bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances in Non-Viral DNA Vectors for Gene Therapy
Authors: Hardee Cinnamon , Arévalo-Soliz Lirio , Hornstein Benjamin , Zechiedrich Lynn
Published: February 2017

Uses of viral vectors have thus far eclipsed uses of non-viral vectors for gene therapy delivery in the clinic. Viral vectors, however, have certain issues involving genome integration, the inability to be delivered repeatedly, and possible host rejection. Fortunately, development of non-viral DNA vectors has progressed steadily, especially in plasmid vector length reduction, now allowing these tools to fill in specifically where viral or other non-viral vectors may not be the best options. In this review, we examine the improvements made to non-viral DNA gene therapy vectors, highlight opportunities for their further development, address therapeutic needs for which their use is the logical choice, and discuss their future expansion into the clinic
Estimating the Effect of Urban Growth on Annual Runoff Volume Using GIS in the Erbil Sub-Basin of the Kurdistan Region of Iraq
Authors: Hameed Hasan
Published: February 2017

The growth and spread of impervious surfaces within urbanizing catchment areas pose signiificant threats to the quality of natural and built-up environments. Impervious surfaces prevent water infiltration into the soil, resulting in increased runoff generation. The Erbil Sub-basin was selected because the impervious cover is increasing rapidly and is affecting the hydrological condition of the watershed. The overall aim of this study is to examine the impact of urban growth and other changes in land use on runoff response during the study period of 1984 to 2014. The study describes long-term hydrologic responses within the rapidly developing catchment area of Erbil city, in the Kurdistan Region of Iraq. Data from six rainfall stations in and around the Erbil Sub-basin were used. A Digital Elevation Model (DEM) was also used to extract the distribution of the drainage network. Historical levels of urban growth and the corresponding impervious areas, as well as land use/land cover changes were mapped from 1984 to 2014 using a temporal satellite image (Landsat) to determine land use/land cover changes. Land use/land cover was combined with a hydrological model (SCS-CN) to estimate the volume of runoff from the watershed. The study indicates that the urbanization of the watershed has increased the impervious land cover by 71% for the period from 1984 to 2004 and by 51% from 2004 to 2014. The volume of runoff was 85% higher in 2014 as compared to 1984 due to the increase in the impervious surface area; this is attributed to urban growth. The study also points out that the slope of the watershed in the Erbil sub-basin should be taken into account in surface runoff estimation as the upstream part of the watershed has a high gradient and the land is almost barren with very little vegetation cover; this causes an increase in the velocity of the flow and increases the risk of flooding in Erbil city.
Temporal Trends in Satellite-Derived Erythemal UVB and Implications for Ambient Sun Exposure Assessment
Authors: Langston Marvin , Dennis Leslie , Lynch Charles , Roe Denise , Brown Heidi
Published: February 2017

Ultraviolet radiation (UVR) has been associated with various health outcomes, including skin cancers, vitamin D insufficiency, and multiple sclerosis. Measurement of UVR has been difficult, traditionally relying on subject recall. We investigated trends in satellite-derived UVB from 1978 to 2014 within the continental United States (US) to inform UVR exposure assessment and determine the potential magnitude of misclassification bias created by ignoring these trends. Monthly UVB data remotely sensed from various NASA satellites were used to investigate changes over time in the United States using linear regression with a harmonic function. Linear regression models for local geographic areas were used to make inferences across the entire study area using a global field significance test. Temporal trends were investigated across all years and separately for each satellite type due to documented differences in UVB estimation. UVB increased from 1978 to 2014 in 48% of local tests. The largest UVB increase was found in Western Nevada (0.145 kJ/m2 per five-year increment), a total 30-year increase of 0.87 kJ/m2. This largest change only represented 17% of total ambient exposure for an average January and 2% of an average July in Western Nevada. The observed trends represent cumulative UVB changes of less than a month, which are not relevant when attempting to estimate human exposure. The observation of small trends should be interpreted with caution due to measurement of satellite parameter inputs (ozone and climatological factors) that may impact derived satellite UVR nearly 20% compared to ground level sources. If the observed trends hold, satellite-derived UVB data may reasonably estimate ambient UVB exposures even for outcomes with long latency phases that predate the satellite record.
The Impact of Heat Exposure and Sleep Restriction on Firefighters’ Work Performance and Physiology during Simulated Wildfire Suppression
Authors: Vincent Grace , Aisbett Brad , Larsen Brianna , Ridgers Nicola , Snow Rod , Ferguson Sally
Published: February 2017

This study was designed to examine the effects of ambient heat on firefighters’ physical task performance, and physiological and perceptual responses when sleep restricted during simulated wildfire conditions. Thirty firefighters were randomly allocated to the sleep restricted (n = 17, SR; 19 °C, 4-h sleep opportunity) or hot and sleep restricted (n = 13, HOT + SR; 33 °C, 4-h sleep opportunity) condition. Firefighters performed two days of simulated, intermittent, self-paced work circuits comprising six firefighting tasks. Heart rate, and core temperature were measured continuously. After each task, firefighters reported their rating of perceived exertion and thermal sensation. Effort sensation was also reported after each work circuit. Fluids were consumed ad libitum. Urine volume and urine specific gravity were analysed. Sleep was monitored using polysomnography. There were no differences between the SR and HOT + SR groups in firefighters’ physiological responses, hydration status, ratings of perceived exertion, motivation, and four of the six firefighting tasks (charged hose advance, rake, hose rolling, static hose hold). Black out hose and lateral repositioning were adversely affected in the HOT + SR group. Working in hot conditions did not appear to consistently impair firefighters work performance, physiology, and perceptual responses. Future research should determine whether such findings remain true when individual tasks are performed over longer durations.
Family Environment and Childhood Obesity: A New Framework with Structural Equation Modeling
Authors: Huang Hui , Wan Mohamed Radzi Che , Salarzadeh Jenatabadi Hashem
Published: February 2017

