into two dependent PI controllers. By hardware-in-the-loop (HIL) experiments, as well as by simulations, the proposed method is shown to minimize the fuel consumption while tracking a given reference trajectory for both the NOx emissions and the battery SOC.
Software-Defined Networking Using OpenFlow: Protocols, Applications and Architectural Design Choices
Authors: Braun Wolfgang , Menth Michael
Published: May 2014

We explain the notion of software-defined networking (SDN), whose southbound interface may be implemented by the OpenFlow protocol. We describe the operation of OpenFlow and summarize the features of specification versions 1.0–1.4. We give an overview of existing SDN-based applications grouped by topic areas. Finally, we point out architectural design choices for SDN using OpenFlow and discuss their performance implications.
Simulation of Population-Based Commuter Exposure to NO2 Using Different Air Pollution Models
Authors: Ragettli Martina , Tsai Ming-Yi , Braun-Fahrländer Charlotte , De Nazelle Audrey , Schindler Christian , Ineichen Alex , Ducret-Stich Regina , Perez Laura , Probst-Hensch Nicole , Künzli Nino , Phuleria Harish
Published: May 2014

We simulated commuter routes and long-term exposure to traffic-related air pollution during commute in a representative population sample in Basel (Switzerland), and evaluated three air pollution models with different spatial resolution for estimating commute exposures to nitrogen dioxide (NO2) as a marker of long-term exposure to traffic-related air pollution. Our approach includes spatially and temporally resolved data on actual commuter routes, travel modes and three air pollution models. Annual mean NO2 commuter exposures were similar between models. However, we found more within-city and within-subject variability in annual mean (±SD) NO2 commuter exposure with a high resolution dispersion model (40 ± 7 µg m−3, range: 21–61) than with a dispersion model with a lower resolution (39 ± 5 µg m−3; range: 24–51), and a land use regression model (41 ± 5 µg m−3; range: 24–54). Highest median cumulative exposures were calculated along motorized transport and bicycle routes, and the lowest for walking. For estimating commuter exposure within a city and being interested also in small-scale variability between roads, a model with a high resolution is recommended. For larger scale epidemiological health assessment studies, models with a coarser spatial resolution are likely sufficient, especially when study areas include suburban and rural areas.
Improving Protocol Design Feasibility to Drive Drug Development Economics and Performance
Authors: Getz Kenneth
Published: May 2014

Protocol design complexity has increased substantially during the past decade and this in turn has adversely impacted drug development economics and performance. This article reviews the results of two major Tufts Center for the Study of Drug Development studies quantifying the direct cost of conducting less essential and unnecessary protocol procedures and of implementing amendments to protocol designs. Indirect costs including personnel time, work load and cycle time delays associated with complex protocol designs are also discussed. The author concludes with an overview of steps that research sponsors are taking to improve protocol design feasibility.
Does Trading by Small Investors Improve or Deteriorate Price Efficiency? Evidence from the Minimum Trade Unit Changes on the Korea Exchange
Authors: Ahn Hee-Joon
Published: May 2014

In this study, we investigate the effect of minimum trade unit (MTU) reductions on the Korea Exchange (KRX) on price efficiency. The KRX switched its MTU from 10 shares to one share for high-price stocks twice, once in December 2004 and once in July 2006. The MTU changes were intended to attract small individual investors to the markets for high-price stocks. The MTU reductions on the KRX are different from previous cases of MTU reductions in other markets in that the KRX MTU reductions are not chosen by firms but are mandated by the exchange. Using these rare events, we examine whether the reductions in MTU and ensuing small investor participation enhance or deteriorate price efficiency. We examine three variables as indicators of price efficiency: return volatility, residual volatility, and the half-life of return volatility shock estimated from a generalized autoregressive conditional heteroskedasticity (GARCH) model. We find evidence of improved price efficiency from the 2004 event. For the 2004 sample, both return variance and residual return variance declined significantly after the MTU reduction. We also find evidence of reduction, albeit weak, in the half-life of volatility shock for the same sample. Meanwhile, for the 2006 sample, we do not find any changes in return variance or residual variance, nor do we find any evidence of change in the half-life of volatility shock. The difference in the patterns of changes in variables between the 2004 and 2006 events appears to be attributable to differences in the price levels of the stocks that were affected by the MTU changes and, consequently, a difference in reactions by small investors.
Baicalin Inhibits Hypoxia-Induced Pulmonary Artery Smooth Muscle Cell Proliferation via the AKT/HIF-1α/p27-Associated Pathway
Authors: Zhang Lin , Pu Zhichen , Wang Junsong , Zhang Zhifeng , Hu Dongmei , Wang Junjie
Published: May 2014