The main purpose of the current article is to introduce a framework of the complexity of childhood obesity based on the family environment. A conceptual model that quantifies the relationships and interactions among parental socioeconomic status, family food security level, child’s food intake and certain aspects of parental feeding behaviour is presented using the structural equation modeling (SEM) concept. Structural models are analysed in terms of the direct and indirect connections among latent and measurement variables that lead to the child weight indicator. To illustrate the accuracy, fit, reliability and validity of the introduced framework, real data collected from 630 families from Urumqi (Xinjiang, China) were considered. The framework includes two categories of data comprising the normal body mass index (BMI) range and obesity data. The comparison analysis between two models provides some evidence that in obesity modeling, obesity data must be extracted from the dataset and analysis must be done separately from the normal BMI range. This study may be helpful for researchers interested in childhood obesity modeling based on family environment.
Perceptions of Improved Biomass and Liquefied Petroleum Gas Stoves in Puno, Peru: Implications for Promoting Sustained and Exclusive Adoption of Clean Cooking Technologies
Authors: Hollada Jacqueline , Williams Kendra , Miele Catherine , Danz David , Harvey Steven , Checkley William
Published: February 2017

Many households in low- and middle-income countries cook with inefficient biomass-burning stoves, which cause high levels of household air pollution and threaten long-term health. Although clean stoves and fuels are available, uptake and consistent use has been low. Using observations and in-depth interviews, we assessed the attitudes, preferences, and beliefs about traditional versus liquefied petroleum gas (LPG) stoves in rural Puno, Peru. A total of 31 in-depth interviews were conducted with primary cooks and their families, health workers, community leaders, and improved stove contractors. Six in-home observations of meal preparation were also conducted. Six major barriers to consistent use of clean stoves were identified: (1) perceived differences in food taste and nutrition by stove type; (2) cooking niches filled by different stoves; (3) social norms related to cooking practices; (4) safety concerns; (5) comparative costs of using different stoves; and (6) lack of awareness and concern about long-term health risks. These findings suggest that to successfully reduce household air pollution, clean cooking programs and policies must consider the many factors influencing adoption beyond health, such as cost, taste, fears, and cultural traditions. These factors could be incorporated into community-based and national efforts to scale-up sustained and exclusive adoption of clean cooking.
Selecting Cooking Methods to Decrease Persistent Organic Pollutant Concentrations in Food of Animal Origin Using a Consensus Decision-Making Model
Authors: Tan Xiao , Gong Zaiwu , Huang Minji , Wang Zhou-Jing
Published: February 2017

Persistent organic pollutants (POPs) pose serious threats to human health. Increasing attention has been paid to POPs to protect the environment and prevent disease. Humans are exposed to POPs through diet (the major route), inhaling air and dust and skin contact. POPs are very lipophilic and hydrophobic, meaning that they accumulate in fatty tissues in animals and can biomagnify. Humans can therefore be exposed to relatively high POP concentrations in food of animal origin. Cooking animal products can decrease the POP contents, and different cooking methods achieve different reduction rates. Here, a consensus decision-making model with interval preference relations is used to prioritize cooking methods for specific animal products in terms of reducing POP concentrations. Two consistency mathematical expressions (I-consistency and I I -consistency) are defined, then the ideal interval preference relations are determined for the cooking methods with respect to different social choice principles. The objective is to minimize disparities between individual judgments and the ideal consensus judgment. Consistency is used as a constraint to determine the rationality of the consistency definitions. A numerical example indicated that baking is the best cooking method for decreasing POP concentrations in grass carp. The I-consistency results were more acceptable than the I I -consistency results.
Fine Particulate Matter Concentrations in Urban Chinese Cities, 2005–2016: A Systematic Review
Authors: He Mike , Zeng Xiange , Zhang Kaiyue , Kinney Patrick
Published: February 2017

Background: Particulate matter pollution has become a growing health concern over the past few decades globally. The problem is especially evident in China, where particulate matter levels prior to 2013 are publically unavailable. We conducted a systematic review of scientific literature that reported fine particulate matter (PM2.5) concentrations in different regions of China from 2005 to 2016. Methods: We searched for English articles in PubMed and Embase and for Chinese articles in the China National Knowledge Infrastructure (CNKI). We evaluated the studies overall and categorized the collected data into six geographical regions and three economic regions. Results: The mean (SD) PM2.5 concentration, weighted by the number of sampling days, was 60.64 (33.27) μg/m3 for all geographic regions and 71.99 (30.20) μg/m3 for all economic regions. A one-way ANOVA shows statistically significant differences in PM2.5 concentrations between the various geographic regions (F = 14.91, p < 0.0001) and the three economic regions (F = 4.55, p = 0.01). Conclusions: This review identifies quantifiable differences in fine particulate matter concentrations across regions of China. The highest levels of fine particulate matter were found in the northern and northwestern regions and especially Beijing. The high percentage of data points exceeding current federal regulation standards suggests that fine particulate matter pollution remains a huge problem for China. As pre-2013 emissions data remain largely unavailable, we hope that the data aggregated from this systematic review can be incorporated into current and future models for more accurate historical PM2.5 estimates.
Analysis of the Spatial Variation of Network-Constrained Phenomena Represented by a Link Attribute Using a Hierarchical Bayesian Model
Authors: Wang Zhensheng , Yue Yang , Li Qingquan , Nie Ke , Yu Changbin
Published: February 2017