Baicalin, a flavonoid compound purified from the dry roots of Scutellaria baicalensis Georgi, has been shown to possess various pharmacological actions. Previous studies have revealed that baicalin inhibits the growth of cancer cells through the induction of apoptosis. Pulmonary arterial hypertension (PAH) is a devastating disease characterized by enhanced pulmonary artery smooth muscle cell (PASMCs) proliferation and suppressed apoptosis. However, the potential mechanism of baicalin in the regulation of PASMC proliferation and the prevention of cardiovascular diseases remains unexplored. To test the effects of baicalin on hypoxia, we used rats treated with or without baicalin (100 mg·kg−1 each rat) at the beginning of the third week after hypoxia. Hemodynamic and pulmonary pathomorphology data showed that right ventricular systolic pressures (RVSP), the weight of the right ventricle/left ventricle plus septum (RV/LV + S) ratio and the medial width of pulmonary arterioles were much higher in chronic hypoxia. However, baicalin treatment repressed the elevation of RVSP, RV/LV + S and attenuated the pulmonary vascular structure remodeling (PVSR) of pulmonary arterioles induced by chronic hypoxia. Additionally, baicalin (10 and 20 μmol·L−1) treatment suppressed the proliferation of PASMCs and attenuated the expression of hypoxia-inducible factor-α (HIF-α) under hypoxia exposure. Meanwhile, baicalin reversed the hypoxia-induced reduction of p27 and increased AKT/protein kinase B phosphorylation p-AKT both in vivo and in vitro. These results suggested that baicalin could effectively attenuate PVSR and hypoxic pulmonary hypertension.
Betulinic Acid in Complex with a Gamma-Cyclodextrin Derivative Decreases Proliferation and in Vivo Tumor Development of Non-Metastatic and Metastatic B164A5 Cells
Authors: Soica Codruta , Danciu Corina , Savoiu-Balint Germaine , Borcan Florin , Ambrus Rita , Zupko Istvan , Bojin Florina , Coricovac Dorina , Ciurlea Sorina , Avram Stefana , Dehelean Cristina , Olariu Teodora , Matusz Petru
Published: May 2014

Betulinic acid, a very promising anti-melanoma agent, has very low water solubility that causes low bioavailability. To overcome this inconvenience, a highly water-soluble cyclodextrin was used (octakis-[6-deoxy-6-(2-sulfanyl ethanesulfonic acid)]-γ-cyclodextrin). The complex was physico-chemically analyzed using differential scanning calorimetry (DSC), X-ray and scanning electron microscopy (SEM) methods and then in vitro tested for its antiproliferative activity by the MTT assay and by cell cycle analysis. Finally, the complex was tested in vivo using an animal model of murine melanoma developed in C57BL/6J mice, where it caused a reduction in tumor volume and weight. The study revealed the beneficial influence of betulinic acid inclusion into the cyclodextrin in terms of antiproliferative activity and in vivo tumor development.
Legionella dumoffii Utilizes Exogenous Choline for Phosphatidylcholine Synthesis
Authors: Palusinska-Szysz Marta , Szuster-Ciesielska Agnieszka , Kania Magdalena , Janczarek Monika , Chmiel Elżbieta , Danikiewicz Witold
Published: May 2014