The spatial variation of geographical phenomena is a classical problem in spatial data analysis and can provide insight into underlying processes. Traditional exploratory methods mostly depend on the planar distance assumption, but many spatial phenomena are constrained to a subset of Euclidean space. In this study, we apply a method based on a hierarchical Bayesian model to analyse the spatial variation of network-constrained phenomena represented by a link attribute in conjunction with two experiments based on a simplified hypothetical network and a complex road network in Shenzhen that includes 4212 urban facility points of interest (POIs) for leisure activities. Then, the methods named local indicators of network-constrained clusters (LINCS) are applied to explore local spatial patterns in the given network space. The proposed method is designed for phenomena that are represented by attribute values of network links and is capable of removing part of random variability resulting from small-sample estimation. The effects of spatial dependence and the base distribution are also considered in the proposed method, which could be applied in the fields of urban planning and safety research.
Identification and Characterization of Lipopolysaccharide Induced TNFα Factor from Blunt Snout Bream, Megalobrama amblycephala
Authors: Lv Yina , Xiang Xinying , Jiang Yuhong , Tang Leilei , Zhou Yi , Zhong Huan , Xiao Jun , Yan Jinpeng
Published: February 2017

Lipopolysaccharide induced TNFα factor (LITAF) is an important transcription factor responsible for regulation of tumor necrosis factor α. In this study, a novel litaf gene (designated as Malitaf) was identified and characterized from blunt snout bream, Megalobrama amblycephala. The full-length cDNA of Malitaf was of 956 bp, encoding a polypeptide of 161 amino acids with high similarity to other known LITAFs. A phylogenetic tree also showed that Malitaf significantly clustered with those of other teleost, indicating that Malitaf was a new member of fish LITAF family. The putative maLITAF protein possessed a highly conserved LITAF domain with two CXXC motifs. The mRNA transcripts of Malitaf were detected in all examined tissues of healthy M. amblycephala, including kidney, head kidney, muscle, liver, spleen, gill, and heart, and with the highest expression in immune organs: spleen and head kidney. The expression level of Malitaf in spleen was rapidly up-regulated and peaked (1.29-fold, p < 0.05) at 2 h after lipopolysaccharide (LPS) stimulation. Followed the stimulation of Malitaf, Matnfα transcriptional level was also transiently induced to a high level (51.74-fold, p < 0.001) at 4 h after LPS stimulation. Taken together, we have identified a putative fish LITAF ortholog, which was a constitutive and inducible immune response gene involved in M. amblycephala innate immunity during the course of a pathogenic infection.
Immunoinformatics Features Linked to Leishmania Vaccine Development: Data Integration of Experimental and In Silico Studies
Authors: Brito Rory , Guimarães Frederico , Velloso João , Corrêa-Oliveira Rodrigo , Ruiz Jeronimo , Reis Alexandre , Resende Daniela
Published: February 2017

Leishmaniasis is a wide-spectrum disease caused by parasites from Leishmania genus. There is no human vaccine available and it is considered by many studies as apotential effective tool for disease control. To discover novel antigens, computational programs have been used in reverse vaccinology strategies. In this work, we developed a validation antigen approach that integrates prediction of B and T cell epitopes, analysis of Protein-Protein Interaction (PPI) networks and metabolic pathways. We selected twenty candidate proteins from Leishmania tested in murine model, with experimental outcome published in the literature. The predictions for CD4+ and CD8+ T cell epitopes were correlated with protection in experimental outcomes. We also mapped immunogenic proteins on PPI networks in order to find Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with them. Our results suggest that non-protective antigens have lowest frequency of predicted T CD4+ and T CD8+ epitopes, compared with protective ones. T CD4+ and T CD8+ cells are more related to leishmaniasis protection in experimental outcomes than B cell predicted epitopes. Considering KEGG analysis, the proteins considered protective are connected to nodes with few pathways, including those associated with ribosome biosynthesis and purine metabolism.
n-Butylidenephthalide Regulated Tumor Stem Cell Genes EZH2/AXL and Reduced Its Migration and Invasion in Glioblastoma
Authors: Yen Ssu-Yin , Chuang Hong-Meng , Huang Mao-Hsuan , Lin Shinn-Zong , Chiou Tzyy-Wen , Harn Horng-Jyh
Published: February 2017

Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20–21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem cells (CSCs), which display radioresistant, chemoresistant, self-renewal and tumorigenic potential. Enhancers of Zeste 2 (EZH2) and AXL receptor tyrosine kinase (AXL) are both highly expressed in GBM. Additionally, they are an essential regulator involved in CSCs maintenance, migration, invasion, epithelial-to-mesenchymal transition (EMT), stemness, metastasis and patient survival. In this study, we used a small molecule, n-butylidenephthalide (BP), to assess the anti-GBM stem-like cells potential, and then tried to find out the associated genes involved with regulation in migration and invasion. We demonstrated that BP reduced the expression of AXL and stemness related genes in a dose-dependent manner. The migratory and invasive capabilities of GBM stem-like cells could be reduced by AXL/EZH2. Finally, in the overexpression of AXL, EZH2 and Sox2 by transfection in GBM stem-like cells, we found that AXL/EZH2/TGF-ꞵ1, but not Sox2, might be a key regulator in tumor invasion, migration and EMT. These results might help in the development of a new anticancer compound and can be a target for treating GBM.
Soy-Leaf Extract Exerts Atheroprotective Effects via Modulation of Krüppel-Like Factor 2 and Adhesion Molecules
Authors: Han Jong-Min , Li Hua , Cho Moon-Hee , Baek Seung-Hwa , Lee Chul-Ho , Park Ho-Yong , Jeong Tae-Sook
Published: February 2017

Soy-leaf extracts exert their cardioprotective effects by inducing endothelium-dependent vasodilation in the arteries, and they favorably modulate the serum lipid profile. In this study, we investigated the atheroprotective effects of an ethanol extract of soy leaf (ESL) in human umbilical vein endothelial cells (HUVECs) and high-cholesterol diet (HCD)-fed low-density lipoprotein receptor deficient (LDLR−/−) mice. ESL induced the expression of Krüppel-like factor 2 (KLF2), an endothelial transcription factor, and endothelial nitric oxide synthase (eNOS), and suppressed the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) through moderate inflammatory signal activation, not only in tumor necrosis factor-α (TNF-α)-stimulated HUVECs but also in 7-ketocholesterol (7-KC)-stimulated HUVECs. ESL supplementation reduced aortic lesion formation in Western diet-fed LDLR−/− mice by 46% (p < 0.01) compared to the HCD group. ESL also markedly decreased the aortic expression levels of VCAM-1, ICAM-1, monocyte chemotactic protein-1 (MCP-1), TNF-α, IL-6, IL-1β, matrix metallopeptidase 9 (MMP-9), and fractalkine, while the expression of KLF2 was significantly increased. These results suggest that ESL supplementation has potential for preventing HCD-induced atherosclerosis effectively.
The Role of the Neutrophil to Lymphocyte Ratio for Survival Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone
Authors: Boegemann Martin , Schlack Katrin , Thomes Stefan , Steinestel Julie , Rahbar Kambiz , Semjonow Axel , Schrader Andres , Aringer Martin , Krabbe Laura-Maria
Published: February 2017

The purpose of this study was to examine the prognostic capability of baseline neutrophil-to-lymphocyte-ratio (NLR) and NLR-change under Abiraterone in metastatic castration-resistant prostate cancer patients. The impact of baseline NLR and change after eight weeks of treatment on progression-free survival (PFS) and overall survival (OS) was analyzed using Kaplan-Meier-estimates and Cox-regression. 79 men with baseline NLR <5 and 17 with NLR >5 were analyzed. In baseline analysis of PFS NLR >5 was associated with non-significantly shorter median PFS (five versus 10 months) (HR: 1.6 (95%CI:0.9–2.8); p = 0.11). After multivariate adjustment (MVA), ECOG > 0–1, baseline LDH>upper limit of normal (UNL) and presence of visceral metastases were independent prognosticators. For OS, NLR >5 was associated with shorter survival (seven versus 19 months) (HR: 2.3 (95%CI:1.3–4.0); p < 0.01). In MVA, ECOG > 0–1 and baseline LDH > UNL remained independent prognosticators. After 8 weeks of Abiraterone NLR-change to <5 prognosticated worse PFS (five versus 12 months) (HR: 4.1 (95%CI:1.1–15.8); p = 0.04). MVA showed a trend towards worse PFS for NLR-change to <5 (p = 0.11). NLR-change to <5 led to non-significant shorter median OS (seven versus 16 months) (HR: 2.3 (95%CI:0.7–7.1); p = 0.15). MVA showed non-significant difference for OS. We concluded baseline NLR <5 is associated with improved survival. In contrast, in patients with baseline NLR >5, NLR-change to <5 after eight weeks of Abiraterone was associated with worse survival and should be interpreted carefully.
The Mechanisms and Biomedical Applications of an NIR BODIPY-Based Switchable Fluorescent Probe
Authors: Cheng Bingbing , Bandi Venugopal , Yu Shuai , D’Souza Francis , Nguyen Kytai , Hong Yi , Tang Liping , Yuan Baohong
Published: February 2017

Highly environment-sensitive fluorophores have been desired for many biomedical applications. Because of the noninvasive operation, high sensitivity, and high specificity to the microenvironment change, they can be used as excellent probes for fluorescence sensing/imaging, cell tracking/imaging, molecular imaging for cancer, and so on (i.e., polarity, viscosity, temperature, or pH measurement). In this work, investigations of the switching mechanism of a recently reported near-infrared environment-sensitive fluorophore, ADP(CA)2, were conducted. Besides, multiple potential biomedical applications of this switchable fluorescent probe have been demonstrated, including wash-free live-cell fluorescence imaging, in vivo tissue fluorescence imaging, temperature sensing, and ultrasound-switchable fluorescence (USF) imaging. The fluorescence of the ADP(CA)2 is extremely sensitive to the microenvironment, especially polarity and viscosity. Our investigations showed that the fluorescence of ADP(CA)2 can be switched on by low polarity, high viscosity, or the presence of protein and surfactants. In wash-free live-cell imaging, the fluorescence of ADP(CA)2 inside cells was found much brighter than the dye-containing medium and was retained for at least two days. In all of the fluorescence imaging applications conducted in this study, high target-to-noise (>5-fold) was achieved. In addition, a high temperature sensitivity (73-fold per Celsius degree) of ADP(CA)2-based temperature probes was found in temperature sensing.
Redox Proteomics and Platelet Activation: Understanding the Redox Proteome to Improve Platelet Quality for Transfusion
Authors: Sonego Giona , Abonnenc Mélanie , Tissot Jean-Daniel , Prudent Michel , Lion Niels
Published: February 2017

Blood banks use pathogen inactivation (PI) technologies to increase the safety of platelet concentrates (PCs). The characteristics of PI-treated PCs slightly differ from those of untreated PCs, but the underlying reasons are not well understood. One possible cause is the generation of oxidative stress during the PI process. This is of great interest since reactive oxygen species (ROS) act as second messengers in platelet functions. Furthermore, there are links between protein oxidation and phosphorylation, another mechanism that is critical for cell regulation. Current research efforts focus on understanding the underlying mechanisms and identifying new target proteins. Proteomics technologies represent powerful tools for investigating signaling pathways involving ROS and post-translational modifications such as phosphorylation, while quantitative techniques enable the comparison of the platelet resting state versus the stimulated state. In particular, redox cysteine is a key player in platelet activation upon stimulation by different agonists. This review highlights the experiments that have provided insights into the roles of ROS in platelet function and the implications for platelet transfusion, and potentially in diseases such as inflammation and platelet hyperactivity. The review also describes the implication of redox mechanism in platelet storage considerations.
Hazelnut (Corylus avellana L.) Shells Extract: Phenolic Composition, Antioxidant Effect and Cytotoxic Activity on Human Cancer Cell Lines
Authors: Esposito Tiziana , Sansone Francesca , Franceschelli Silvia , Del Gaudio Pasquale , Picerno Patrizia , Aquino Rita , Mencherini Teresa
Published: February 2017

Hazelnut shells, a by-product of the kernel industry processing, are reported to contain high amount of polyphenols. However, studies on the chemical composition and potential effects on human health are lacking. A methanol hazelnut shells extract was prepared and dried. Our investigation allowed the isolation and characterization of different classes of phenolic compounds, including neolignans, and a diarylheptanoid, which contribute to a high total polyphenol content (193.8 ± 3.6 mg of gallic acid equivalents (GAE)/g of extract). Neolignans, lawsonicin and cedrusin, a cyclic diarylheptanoid, carpinontriol B, and two phenol derivatives, C-veratroylglycol, and β-hydroxypropiovanillone, were the main components of the extract (0.71%–2.93%, w/w). The biological assays suggested that the extract could be useful as a functional ingredient in food technology and pharmaceutical industry showing an in vitro scavenging activity against the radical 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) (EC50 = 31.7 μg/mL with respect to α-tocopherol EC50 = 10.1 μg/mL), and an inhibitory effect on the growth of human cancer cell lines A375, SK-Mel-28 and HeLa (IC50 = 584, 459, and 526 μg/mL, respectively). The expression of cleaved forms of caspase-3 and poly(ADP-ribose) polymerase-1 (PARP-1) suggested that the extract induced apoptosis through caspase-3 activation in both human malignant melanoma (SK-Mel-28) and human cervical cancer (HeLa) cell lines. The cytotoxic activity relies on the presence of the neolignans (balanophonin), and phenol derivatives (gallic acid), showing a pro-apoptotic effect on the tested cell lines, and the neolignan, cedrusin, with a cytotoxic effect on A375 and HeLa cells.
Defense Responses in Grapevine (cv. Mourvèdre) after Inoculation with the Botryosphaeria Dieback Pathogens Neofusicoccum parvum and Diplodia seriata and Their Relationship with Flowering
Authors: Spagnolo Alessandro , Mondello Vincenzo , Larignon Philippe , Villaume Sandra , Rabenoelina Fanja , Clément Christophe , Fontaine Florence
Published: February 2017

As a result of the increasing economic impact of grapevine trunk diseases on viticulture worldwide, efficient and viable control strategies are urgently needed. However, understanding both plant-pathogen interactions and plant physiological changes related to these diseases is fundamental to such an achievement. In this study, we analyzed the effect of inoculation with the Botryosphaeria dieback fungal agents, Neofusicoccum parvum and Diplodia seriata, with and without inflorescence removal at the onset of G stage (separated clusters), I stage (flowering) and M stage (veraison). A measure of lesion size and real-time reverse-transcription polymerase chain reaction-based analysis were carried out. The results clearly show the importance of inflorescences in the development of lesions associated with Botryosphaeria dieback pathogens inoculated on green stems of adult vines, especially at the onset of flowering. At flowering, the biggest necroses were observed with the inflorescences present, as well as an activation of the studied defense responses. Thus, an ineffective response to the pathogen could be consistent with a possible metabolic reprogramming linked to the host phenophase.
Calcium Signaling in Interstitial Cells: Focus on Telocytes
Authors: Radu Beatrice , Banciu Adela , Banciu Daniel , Radu Mihai , Cretoiu Dragos , Cretoiu Sanda
Published: February 2017