Phosphatidycholine (PC) is the major membrane-forming phospholipid in eukaryotes but it has been found in only a limited number of prokaryotes. Bacteria synthesize PC via the phospholipid N-methylation pathway (Pmt) or via the phosphatidylcholine synthase pathway (Pcs) or both. Here, we demonstrated that Legionella dumoffii has the ability to utilize exogenous choline for phosphatidylcholine (PC) synthesis when bacteria grow in the presence of choline. The Pcs seems to be a primary pathway for synthesis of this phospholipid in L. dumoffii. Structurally different PC species were distributed in the outer and inner membranes. As shown by the LC/ESI-MS analyses, PC15:0/15:0, PC16:0/15:0, and PC17:0/17:1 were identified in the outer membrane and PC14:0/16:0, PC16:0/17:1, and PC20:0/15:0 in the inner membrane. L. dumoffii pcsA gene encoding phosphatidylcholine synthase revealed the highest sequence identity to pcsA of L. bozemanae (82%) and L. longbeachae (81%) and lower identity to pcsA of L. drancourtii (78%) and L. pneumophila (71%). The level of TNF-α in THP1-differentiated cells induced by live and temperature-killed L. dumoffii cultured on a medium supplemented with choline was assessed. Live L. dumoffii bacteria cultured on the choline-supplemented medium induced TNF-α three-fold less efficiently than cells grown on the non-supplemented medium. There is an evident effect of PC modification, which impairs the macrophage inflammatory response.
Effect of Black Soybean Koji Extract on Glucose Utilization and Adipocyte Differentiation in 3T3-L1 Cells
Authors: Huang Chi-Chang , Huang Wen-Ching , Hou Chien-Wen , Chi Yu-Wei , Huang Hui-Yu
Published: May 2014

Adipocyte differentiation and the extent of subsequent fat accumulation are closely related to the occurrence and progression of diseases such as insulin resistance and obesity. Black soybean koji (BSK) is produced by the fermentation of black soybean with Aspergilllus awamori. Previous study indicated that BSK extract has antioxidative and multifunctional bioactivities, however, the role of BSK in the regulation of energy metabolism is still unclear. We aimed to investigate the effect of glucose utilization on insulin-resistant 3T3-L1 preadipocytes and adipogenesis-related protein expression in differentiated adipocytes with BSK treatment. Cytoxicity assay revealed that BSK did not adversely affect cell viability at levels up to 200 µg/mL. The potential for glucose utilization was increased by increased glucose transporter 1 (GLUT1), GLUT4 and protein kinase B (AKT) protein expression in insulin-resistant 3T3-L1 cells in response to BSK treatment. Simultaneously, BSK inhibited lipid droplet accumulation in differentiated 3T3-L1 cells. The inhibitory effect of adipogenesis was associated with downregulated peroxisome proliferator-activated receptor g (PPARγ) level and upregulated Acrp30 protein expression. Our results suggest that BSK extract could improve glucose uptake by modulating GLUT1 and GLUT4 expression in a 3T3-L1 insulin-resistance cell model. In addition, BSK suppressed differentiation and lipid accumulation in mature 3T3-L1 adipocytes, which may suggest its potential for food supplementation to prevent obesity and related metabolic abnormalities.
Effect of Long-Term Dietary Arginyl-Fructose (AF) on Hyperglycemia and HbA1c in Diabetic db/db Mice
Authors: Lee Kwang-Hyoung , Ha Kyoung-Soo , Jo Sung-Hoon , Lee Chong , Kim Young-Cheul , Chung Kwang-Hoe , Kwon Young-In
Published: May 2014

We have previously reported that Amadori compounds exert anti-diabetic effects by lowering sucrose-induced hyperglycemia in normal Sprague-Dawley rats. In the present study we extended our recent findings to evaluate whether α-glucosidase inhibitor arginyl-fructose (AF) lowers blood glucose level in diabetic db/db mice, a genetic model for type 2 diabetes. The db/db mice were randomly assigned to high-carbohydrate diets (66.1% corn starch) with and without AF (4% in the diet) for 6 weeks. Changes in body weight, blood glucose level, and food intake were measured daily for 42 days. Dietary supplementation of AF resulted in a significant decrease of blood glucose level (p < 0.001) and body weight (p < 0.001). The level of HbA1c, a better indicator of plasma glucose concentration over prolonged periods of time, was also significantly decreased for 6-week period (p < 0.001). Dietary treatment of acarbose® (0.04% in diet), a positive control, also significantly alleviated the level of blood glucose, HbA1c, and body weight. These results indicate that AF Maillard reaction product improves postprandial hyperglycemia by suppressing glucose absorption as well as decreasing HbA1c level.
In Vitro Antiprotozoal Activity of Abietane Diterpenoids Isolated from Plectranthus barbatus Andr.
Authors: Mothana Ramzi , Al-Said Mansour , Al-Musayeib Nawal , Gamal Ali , Al-Massarani Shaza , Al-Rehaily Adnan , Abdulkader Majed , Maes Louis
Published: May 2014

Chromatographic separation of the n-hexane extract of the aerial part of Plectranthus barbatus led to the isolation of five abietane-type diterpenes: dehydroabietane (1); 5,6-didehydro-7-hydroxy-taxodone (2); taxodione (3); 20-deoxocarnosol (4) and 6α,11,12,-trihydroxy-7β,20-epoxy-8,11,13-abietatriene (5). The structures were determined using spectroscopic methods including one- and two-dimensional NMR methods. Compounds (1)–(3) and (5) are isolated here for the first time from the genus Plectranthus. The isolated abietane-type diterpenes tested in vitro for their antiprotozoal activity against erythrocytic schizonts of Plasmodium falciparum, intracellular amastigotes of Leishmania infantum and Trypanosoma cruzi and free trypomastigotes of T. brucei. Cytotoxicity was determined against fibroblast cell line MRC-5. Compound (2) 5,6-didehydro-7-hydroxy-taxodone showed remarkable activity with acceptable selectivity against P. falciparum (IC50 9.2 µM, SI 10.4) and T. brucei (IC50 1.9 µM, SI 50.5). Compounds (3)–(5) exhibited non-specific antiprotozoal activity due to high cytotoxicity. Compound (1) dehydroabietane showed no antiprotozoal potential.
IF-WS2/Nanostructured Carbon Hybrids Generation and Their Characterization
Authors: Luhrs Claudia , Moberg Michael , Maxson Ashley , Brewer Luke , Menon Sarath
Published: May 2014

With the aim to develop a new generation of materials that combine either the known energy absorbing properties of carbon nanofibers (CNF), or the carbon-carbon bond strength of graphene sheets (G), with the shock resistance properties reported for Inorganic Fullerene type WS2 structures (IF-WS2), hybrid CNF/IF-WS2 and G/IF-WS2 were generated, characterized and tested. Experimentation revealed that in situ growth of carbon nanostructures with inorganic fullerene tungsten disulfide particulates had to be performed from particular precursors and fabrication conditions to avoid undesirable byproducts that hinder fiber growth or deter graphene generation. The novel protocols that allowed us to integrate the IF-WS2 with the carbon nanostructures, producing dispersions at the nanoscale, are reported. Resulting hybrid CNF/IF-WS2 and G/IF-WS2 products were analyzed by X-ray Diffraction (XRD), Scanning Electron Microscope (SEM) and TEM (Transmission Electron Microscopy). The thermal stability of samples in air was evaluated by Thermogravimetric Analysis (TGA). CNF/IF-WS2 and G/IF-WS2 hybrids were introduced into epoxy matrices, and the mechanical properties of the resulting composites were analyzed using nanoindentation. Epoxy composite samples showed drastic improvements in the Young’s modulus and hardness values by the use of only 1% hybrid weight loadings. The carbon nanofiber inclusions seem to have a much greater impact on the mechanical properties of the composite than the graphene based counterparts.
Genetic Testing in the Diagnosis of Primary Ciliary Dyskinesia: State-of-the-Art and Future Perspectives
Authors: Collins Samuel , Walker Woolf , Lucas Jane
Published: May 2014