In this review, we describe the current knowledge on calcium signaling pathways in interstitial cells with a special focus on interstitial cells of Cajal (ICCs), interstitial Cajal-like cells (ICLCs), and telocytes. In detail, we present the generation of Ca2+ oscillations, the inositol triphosphate (IP3)/Ca2+ signaling pathway and modulation exerted by cytokines and vasoactive agents on calcium signaling in interstitial cells. We discuss the physiology and alterations of calcium signaling in interstitial cells, and in particular in telocytes. We describe the physiological contribution of calcium signaling in interstitial cells to the pacemaking activity (e.g., intestinal, urinary, uterine or vascular pacemaking activity) and to the reproductive function. We also present the pathological contribution of calcium signaling in interstitial cells to the aortic valve calcification or intestinal inflammation. Moreover, we summarize the current knowledge of the role played by calcium signaling in telocytes in the uterine, cardiac and urinary physiology, and also in various pathologies, including immune response, uterine and cardiac pathologies.
A Conjugate Based on Anti-HER2 Diaffibody and Auristatin E Targets HER2-Positive Cancer Cells
Authors: Serwotka-Suszczak Anna , Sochaj-Gregorczyk Alicja , Pieczykolan Jerzy , Krowarsch Daniel , Jelen Filip , Otlewski Jacek
Published: February 2017

Antibody-drug conjugates (ADCs) have recently emerged as efficient and selective cancer treatment therapeutics. Currently, alternative forms of drug carriers that can replace monoclonal antibodies are under intensive investigation. Here, a cytotoxic conjugate of an anti-HER2 (Human Epidermal Growth Factor Receptor 2) diaffibody with monomethyl-auristatin E (MMAE) is proposed as a potential anticancer therapeutic. The anti-HER2 diaffibody was based on the ZHER2:4 affibody amino acid sequence. The anti-HER2 diaffibody has been expressed as a His-tagged protein in E. coli and purified by Ni-nitrilotriacetyl (Ni-NTA) agarose chromatography. The molecule was properly folded, and the high affinity and specificity of its interaction with HER2 was confirmed by surface plasmon resonance (SPR) and flow cytometry, respectively. The (ZHER2:4)2DCS-MMAE conjugate was obtained by coupling the maleimide group linked with MMAE to cysteines, which were introduced in a drug conjugation sequence (DCS). Cytotoxicity of the conjugate was evaluated using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide MTT assay and the xCELLigence Real-Time Cell Analyzer. Our experiments demonstrated that the conjugate delivered auristatin E specifically to HER2-positive tumor cells, which finally led to their death. These results indicate that the cytotoxic diaffibody conjugate is a highly potent molecule for the treatment of various types of cancer overexpressing HER2 receptors.
An In Silico Identification of Common Putative Vaccine Candidates against Treponema pallidum: A Reverse Vaccinology and Subtractive Genomics Based Approach
Authors: Kumar Jaiswal Arun , Tiwari Sandeep , Jamal Syed , Barh Debmalya , Azevedo Vasco , Soares Siomar
Published: February 2017

Sexually transmitted infections (STIs) are caused by a wide variety of bacteria, viruses, and parasites that are transmitted from one person to another primarily by vaginal, anal, or oral sexual contact. Syphilis is a serious disease caused by a sexually transmitted infection. Syphilis is caused by the bacterium Treponema pallidum subspecies pallidum. Treponema pallidum (T. pallidum) is a motile, gram-negative spirochete, which can be transmitted both sexually and from mother to child, and can invade virtually any organ or structure in the human body. The current worldwide prevalence of syphilis emphasizes the need for continued preventive measures and strategies. Unfortunately, effective measures are limited. In this study, we focus on the identification of vaccine targets and putative drugs against syphilis disease using reverse vaccinology and subtractive genomics. We compared 13 strains of T. pallidum using T. pallidum Nichols as the reference genome. Using an in silicoapproach, four pathogenic islands were detected in the genome of T. pallidum Nichols. We identified 15 putative antigenic proteins and sixdrug targets through reverse vaccinology and subtractive genomics, respectively, which can be used as candidate therapeutic targets in the future.
Use of Mature miRNA Strand Selection in miRNAs Families in Cervical Cancer Development
Authors: Granados-López Angelica , Ruiz-Carrillo José , Servín-González Luis , Martínez-Rodríguez José , Reyes-Estrada Claudia , Gutiérrez-Hernández Rosalinda , López Jesús
Published: February 2017

Aberrant miRNA expression is well recognized as a cancer hallmark, nevertheless miRNA function and expression does not always correlate in patients tissues and cell lines studies. In addition to this issue, miRNA strand usage conduces to increased cell signaling pathways modulation diversifying cellular processes regulation. In cervical cancer, 20 miRNA families are involved in carcinogenesis induction and development to this moment. These families have 5p and 3p strands with different nucleotide (nt) chain sizes. In general, mature 5p strands are larger: two miRNAs of 24 nt, 24 miRNAs of 23 nt, 35 miRNAs of 22 nt and three miRNAs of 21 nt. On the other hand, the 3p strands lengths observed are: seven miRNAs of 23 nt, 50 miRNAs of 22 nt, six miRNAs of 21 nt and four miRNAs of 20 nt. Based on the analysis of the 20 miRNA families associated with cervical cancer, 67 3p strands and 65 5p strands are selected suggesting selectivity and specificity mechanisms regulating cell processes like proliferation, apoptosis, migration, invasion, metabolism and Warburg effect. The insight reviewed here could be used in the miRNA based therapy, diagnosis and prognosis approaches.
Evaluation of Not-Activated and Activated PRP in Hair Loss Treatment: Role of Growth Factor and Cytokine Concentrations Obtained by Different Collection Systems
Authors: Gentile Pietro , Cole John , Cole Megan , Garcovich Simone , Bielli Alessandra , Scioli Maria , Orlandi Augusto , Insalaco Chiara , Cervelli Valerio
Published: February 2017

Platelet rich plasma (PRP) was tested as a potential therapy for androgenetic alopecia (AGA) through two different clinical protocols in which one population (18 participants) received half-head treatment with autologous non-activated PRP (A-PRP) produced by CPunT Preparation System (Biomed Device, Modena, Italy) and the other half-head with placebo, and a second separated population in which all participants (n = 6, 3 participants per group) received treatment with calcium-activated PRP (AA-PRP) produced from one of two different PRP collection devices (Regen Blood Cell Therapy or Arthrex Angel System). For the A-PRP study, three treatments were administered over 30-day intervals. Trichoscan analysis of patients, three months post-treatment, showed a clinical improvement in the number of hairs in the target area (36 ± 3 hairs) and in total hair density (65± 5 hair cm2), whereas negligible improvements in hair count (1.1± 1.4 hairs) and density (1.9 ± 10.2 hair cm2) were seen in the region of the scalp that received placebo. Microscopic evaluation conducted two weeks after treatment showed also an increase in epidermal thickness, Ki67+ keratinocytes, and in the number of follicles. The AA-PRP treatment groups received a singular set of injections, and six months after the treatments were administered, notable differences in clinical outcomes were obtained from the two PRP collection devices (+90 ± 6 hair cm2 versus -73 ± 30 hair cm2 hair densities, Regen versus Arthrex). Growth factor concentrations in AA-PRP prepared from the two collection devices did not differ significantly upon calcium activation.
The Cell Death Triggered by the Nuclear Localized RxLR Effector PITG_22798 from Phytophthora infestans Is Suppressed by the Effector AVR3b
Authors: Wang Hongyang , Ren Yajuan , Zhou Jing , Du Juan , Hou Juan , Jiang Rui , Wang Haixia , Tian Zhendong , Xie Conghua
Published: February 2017

Phytopathogenic oomycetes, such as Phytophthora infestans, potentially secrete many RxLR effector proteins into plant cells to modulate plant immune responses and promote colonization. However, the molecular mechanisms by which these RxLR effectors suppress plant immune responses are largely unknown. Here we describe an RxLR effector PITG_22798 (Gene accession: XM_002998349) that was upregulated during early infection of potato by P. infestans. By employment of agroinfiltration, we observed that PITG_22798 triggers cell death in Nicotiana benthamiana. Confocal microscopic examination showed that PITG_22798-GFP (Green Fluorescent Protein) located in the host nucleus when expressed transiently in N. benthamiana leaves. A nuclear localization signal (NLS) domain of PITG_22798 is important for nuclear localization and cell death-inducing activity. Sequence alignment and transient expression showed that PITG_22798 from diverse P. infestans isolates are conserved, and transient expression of PITG_22798 enhances P. infestans colonization of N. benthamiana leaves, which suggests that PITG_22798 contributes to P. infestans infection. PITG_22798-triggered cell death is dependent on SGT1-mediated signaling and is suppressed by the P. infestans avirulence effector 3b (AVR3b). The present research provides a clue for further investigation of how P. infestans effector PITG_22798 associates with and modulates host immunity.
Role of Splice Variants of Gtf2i, a Transcription Factor Localizing at Postsynaptic Sites, and Its Relation to Neuropsychiatric Diseases
Authors: Shirai Yoshinori , Li Weidong , Suzuki Tatsuo
Published: February 2017

We previously reported that various mRNAs were associated with postsynaptic density (PSD) purified from rat forebrain. Among the thousands of PSD-associated mRNAs, we highlight the biology of the general transcription factor II-I (Gtf2i) mRNA, focusing on the significance of its versatile splicing for targeting its own mRNA into dendrites, regulation of translation, and the effects of Gtf2i expression level as well as its relationship with neuropsychiatric disorders.
Big Data Analytics for Genomic Medicine
Authors: He Karen , Ge Dongliang , He Max
Published: February 2017

Genomic medicine attempts to build individualized strategies for diagnostic or therapeutic decision-making by utilizing patients’ genomic information. Big Data analytics uncovers hidden patterns, unknown correlations, and other insights through examining large-scale various data sets. While integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs) on a Big Data infrastructure exhibit challenges, they also provide a feasible opportunity to develop an efficient and effective approach to identify clinically actionable genetic variants for individualized diagnosis and therapy. In this paper, we review the challenges of manipulating large-scale next-generation sequencing (NGS) data and diverse clinical data derived from the EHRs for genomic medicine. We introduce possible solutions for different challenges in manipulating, managing, and analyzing genomic and clinical data to implement genomic medicine. Additionally, we also present a practical Big Data toolset for identifying clinically actionable genetic variants using high-throughput NGS data and EHRs.
Clinical and Molecular Evidence of ABCC11 Protein Expression in Axillary Apocrine Glands of Patients with Axillary Osmidrosis
Authors: Toyoda Yu , Takada Tappei , Gomi Tsuneaki , Nakagawa Hiroshi , Ishikawa Toshihisa , Suzuki Hiroshi
Published: February 2017