Primary ciliary dyskinesia (PCD) is a heterogeneous autosomal recessive condition affecting around 1:15,000. In people with PCD, microscopic motile cilia do not move normally resulting in impaired clearance of mucus and debris leading to repeated sinopulmonary infection. If diagnosis is delayed, permanent bronchiectasis and deterioration of lung function occurs. Other complications associated with PCD include congenital heart disease, hearing impairment and infertility. A small number of longitudinal studies suggest that lung function deteriorates before diagnosis of PCD but may stabilise following diagnosis with subsequent specialist management. Early diagnosis is therefore essential, but for a number of reasons referral for diagnostic testing is often delayed until older childhood or even adulthood. Functional diagnostic tests for PCD are expensive, time consuming and require specialist equipment and scientists. In the last few years, there have been considerable developments to identify genes associated with PCD, currently enabling 65% of patients to be identified by bi-allelic mutations. The rapid identification of new genes continues. This review will consider the evidence that early diagnosis of PCD is beneficial. It will review the recent advances in identification of PCD-associated genes and will discuss the role of genetic testing in PCD. It will then consider whether screening for PCD antenatally or in the new born is likely to become a feasible and acceptable for this rare disease.
Prenatal Screening Using Maternal Markers
Authors: Cuckle Howard
Published: May 2014

Maternal markers are widely used to screen for fetal neural tube defects (NTDs), chromosomal abnormalities and cardiac defects. Some are beginning to broaden prenatal screening to include pregnancy complications such as pre-eclampsia. The methods initially developed for NTDs using a single marker have since been built upon to develop high performance multi-maker tests for chromosomal abnormalities. Although cell-free DNA testing is still too expensive to be considered for routine application in public health settings, it can be cost-effective when used in combination with existing multi-maker marker tests. The established screening methods can be readily applied in the first trimester to identify pregnancies at high risk of pre-eclampsia and offer prevention though aspirin treatment. Prenatal screening for fragile X syndrome might be adopted more widely if the test was to be framed as a form of maternal marker screening.
Knowledge, Attitudes and Referral Patterns of Lynch Syndrome: A Survey of Clinicians in Australia
Authors: Tan Yen , Spurdle Amanda , Obermair Andreas
Published: May 2014

This study assessed Australian clinicians’ knowledge, attitudes and referral patterns of patients with suspected Lynch syndrome for genetic services. A total of 144 oncologists, surgeons, gynaecologists, general practitioners and gastroenterologists from the Australian Medical Association and Clinical Oncology Society responded to a web-based survey. Most respondents demonstrated suboptimal knowledge of Lynch syndrome. Male general practitioners who have been practicing for ≥10 years were less likely to offer genetic referral than specialists, and many clinicians did not recognize that immunohistochemistry testing is not a germline test. Half of all general practitioners did not actually refer patients in the past 12 months, and 30% of them did not feel that their role is to identify patients for genetic referral. The majority of clinicians considered everyone to be responsible for making the initial referral to genetic services, but a small preference was given to oncologists (15%) and general practitioners (13%). Patient information brochures, continuing genetic education programs and referral guidelines were favoured as support for practice. Targeted education interventions should be considered to improve referral. An online family history assessment tool with built-in decision support would be helpful in triaging high-risk individuals for pathology analysis and/or genetic assessment in general practice.
Benzo[b]thiophene-2-carbaldehyde
Authors: Mancuso Raffaella , Gabriele Bartolo
Published: May 2014

A novel expedient synthesis of benzo[b]thiophene-2-carbaldehyde 2 is reported. It is based on the one-pot sequential reaction of methylthiobenzene 1 with BuLi and DMF to give 2 in 80% isolated yield.
Biosynthetic Modularity Rules in the Bisintercalator Family of Antitumor Compounds
Authors: Fernández Javier , Marín Laura , Álvarez-Alonso Raquel , Redondo Saúl , Carvajal Juan , Villamizar Germán , Villar Claudio , Lombó Felipe
Published: May 2014

Diverse actinomycetes produce a family of structurally and biosynthetically related non-ribosomal peptide compounds which belong to the chromodepsipeptide family. These compounds act as bisintercalators into the DNA helix. They give rise to antitumor, antiparasitic, antibacterial and antiviral bioactivities. These compounds show a high degree of conserved modularity (chromophores, number and type of amino acids). This modularity and their high sequence similarities at the genetic level imply a common biosynthetic origin for these pathways. Here, we describe insights about rules governing this modular biosynthesis, taking advantage of the fact that nowadays five of these gene clusters have been made public (thiocoraline, triostin, SW-163 and echinomycin/quinomycin). This modularity has potential application for designing and producing novel genetic engineered derivatives, as well as for developing new chemical synthesis strategies. These would facilitate their clinical development.
Cephalopod Ink: Production, Chemistry, Functions and Applications
Authors: Derby Charles
Published: May 2014

One of the most distinctive and defining features of coleoid cephalopods—squid, cuttlefish and octopus—is their inking behavior. Their ink, which is blackened by melanin, but also contains other constituents, has been used by humans in various ways for millennia. This review summarizes our current knowledge of cephalopod ink. Topics include: (1) the production of ink, including the functional organization of the ink sac and funnel organ that produce it; (2) the chemical components of ink, with a focus on the best known of these—melanin and the biochemical pathways involved in its production; (3) the neuroecology of the use of ink in predator-prey interactions by cephalopods in their natural environment; and (4) the use of cephalopod ink by humans, including in the development of drugs for biomedical applications and other chemicals for industrial and other commercial applications. As is hopefully evident from this review, much is known about cephalopod ink and inking, yet more striking is how little we know. Towards closing that gap, future directions in research on cephalopod inking are suggested.
Overexpression and Characterization of a Novel Thermostable β-Agarase YM01-3, from Marine Bacterium Catenovulum agarivorans YM01T
Authors: Cui Fangyuan , Dong Sujie , Shi Xiaochong , Zhao Xia , Zhang Xiao-Hua
Published: May 2014

Genome sequencing of Catenovulum agarivorans YM01T reveals 15 open-reading frames (ORFs) encoding various agarases. In this study, extracellular proteins of YM01T were precipitated by ammonium sulfate and separated by one-dimensional gel electrophoresis. The results of in-gel agarase activity assay and mass spectrometry analysis revealed that the protein, YM01-3, was an agarase with the most evident agarolytic activity. Agarase YM01-3, encoded by the YM01-3 gene, consisted of 420 amino acids with a calculated molecular mass of 46.9 kDa and contained a glycoside hydrolase family 16 β-agarase module followed by a RICIN superfamily in the C-terminal region. The YM01-3 gene was cloned and expressed in Escherichia coli. The recombinant agarase, YM01-3, showed optimum activity at pH 6.0 and 60 °C and had a Km of 3.78 mg mL−1 for agarose and a Vmax of 1.14 × 104 U mg−1. YM01-3 hydrolyzed the β-1,4-glycosidic linkages of agarose, yielding neoagarotetraose and neoagarohexaose as the main products. Notably, YM01-3 was stable below 50 °C and retained 13% activity after incubation at 80 °C for 1 h, characteristics much different from other agarases. The present study highlights a thermostable agarase with great potential application value in industrial production.
Actinomycetes from Red Sea Sponges: Sources for Chemical and Phylogenetic Diversity
Authors: Abdelmohsen Usama , Yang Chen , Horn Hannes , Hajjar Dina , Ravasi Timothy , Hentschel Ute
Published: May 2014