Accumulating evidence suggests that the risk of axillary osmidrosis is governed by a non-synonymous single nucleotide polymorphism (SNP) 538G>A in human ATP-binding cassette C11 (ABCC11) gene. However, little data are available for the expression of ABCC11 protein in human axillary apocrine glands that produce apocrine sweat—a source of odor from the armpits. To determine the effect of the non-synonymous SNP ABCC11 538G>A (G180R) on the ABCC11 in vivo, we generated transiently ABCC11-expressing transgenic mice with adenovirus vector, and examined the protein levels of each ABCC11 in the mice with immunoblotting using an anti-ABCC11 antibody we have generated in the present study. Furthermore, we examined the expression of ABCC11 protein in human axillary apocrine glands extracted from axillary osmidrosis patients carrying each ABCC11 genotype: 538GG, GA, and AA. Analyses of transiently ABCC11-expressing transgenic mice showed that ABCC11 538G>A diminishes the ABCC11 protein levels in vivo. Consistently, ABCC11 protein was detected in the human axillary apocrine glands of the 538GG homozygote or 538GA heterozygote, not in the 538AA homozygote. These findings would contribute to a better understanding of the molecular basis of axillary osmidrosis.
Antimicrobial Treatment of Polymeric Medical Devices by Silver Nanomaterials and Related Technology
Authors: Polívková Markéta , Hubáček Tomáš , Staszek Marek , Švorčík Václav , Siegel Jakub
Published: February 2017

Antimicrobial biocompatible polymers form a group of highly desirable materials in medicinal technology that exhibit interesting thermal and mechanical properties, and high chemical resistance. There are numerous types of polymers with antimicrobial activity or antimicrobial properties conferred through their proper modification. In this review, we focus on the second type of polymers, especially those whose antimicrobial activity is conferred by nanotechnology. Nanotechnology processing is a developing area that exploits the antibacterial effects of broad-scale compounds, both organic and inorganic, to form value-added medical devices. This work gives an overview of nanostructured antimicrobial agents, especially silver ones, used together with biocompatible polymers as effective antimicrobial composites in healthcare. The bactericidal properties of non-conventional antimicrobial agents are compared with those of conventional ones and the advantages and disadvantages are discussed.
Metabolic Effects of Berries with Structurally Diverse Anthocyanins
Authors: Overall John , Bonney Sierra , Wilson Mickey , Beermann Arnold , Grace Mary , Esposito Debora , Lila Mary , Komarnytsky Slavko
Published: February 2017

Overconsumption of energy dense foods and sedentary lifestyle are considered as major causes of obesity-associated insulin resistance and abnormal glucose metabolism. Results from both cohort studies and randomized trials suggested that anthocyanins from berries may lower metabolic risks, however these reports are equivocal. The present study was designed to examine effects of six berries with structurally diverse anthocyanin profiles (normalized to 400 µg/g total anthocyanin content) on development of metabolic risk factors in the C57BL/6 mouse model of polygenic obesity. Diets supplemented with blackberry (mono-glycosylated cyanidins), black raspberry (acylated mono-glycosylated cyanidins), blackcurrant (mono- and di-glycosylated cyanidins and delphinidins), maqui berry (di-glycosylated delphinidins), Concord grape (acylated mono-glycosylated delphinidins and petunidins), and blueberry (mono-glycosylated delphinidins, malvidins, and petunidins) showed a prominent discrepancy between biological activities of delphinidin/malvidin-versus cyanidin-type anthocyanins that could be explained by differences in their structure and metabolism in the gut. Consumption of berries also resulted in a strong shift in the gastrointestinal bacterial communities towards obligate anaerobes that correlated with decrease in the gastrointestinal luminal oxygen and oxidative stress. Further work is needed to understand mechanisms that lead to nearly anoxic conditions in the gut lumens, including the relative contributions of host, diet and/or microbial oxidative activity, and their implication to human health.
Impacts of Dietary Phytochemicals in the Presence and Absence of Pesticides on Longevity of Honey Bees (Apis mellifera)
Authors: Liao Ling-Hsiu , Wu Wen-Yen , Berenbaum May
Published: February 2017

Because certain flavonols and phenolic acids are found in pollen and nectar of most angiosperms, they are routinely ingested by Apis mellifera, the western honey bee. The flavonol quercetin and the phenolic acid p-coumaric acid are known to upregulate detoxification enzymes in adult bees; their presence or absence in the diet may thus affect the toxicity of ingested pesticides. We conducted a series of longevity assays with one-day-old adult workers to test if dietary phytochemicals enhance longevity and pesticide tolerance. One-day-old bees were maintained on sugar syrup with or without casein (a phytochemical-free protein source) in the presence or absence of quercetin and p-coumaric acid as well as in the presence or absence of two pyrethroid insecticides, bifenthrin and β-cyfluthrin. Dietary quercetin (hazard ratio, HR = 0.82), p-coumaric acid (HR = 0.91) and casein (HR = 0.74) were associated with extended lifespan and the two pyrethroid insecticides, 4 ppm bifenthrin (HR = 9.17) and 0.5 ppm β-cyfluthrin (HR = 1.34), reduced lifespan. Dietary quercetin enhanced tolerance of both pyrethroids; p-coumaric acid had a similar effect trend, although of reduced magnitude. Casein in the diet appears to eliminate the life-prolonging effect of p-coumaric acid in the absence of quercetin. Collectively, these assays demonstrate that dietary phytochemicals influence honey bee longevity and pesticide stress; substituting sugar syrups for honey or yeast/soy flour patties may thus have hitherto unrecognized impacts on adult bee health.