The diversity of actinomycetes associated with marine sponges collected off Fsar Reef (Saudi Arabia) was investigated in the present study. Forty-seven actinomycetes were cultivated and phylogenetically identified based on 16S rRNA gene sequencing and were assigned to 10 different actinomycete genera. Eight putatively novel species belonging to genera Kocuria, Mycobacterium, Nocardia, and Rhodococcus were identified based on sequence similarity values below 98.2% to other 16S rRNA gene sequences available in the NCBI database. PCR-based screening for biosynthetic genes including type I and type II polyketide synthases (PKS-I, PKS-II) as well as nonribosomal peptide synthetases (NRPS) showed that 20 actinomycete isolates encoded each at least one type of biosynthetic gene. The organic extracts of nine isolates displayed bioactivity against at least one of the test pathogens, which were Gram-positive and Gram-negative bacteria, fungi, human parasites, as well as in a West Nile Virus protease enzymatic assay. These results emphasize that marine sponges are a prolific resource for novel bioactive actinomycetes with potential for drug discovery.
Marine Compound Catunaregin Inhibits Angiogenesis through the Modulation of Phosphorylation of Akt and eNOS in vivo and in vitro
Authors: Liu Jun-Xiu , Luo Min-Qi , Xia Meng , Wu Qi , Long Si-Mei , Hu Yaohua , Gao Guang-Chun , Yao Xiao-Li , He Mian , Su Huanxing , Luo Xiong-Ming , Yao Shu-Zhong
Published: May 2014

Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs) and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways.
Short-Term Intra-Subject Variation in Exhaled Volatile Organic Compounds (VOCs) in COPD Patients and Healthy Controls and Its Effect on Disease Classification
Authors: Phillips Christopher , Mac Parthaláin Neil , Syed Yasir , Deganello Davide , Claypole Timothy , Lewis Keir
Published: May 2014

Exhaled volatile organic compounds (VOCs) are of interest for their potential to diagnose disease non-invasively. However, most breath VOC studies have analyzed single breath samples from an individual and assumed them to be wholly consistent representative of the person. This provided the motivation for an investigation of the variability of breath profiles when three breath samples are taken over a short time period (two minute intervals between samples) for 118 stable patients with Chronic Obstructive Pulmonary Disease (COPD) and 63 healthy controls and analyzed by gas chromatography and mass spectroscopy (GC/MS). The extent of the variation in VOC levels differed between COPD and healthy subjects and the patterns of variation differed for isoprene versus the bulk of other VOCs. In addition, machine learning approaches were applied to the breath data to establish whether these samples differed in their ability to discriminate COPD from healthy states and whether aggregation of multiple samples, into single data sets, could offer improved discrimination. The three breath samples gave similar classification accuracy to one another when evaluated separately (66.5% to 68.3% subjects classified correctly depending on the breath repetition used). Combining multiple breath samples into single data sets gave better discrimination (73.4% subjects classified correctly). Although accuracy is not sufficient for COPD diagnosis in a clinical setting, enhanced sampling and analysis may improve accuracy further. Variability in samples, and short-term effects of practice or exertion, need to be considered in any breath testing program to improve reliability and optimize discrimination.
MALDI Mass Spectrometry Imaging for Visualizing In Situ Metabolism of Endogenous Metabolites and Dietary Phytochemicals
Authors: Fujimura Yoshinori , Miura Daisuke
Published: May 2014

Understanding the spatial distribution of bioactive small molecules is indispensable for elucidating their biological or pharmaceutical roles. Mass spectrometry imaging (MSI) enables determination of the distribution of ionizable molecules present in tissue sections of whole-body or single heterogeneous organ samples by direct ionization and detection. This emerging technique is now widely used for in situ label-free molecular imaging of endogenous or exogenous small molecules. MSI allows the simultaneous visualization of many types of molecules including a parent molecule and its metabolites. Thus, MSI has received much attention as a potential tool for pathological analysis, understanding pharmaceutical mechanisms, and biomarker discovery. On the other hand, several issues regarding the technical limitations of MSI are as of yet still unresolved. In this review, we describe the capabilities of the latest matrix-assisted laser desorption/ionization (MALDI)-MSI technology for visualizing in situ metabolism of endogenous metabolites or dietary phytochemicals (food factors), and also discuss the technical problems and new challenges, including MALDI matrix selection and metabolite identification, that need to be addressed for effective and widespread application of MSI in the diverse fields of biological, biomedical, and nutraceutical (food functionality) research.
Antinociceptive and Anti-Inflammatory Activities of the Sesame Oil and Sesamin
Authors: Monteiro Érika , Chibli Lucas , Yamamoto Célia , Pereira Mônica , Vilela Fernanda , Rodarte Mírian , De Oliveira Pinto Míriam , Da Penha Henriques do Amaral Maria , Silvério Marcelo , De Matos Araújo Ana , Da Luz André de Araújo Aílson , Del-Vechio-Vieira Glauciemar , De Sousa Orlando
Published: May 2014

Sesame oil is widely consumed as nutritious food, cooking oil, and in pharmaceuticals and food. In this study, the antinociceptive and anti-inflammatory properties of the sesame oil and sesamin were investigated. The sesame oil and sesamin reduced the number of abdominal contortions at the doses 100, 200, or 400 mg/kg. The first and second phases of the time paw licking were inhibited by sesame oil and sesamin (100, 200, or 400 mg/kg). After 90 min of treatment, sesame oil and sesamin increased the reaction time on a hot plate (200 or 400 mg/kg). Considering the tail-immersion assay, the sesame oil and sesamin produced significant effect after 60 min at the doses of 100, 200, or 400 mg/kg. After 4 h of application of the carrageenan, the sesame oil and sesamin were effective against the paw edema. The exudate volume and leucocyte migration were also reduced by sesame oil and sesamin. These results suggest that sesamin is one of the active compounds found in sesame oil and justify the antinociceptive and anti-inflammatory properties of this product.
Transcriptional Profiling of a Cross-Protective Salmonella enterica serovar Typhimurium UK-1 dam Mutant Identifies a Set of Genes More Transcriptionally Active Compared to Wild-Type, and Stably Transcribed across Biologically Relevant Microenvironments
Authors: Miller Claire , Pierlé Sebastian , Brayton Kelly , Ochoa Jennine , Shah Devendra , Lahmers Kevin
Published: May 2014

Vaccination with Salmonella enterica serovar Typhimurium lacking DNA adenine methyltransferase confers cross-protective immunity against multiple Salmonella serotypes. The mechanistic basis is thought to be associated with the de-repression of genes that are tightly regulated when transiting from one microenvironment to another. This de-repression provides a potential means for the production of a more highly expressed and stable antigenic repertoire capable of inducing cross-protective immune responses. To identify genes encoding proteins that may contribute to cross-protective immunity, we used a Salmonella Typhimurium DNA adenine methyltransferase mutant strain (UK-1 dam mutant) derived from the parental UK-1 strain, and assessed the transcriptional profile of the UK-1 dam mutant and UK-1 strain grown under conditions that simulate the intestinal or endosomal microenvironments encountered during the infective process. As expected, the transcriptional profile of the UK-1 dam mutant identified a set of genes more transcriptionally active when compared directly to UK-1, and stably transcribed in biologically relevant culture conditions. Further, 22% of these genes were more highly transcribed in comparison to two other clinically-relevant Salmonella serovars. The strategy employed here helps to identify potentially conserved proteins produced by the UK-1 dam mutant that stimulate and/or modulate the development of cross-protective immune responses toward multiple Salmonella serotypes.
Optimization of Biopolymer Based Transdermal Films of Metoclopramide as an Alternative Delivery Approach
Authors: Aktar Betül , Erdal Meryem , Sagirli Olcay , Güngör Sevgi , Özsoy Yıldız
Published: May 2014

The objectives of this study were to develop and to characterize sodium alginate based matrix-type transdermal films of metoclopramide hydrochloride (MTC) in order to improve patient compliance to treatment. The suitability of sodium alginate was shown to be a natural film former in terms of the physicochemical, mechanical, and bioadhesive features of the MTC loaded transdermal films. Terpinolene provided the highest drug release among the different terpenes (nerolidol, eucalyptol, dl-limonene, or terpinolene) assessed as enhancer. Attenuated Total Reflectance Infrared (ATR-FTIR) spectroscopy analysis performed to evaluate the effect of the transdermal films on skin barrier confirmed enhancer induced lipid bilayer disruption in stratum corneum, indicating its permeation enhancement effect.